The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It is an instrument that supports the diagnosis of intellectual and developmental disabilities in patients from birth to 90 years. This test measures the following 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0, 100). The overall DQ score is calculated from the mean age-equivalent score obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills. A positive value indicates improvement in health and cognition.

The FPSS is an MPS III-specific disability assessment that evaluates motor function, expressive language, and cognitive function on a 0- to 3- point scale and can be used for individuals of all ages. A score of 3 points is assigned for normal function, 2 points for beginning of regression, 1 point for severe level of regression, and 0 points for lost skills. The total disability score (TDS) is the average of the motor function, speech, and cognitive function scores (range: 0, 3). The scoring is based on the parent's response to a detailed questionnaire that covers several aspects of the disease. A positive value indicates improvement in function.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).

Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Profound hearing loss: 91+ decibels hearing level (dBHL).

The parent form, CHQ-PF50, is designed to measure the physical and psychosocial well-being of children 5 years and older. In this trial it was used to assess the health of children 5 to 18 years of age. It consists of 13 health concepts including 11 multi-item and 2 single-item scales: physical function, role/social-emotional/behavioral, role/social-physical, bodily pain, general behavior, mental health, self-esteem, general health perceptions, change in health, parental impact-emotional, parental impact-time, family activities, and family cohesion. The parental impact scales capture the amount of emotional distress and time limitation experienced by the parent due to the child's physical health, emotional well-being, attention/learning abilities, ability to get along with others, and general behavior. The Change in Health section assesses changes in health over the previous year.

The ITQoL Questionnaire is a generic, validated health status measure for children aged 2 months up to 5 years, including items and scales to measure aspects of physical functioning, development, pain, mood, behavior, general health, and impact on parents. In this study the ITQoL was also administered to patients who were developmentally functioning at or below the age of years. Growth and development is one of 12 health concepts measured by ITQoL. Transformed scores for all subscales range from 0 to 100, with a higher score indicating better health. A positive value indicates improvement.

The CSHQ is a validated, retrospective, parent-reported sleep screening tool. The questionnaire consists of 35 items that yield a TSD score, as well as 8 subscale scores, including bedtime resistance, sleep duration, parasomnias, sleep disordered breathing, night wakings, daytime sleepiness, sleep anxiety, and sleep onset delay. The questionnaire was designed for children aged 4 to 12 years. Parents were asked to think of a recent "typical" week of their child's sleep and to indicate how often sleep disturbance behaviors occurred. A 3-point scale was used for rating: "usually" if the sleep behavior occurs 5 to 7 times per week, "sometimes" for 2 to 4 times per week, and "rarely" for once or not at all during the week. The TSD score, which is the sum of all responses, included all items of the 8 subscales, but consisted of only 33 items because two on the bedtime resistance and sleep anxiety subscales were identical (range: 0, 99). A negative value indicates less sleep disturbance.

Tau proteins are involved in the building and stabilization of axonal microtubules in the CNS. The phosphorylation of tau proteins associated with microtubules is believed to be involved in destabilizing axons and extensively phosphorylated tau (ptau) has been observed in patients with Alzheimer disease and other neurodegenerative diseases. Because MPS IIIA is a neurodegenerative disease, CSF phosphorylated tau levels were determined to evaluate the potential role of this process in the natural history of the disease. A negative value indicates that phosphorylated tau levels decreased.

Total of all reporting groups

The determination of whether a patient received BSID-III was based on an algorithm that includes the patient's calendar age and VABS-II age -equivalent score (See Outcome 1). The BSID-III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The KABC-II is an individually administered measure of processing and reasoning abilities. The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0, 100). The BSID-III DQ score is based on the cognitive domain. The DQ score for KABC-II is calculated from the average non-verbal age-equivalent score. A positive value indicates improvement in health and cognition.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It is an instrument that supports the diagnosis of intellectual and developmental disabilities in patients from birth to 90 years. This test measures the following 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The mean age-equivalent score is obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills (range: 0, unbound). A positive value indicates improvement in health and cognition

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. It is an instrument that supports the diagnosis of intellectual and developmental disabilities in patients from birth to 90 years. This test measures the following 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0, 100). The overall DQ score is calculated from the mean age-equivalent score obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills. A positive value indicates improvement in health and cognition.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

Urine GAG was measured by a dye binding assay. A negative value indicates that GAG levels decreased.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

Total brain cortical gray matter volume was determined by analysis of brain MRI. The analysis was performed using "Freesurfer" software, which provides completely automated parcellation of the brain cortex and subcortical structures. In some cases, manual adjustments were necessary in cases of intensity normalization failure, resulting in erroneous white matter segmentation. A negative value indicates that gray matter volume decreased.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

The FPSS is an MPS III-specific disability assessment that evaluates motor function, expressive language, and cognitive function on a 0- to 3- point scale and can be used for individuals of all ages. A score of 3 points is assigned for normal function, 2 points for beginning of regression, 1 point for severe level of regression, and 0 points for lost skills. The total disability score (TDS) is the average of the motor function, speech, and cognitive function scores (range: 0, 3). The scoring is based on the parent's response to a detailed questionnaire that covers several aspects of the disease. A positive value indicates improvement in function.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. An abnormal value was greater than 21 decibels hearing level (dBHL).

