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| Name | Class |
|---|---|
| Universidad Autonoma de Madrid | OTHER |
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Malignant hyperthermia (MH) is a pharmacogenetic disease that manifests itself as a hypermetabolic response of skeletal musculature, in genetically susceptible patients, with the inhalation of volatile halogenated anesthetics, depolarizing neuromuscular relaxants such and, rarely, physical stressors such as intense exercise and heat stroke.
HM diagnosis is based on the performance of two tests:
It also has been described that B lymphocytes of patients with MH have metabolic alterations.
The main objective is to evaluate the association of disorders that occur with hypermetabolic response of skeletal musculature and susceptibility to malignant hyperthermia (MH).
Malignant hyperthermia (MH) is a pharmacogenetic disease that manifests itself as a hypermetabolic response of skeletal musculature, in genetically susceptible patients, with the inhalation of volatile halogenated anesthetics, depolarizing neuromuscular relaxants such and, rarely, physical stressors such as intense exercise and heat stroke.
Risk factors to present this disease are:
There are also other infrequent diseases in which there is a ryanodine canalopathy by a mechanism similar to that seen in MH, but in cells of tissues other than skeletal striated muscle; as well as some drugs and other rare diseases that may be related to MH.
Despite the rarity of MH and given the severity of the disease clinic, it is mandatory to explore possible risks in patients with hypermetabolic response of skeletal musculature due to rare or trigger diseases (medications, drugs of abuse, exercise, extreme heat, others) whose MH risk is not defined.
Although the standard method for the diagnosis of MH is the in vitro test for halothane caffeine contraction (IVCT), it has been described that B lymphocytes of patients with MH have metabolic alterations. Alto, there are about 50 genetic variants associated with MH that have been described.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Population in risk of MH | Patient with hypermetabolic response of skeletal musculature by causes related with Malignant Hyperthermia in the literature. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| In vitro contracture test (IVCT) | Diagnostic Test | In vitro study of muscle contraction after exposure to different substances (caffeine and halothane). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Determination, by an in vitro study of muscular contraction, measuring the muscle tension, of the presence of Malignant Hyperthermia susceptibility in patients with a history of hypermetabolic response of skeletal musculature. | Measured by the tension induced by the muscular contraction in response to the presence of caffeine and halothane. | 5 years |
| Determination, by genetic study, of the presence of susceptibility to Malignant Hyperthermia in patients with a history of hypermetabolic response of skeletal musculature. | Identifying determined genes related with Malignant Hyperthermia risk. | 5 years |
| Study of the concordance of the genetic study and IVCT versus the hypermetabolic response of B lymphocyte, in patients with a history of hypermetabolic response of skeletal musculature. | Extracellular acidification curve in B lymphocytes in response to the agonist RyR1 and 4-CmC. | 5 years |
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Inclusion Criteria:
Exclusion Criteria:
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Patient with hypermetabolic response of skeletal musculature by related causes in the literature with Malignant Hyperthermia.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Elena Ramírez García | Contact | +34 917277559 | elena.ramirezg@uam.es |
| Name | Affiliation | Role |
|---|---|---|
| Elena Ramírez García | Clinical Pharmacology Department, La Paz University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario La Paz | Recruiting | Madrid | 28046 | Spain |
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| ID | Term |
|---|---|
| D008305 | Malignant Hyperthermia |
| ID | Term |
|---|---|
| D007431 | Intraoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011183 | Postoperative Complications |
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| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
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50 variants have been described that can be considered "diagnostic mutations" of RYR1 and CACNA1S, and other under study.
| In vitro test of hypermetabolism in B lymphocytes | Diagnostic Test | In vitro study of the activation of lymphocytes B after being incubated with a cocktail of primary antibodies and measuring the acidification in response to the RyR1, 4-CmC agonist, using ryanodine as a positive control. |
|
| Genetic test | Diagnostic Test | Analysis of genes related to MH (CACNA1S and RYR1). |
|
| D000084462 | Hyperthermia |
| D001832 | Body Temperature Changes |
| D012816 | Signs and Symptoms |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |