GLUD1 (Hyperinsulinism-Hyperammonemia Syndrome, Congenital Hyperinsulinism)
One cause of Congenital Hyperinsulinism (CH) is a mutation
of the GLUD1 gene, which results in hyperinsulinism, hypoglycemia and hyperammonemia.
PrintOne cause of Congenital Hyperinsulinism (CH) is a mutation
of the GLUD1 gene, which results in hyperinsulinism, hypoglycemia and hyperammonemia.
In this Hyperinsulinism-Hyperammonemia Syndrome (HHS), hyperinsulinism may be the only symptom that appears during the neonatal period. Other symptoms include mild, late-onset hypoglycemia which may cause brain damage if not corrected, plasma concentrations that are three to eight times higher than normal, and high levels of ammonia in the blood. HHS occurs in males and females, with wide ethnic distribution with varying phenotypes. Mutations in the GLUD1 gene account for 5% of CH and 80% of HHS. Mutations are autosomal dominant, and de novo in 80% of cases. HHS can be diagnosed by enzymatic activity, however gene sequencing allows for confirmation of diagnosis and genotype/phenotype correlation allows for proper treatment and better surveillance in an affected individuals. Carrier status, prenatal and known familial mutation testing is also available.
One cause of Congenital Hyperinsulinism (CH) is mutation of the GLUD1 gene, which results in hyperinsulinism, hypoglycemia and hyperammonemia. In this Hyperinsulinism-Hyperammonemia Syndrome (HHS), hyperinsulinism may be the only symptom that appears during the neonatal period. Other symptoms include mild, late-onset hypoglycemia which may cause brain damage if not corrected, plasma concentrations that are three to eight times higher than normal, and high levels of ammonia in the blood. HHS occurs in males and females, with wide ethnic distribution with varying phenotypes. Mutations in the GLUD1 gene account for 5% of CH and 80% of HHS. Mutations are autosomal dominant, and de novo in 80% of cases. HHS can be diagnosed by enzymatic activity, however gene sequencing allows for confirmation of diagnosis and genotype/phenotype correlation allows for proper treatment and better surveillance in an affected individuals.
gene sequencing allows for confirmation of diagnosis and genotype/phenotype correlation allows for proper treatment and better surveillance in an affected individuals. Carrier status, prenatal and known familial mutation testing is also available.
The Ambry Test:GLUD1 includes sequencing of exons 1-13 plus at least 20 bases into the 5' and 3' ends of all the introns of the GLUD1 gene. If full gene sequence analysis is requested polymerase chain reaction (PCR) is used to selectively amplify regions of gDNA corresponding to the GLUD1 gene followed by double stranded sequencing in sense and antisense directions to detect sequence variations. If specific mutation analysis is requested, only specific region(s) of DNA is (are) amplified by PCR and sequenced.
The Ambry Test: GLUD1 is designed and validated to be capable of detecting >99% of described mutations in GLUD1.
Blood Samples:
Container: Purple top EDTA tube (preferred) or yellow top citric acetate tube.
Amount: Adult 3-5 cc, pediatric 2 cc minimum.
Storage: 2-8°C. Do not freeze.
Shipment: Room temperature for two-day delivery.
Transfusion Patients: Wait at least two weeks after a packed cell or platelet transfusion and at least four weeks after a whole blood transfusion prior to blood draw.
DNA:
Container: Sterile plastic tube.
Amount: min. 20 μg of DNA in TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 200 μl at ~100 ng/μl.
For specific mutation(s) analysis: min. 5 μg of DNA (~100 ng/μl conc.).
Please provide DNA OD 260-280 ratio (preferred 1.7-1.9) and send agarose picture with high mw genomic DNA, if available.
Storage: -20°C.
Shipment: Shipment frozen on dry ice is preferred, or ship on ice.
For Transfusion Patients: Wait at least two weeks after a packed cell or platelet transfusion and at least four weeks after a whole blood transfusion prior to blood draw.
Blood Spots:
Container: Schleicher + Schuell (S&S) 903 specimen collection paper.
Amount: Minimum of one complete spot of approximately 0.5 inch in diameter.
Storage: Room temperature in a sterile bag.
Shipment: 2-8°C up to 72 hours. Do not freeze.
Saliva:
Container: Oragene DNA Self Collection container.
Amount: 2 ml.
Storage: At room temperature in sterile bag.
Shipment: Ship room temperature for two-day delivery
Prenatal:
Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 1370 | GLUD1 Gene Sequence Analysis | 83891x1, 83894x13, 83898x12, 83904x24, 83909x24, 83912x1 |
| Technique | Days |
|---|---|
| GLUD1 Gene Sequence Analysis | 10-21 |
References available upon request.