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| ID | Type | Description | Link |
|---|---|---|---|
| AOL | Other Grant/Funding Number | University Hospital Toulouse, local funding 2014 |
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Noonan syndrome (NS) is a rare genetic disease (incidence 1/2500 live births) characterized by the association of craniofacial manifestations, cardiopathies, short stature, and tumor predisposition. The genetic causes of Noonan Syndrome are mutations of genes involved in the Ras/Mitogen-Activated Protein Kinases (MAPK) pathway, mainly the gene encoding the tyrosine phosphatase Shp2 (50% of patients).Shp2 appears to be involved in many facets of energy metabolism control (glucose homeostasis, adipose tissue function…), through mechanisms that are poorly understood. Several metabolic anomalies (reduced adiposity, improved glucose tolerance) have been recently identified in an original mouse model carrying Shp2 mutation. Moreover, recent clinical survey has shown that adult Noonan Syndrome patients are protected from developping overweight and obesity when compared to the general population. However, the metabolic status associated with Noonan Syndrome condition has not been explored to date.
Differential hormone sensitivity is associated with Noonan Syndrome and participates in the development of some symptoms. The investigators have demonstrated that MAPK upregulation in Noonan Syndrome is responsible for partial growth hormone (GH) insensitivity, and subsequent growth retardation.
Clinical traits evocative of energy metabolism dysfunctions have been recently reported in Noonan Syndrome patients, although the origins and consequences of these metabolic changes have not been documented to date. The aim of this study is to explore the metabolic status of children with Noonan Syndrome.
Children with Noonan Syndrome will be compared with age- and sex-matched healthy children. The investigators hypothesize than Noonan Syndrome children have an increased insulin sensitivity compared to GHD children.
Study parameters will be collected including: clinical measurements (height, weight, body mass index, waist circumference, and blood pressure), glucose and insulin levels at baseline and after an oral glucose tolerance test (OGTT), body composition measured by dual-energy x-ray absorptiometry (DXA).
The study will include only one visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Noonan Syndrome Children | Experimental | Children with Noonan Syndrome will be compared with age- and sex-matched healthy children. We hypothesize than Noonan Syndrome children have an increased insulin sensitivity compared to GHD children. Study parameters will be collected including: clinical measurements (height, weight, body mass index, waist circumference, and blood pressure), glucose and insulin levels at baseline and after an oral glucose tolerance test (OGTT), body composition measured by dual-energy x-ray absorptiometry (DXA). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Glucose tolerance test | Other | Oral glucose tolerance test (OGTT): glucose and insulin levels will be measured at time points 0, 90 and 120 min or 30, 60, 90 and 120 after 1.75 g/Kg (max 75 g) glucose administration depending of the patient weight. |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin sensitivity determined from the calculation of the Quantitative insulin sensitivity check index (QUICKI). | Measured at the patient's arrival (TO) from the blood levels of glucose and fasting insulin | T0 on an empty stomach |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin sensitivity determined with HOMA index | Glucose and insulin levels will be measured at time points 0, 90 and 120 min (children weigh 17-25kg) or 30, 60, 90 and 120 min (children weigh >25kg) after 1.75g/kg glucose administration (oral glucose tolerance test) | T30, T60, T90 and T120 minutes after oral glucose tolerance test |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Edouard, MD | CHU Toulouse, Hôpital des Enfants | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Toulouse - Hôpital des Enfants | Toulouse | 31052 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33910978 | Result | Paccoud R, Saint-Laurent C, Piccolo E, Tajan M, Dortignac A, Pereira O, Le Gonidec S, Baba I, Gelineau A, Askia H, Branchereau M, Charpentier J, Personnaz J, Branka S, Auriau J, Deleruyelle S, Canouil M, Beton N, Salles JP, Tauber M, Weill J, Froguel P, Neel BG, Araki T, Heymes C, Burcelin R, Castan I, Valet P, Dray C, Gautier EL, Edouard T, Pradere JP, Yart A. SHP2 drives inflammation-triggered insulin resistance by reshaping tissue macrophage populations. Sci Transl Med. 2021 Apr 28;13(591):eabe2587. doi: 10.1126/scitranslmed.abe2587. Epub 2021 Apr 28. |
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| ID | Term |
|---|---|
| C562515 | Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects |
| D007333 | Insulin Resistance |
| D009634 | Noonan Syndrome |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D005951 | Glucose Tolerance Test |
| ID | Term |
|---|---|
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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| Blood pressure |
These tests will be done on arrival in hospital before the oral glucose tolerance test. Blood pressure is measured after 10 minutes of rest in the elongated child. |
| T0 |
| Blood level of hemoglobin A1c and ghrelin | Blood sample realised at T0 before the oral glucose tolerance test. | T0 on an empty stomach |
| Body composition as fat mass and muscle mass measured by dual-energy x-ray absorptiometry (DXA) | This test will be realised during hospitalisation day, except if it has been done up to 6 months prior to enrollment. | T0 |
| Body mass index | This test will be realised during hospitalisation day, at patient arrival. | T0 |
| Waist circumference | This test will be realised during hospitalisation day, at patient arrival. | T0 |
| Blood level of leptin | Blood sample realised at T0 before the oral glucose tolerance test. | T0 on an empty stomach |
| Blood level of ghrelin | Blood sample realised at T0 before the oral glucose tolerance test. | T0 on an empty stomach |
| D019465 | Craniofacial Abnormalities |
| D009139 | Musculoskeletal Abnormalities |
| D009140 | Musculoskeletal Diseases |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D003933 | Diagnosis |
| D003940 | Diagnostic Techniques, Endocrine |
| D008919 | Investigative Techniques |