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Sensorineural hearing loss occurs from damage to the inner ear, the brain, or the nerve that runs from the ear to the brain (auditory nerve). Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Conductive hearing loss occurs when there is a problem conducting sound waves along the route through the outer ear, tympanic membrane, or middle ear. Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (number of neurons firing), latency (speed of transmission), interpeak latency (time between peaks), and interaural latency (difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Mild hearing loss: 21-40 decibels hearing level (dBHL), moderate hearing loss: 41-70 dBHL, severe hearing loss: 71-90 dBHL.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

Hearing loss in subjects with MPS IIIA was characterized by assessing the ABR. The ABR is a voltage response evoked by acoustic stimuli as sound is processed along the auditory pathway. It consists of electrical signals resulting from the sum of sound-evoked activity along the auditory nerve and brainstem nuclei. The ABR analysis determines the sound intensity at which a neural response first appears (hearing threshold). Other parameters of interest include amplitude (the number of neurons firing), latency (the speed of transmission), interpeak latency (the time between peaks), and interaural latency (the difference in wave V latency between ears). The interpeak latency I-V interval (or central transmission time) is considered the most reliable index of brainstem function. Auditory brainstem response assessments were conducted under anesthesia. Profound hearing loss: 91+ decibels hearing level (dBHL).

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

ECG allows a non-invasive assessment of cardiac structure, function, and hemodynamics and can provide essential insight into mechanisms of disease and therapeutic benefit.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

ECG allows a non-invasive assessment of cardiac structure, function, and hemodynamics and can provide essential insight into mechanisms of disease and therapeutic benefit. Regurgitation indicates that blood flows backwards through the valve.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients.

ECG allows a non-invasive assessment of cardiac structure, function, and hemodynamics and can provide essential insight into mechanisms of disease and therapeutic benefit. Backwards blood flow through the tricuspid valve is measured during one heartbeat. A negative value indicates decreased velocity.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

ECG allows a non-invasive assessment of cardiac structure, function, and hemodynamics and can provide essential insight into mechanisms of disease and therapeutic benefit. Blood flow through the mitral valve is measured during one heartbeat.The E/A ratio measures the relationship between early (E) and late (A) inflow velocity by dividing E by A. A positive value indicates that either early flow through the mitral valve (E) increased or late flow through the valve (A) decreased.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

Liver volume was obtained via abdominal MRI. A negative value indicates that volume decreased.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

Spleen volume was assessed via abdominal MRI. A negative value indicates that volume decreased.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

The parent form, CHQ-PF50, is designed to measure the physical and psychosocial well-being of children 5 years and older. In this trial it was used to assess the health of children 5 to 18 years of age. It consists of 13 health concepts including 11 multi-item and 2 single-item scales: physical function, role/social-emotional/behavioral, role/social-physical, bodily pain, general behavior, mental health, self-esteem, general health perceptions, change in health, parental impact-emotional, parental impact-time, family activities, and family cohesion. The parental impact scales capture the amount of emotional distress and time limitation experienced by the parent due to the child's physical health, emotional well-being, attention/learning abilities, ability to get along with others, and general behavior. The Change in Health section assesses changes in health over the previous year.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

The ITQoL Questionnaire is a generic, validated health status measure for children aged 2 months up to 5 years, including items and scales to measure aspects of physical functioning, development, pain, mood, behavior, general health, and impact on parents. In this study the ITQoL was also administered to patients who were developmentally functioning at or below the age of years. Growth and development is one of 12 health concepts measured by ITQoL. Transformed scores for all subscales range from 0 to 100, with a higher score indicating better health. A positive value indicates improvement.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

The CSHQ is a validated, retrospective, parent-reported sleep screening tool. The questionnaire consists of 35 items that yield a TSD score, as well as 8 subscale scores, including bedtime resistance, sleep duration, parasomnias, sleep disordered breathing, night wakings, daytime sleepiness, sleep anxiety, and sleep onset delay. The questionnaire was designed for children aged 4 to 12 years. Parents were asked to think of a recent "typical" week of their child's sleep and to indicate how often sleep disturbance behaviors occurred. A 3-point scale was used for rating: "usually" if the sleep behavior occurs 5 to 7 times per week, "sometimes" for 2 to 4 times per week, and "rarely" for once or not at all during the week. The TSD score, which is the sum of all responses, included all items of the 8 subscales, but consisted of only 33 items because two on the bedtime resistance and sleep anxiety subscales were identical (range: 0, 99). A negative value indicates less sleep disturbance.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

Tau proteins are involved in the building and stabilization of axonal microtubules in the CNS. The phosphorylation of tau proteins associated with microtubules is believed to be involved in destabilizing axons and extensively phosphorylated tau (ptau) has been observed in patients with Alzheimer disease and other neurodegenerative diseases. Because MPS IIIA is a neurodegenerative disease, CSF tau levels were determined to evaluate the potential role of this process in the natural history of the disease. A negative value indicates that total tau levels decreased.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

Tau proteins are involved in the building and stabilization of axonal microtubules in the CNS. The phosphorylation of tau proteins associated with microtubules is believed to be involved in destabilizing axons and extensively phosphorylated tau (ptau) has been observed in patients with Alzheimer disease and other neurodegenerative diseases. Because MPS IIIA is a neurodegenerative disease, CSF phosphorylated tau levels were determined to evaluate the potential role of this process in the natural history of the disease. A negative value indicates that phosphorylated tau levels decreased.

All analyses were based on the Main Analysis Population, which included all enrolled patients. Data were not available for all patients at all time points.

Patients ≥ 6 years of age with MPS IIIA who were untreated with any investigational products (drugs and/or devices).