GLUD 1 MUTATION CAUSING NON KETOTIC HYPOGLYCEMIA WITH CONCOMITANT HYPERAMMONAEMIA

A CASE REPORT

Abstract

INTRODUCTION
Hypoglycemia is a medical emergency which carries serious short term and long-term consequences. The time of crisis is the best time to collect critical samplings to make the diagnosis. In hyperinsulinaemic hypoglycemia (HH) due to the inhibitory effect of insulin on lipolysis and ketogenesis, there is suppressed ketone body formation, leading to increased risk of hypoglycemic brain injury. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) that are involved in the regulation of pancreatic beta cells have been described to be responsible for the underlying molecular mechanism leading to congenital HH.

CASE
A 10-year-old girl, presented at 4 months old with afebrile seizures. Noted recurrent hypoglycemia needing glucose infusion up to 15 mg/kg/min. Born premature at 34 weeks, birthweight 2.2 kg with no postnatal complications. Physical examinations were unremarkable. Critical sampling done during hypoglycemia; RBS: 1.8 mmol/L, insulin 5.67 uIU/mL (<1), C-peptide 632 ng/mL (0.9-7.1), lactate 6.57 mmol/L (0.63-2.4), ammonia 266.9 umol/L (14.7-55.3), growth hormone 11.3 ng/ml (>10), cortisol 351 nmol/L (>250). Normal LFT and VBG. She was started on oral Diazoxide and hydrochlorothiazide and responded well. Genetic study confirmed heterozygous for a novel missense mutation, G446V, in exon 12 of the GLUD1 gene. Trial of stopping Diazoxide at 9-year-old failed. Hyperinsulinaemia-hyperammonaemia (HI/HA) is the second most common cause of hyperinsulinaemic hypoglycemia. It is caused by mutation in GLUD1 gene resulting in a decreased inhibitory effect of guanosine triphosphate on the glutamate dehydrogenase (GDH) enzyme. HI/HA syndrome patients are Diazoxide responsive and in some cases dietary protein restriction might be necessary.

CONCLUSION
The importance of establishing the correct diagnosis in hyperinsulinism from critical samplings results and genetic study is of importance to predict the prognosis and proper counselling to patient and family.