Hyperinsulinism-hyperammonemia syndrome in an infant with seizures

Strajnar, A; Tansek, MZ; Podkrajsek, KT; Battelino, T; Groselj, U

doi:10.2478/bjmg-2018-0014

Abstract

Hyperinsulinism-hyperammonemia syndrome (HI/HA) is the second most common form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). The main clinical characteristics of HI/HA syndrome are repeated episodes of symptomatic hypoglycemia, but not usually severe. Consequently, children with HI/HA syndrome are frequently not recognized in the first months of life. An 8-month-old boy was admitted to a hospital due to hypoglycemia seizures. He also had asymptomatic hyperammonemia with no signs of lethargy or headaches. Genetic testing revealed autosomal dominant syndrome, a mutation in the GLUD1 gene (p.Arg274Cys). The boy started treatment with diazoxide. Subsequent growth and neurological development were normal. Hypoglycemic symptoms in HI/HA syndrome may vary from being non specific to severe. As hypoglycemia could lead to brain injury and impairment of neurological development, timely diagnosis and management are essential. If transient hypoglycemia is ruled out, metabolic disorders must be taken into account.

References

Potter M, Hammond JW, Sim KG, Green AK, Wilcken B. Ornithine carbamoyltransferase deficiency: Improved sensitivity of testing for protein tolerance in the diagnosis of heterozygotes. J Inherit Metab Dis. 2001; 24(1): 5-14.
Search in Google Scholar Back to article
Santer R, Kinner M, Passarge M, Superti-Furga A, Mayatepek E, Meissner T, et al. Novel missense mutations outside the allosteric domain of glutamate dehydrogenase are prevalent in European patients with the congenital hyperinsulinism-hyperammonemia syndrome. Hum Genet. 2001; 108(1): 66-71.
Search in Google Scholar Back to article
Sarajlija A, Milenkovic M, Djordjevic K, Mitrovic S, Todorovic B, Kecman Khalid H. Early presentation of hyperinsulinism/hyperammonemia syndrome in three Serbian ptients. J Clin Res Pediatr Endocrinol. 2015; 8(2): 228-231.
Search in Google Scholar Back to article
Stanley CA. Hyperinsulinism in infants and children. Pediatr Clin North Am. 1997; 44(2): 363-374.
Search in Google Scholar Back to article
Senniappan S, Shanti B, James C, Hussain K. Hyperinsulinaemichypoglycaemia: Genetic mechanisms, diagnosis and management. J Inherit Metab Dis. 2012; 35(4): 589-601.
Search in Google Scholar Back to article
Zschocke J, Hoffmann GF. Vademecum Metabolicum. Diagnoses and Treatment of Inborn Errors of Metabolism, 3rd ed. Friedrichsdorf (Hesse, Germany): Schattauer GmbH, 2011.
Search in Google Scholar Back to article
Mathew PM, Young JM, Abu-Osba YK, Mulhern BD, Hammoudi S, Hamdan JA, et al. Persistent neonatal hyperinsulinism. Clin Pediatr (Philadelphia). 1988; 27(3): 148-151.
Search in Google Scholar Back to article
Kapoor RR, Flanagan SE, James C, Shield J, Ellard S, Hussain K. Hyperinsulinaemichypoglycaemia. Arch Dis Child. 2009; 94(6): 450-457.
Search in Google Scholar Back to article
Senniappan S, Arya VB, Hussain K. The molecular mechanisms, diagnosis and management of congenital hyperinsulinism. Indian J Endocrinol Metab. 2013; 17(1): 19-30.
Search in Google Scholar Back to article
Stanley CA. Hyperinsulinism/hyperammonemia syndrome: Insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism. Mol Genet Metab. 2004; 81(1): 45-51.
Search in Google Scholar Back to article
MacMullen C, Fang J, Hsu BY, Kelly A, de Lonlay-Debeney P, Saudubray JM, et al. Hyperinsulin-ism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase. J Clin Endocrinol Metab. 2001; 86(4): 1782-1787.
Search in Google Scholar Back to article
Kelly A, Ng D, Ferry RJ Jr, Grimberg A, Koo-McCoy S, Thornton PS, et al. Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome. J Clin Endocrinol Metab. 2001; 86(8): 3724-3728.
Search in Google Scholar Back to article
Stanley CA, Fang J, Kutyna K, Hsu BY, Ming JE, Glaser B, et al.; HI/HA Contributing Investigators. Molecular basis and characterization of the hyperinsulinism/hyperammonemia syndrome: Predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene. Diabetes. 2000; 49(4): 667-673.
Search in Google Scholar Back to article
Ashcroft FM. ATP-sensitive potassium channelopathies: Focus on insulin secretion. J Clin Invest. 2005; 115(8): 2047-2058.
Search in Google Scholar Back to article
Hsu BYL, Kelly A, Thornton PS, Greenberg CR, Dilling LA, Stanley CA. Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome. J Pediatr. 2001; 138(3): 383-389.
Search in Google Scholar Back to article
Stanley CA, Matschinsky FM. Historical perspective on the genetic forms of congenital hyperinsulinism. In: Stanley CA, De León DD, Eds. Monogenic Hyperinsulinemic Hypoglycemia Disorders. Frontiers in Diabetes, Vol. 21. Basel (Basel-Stadt, Switzerland): S. Karger Ag, 2012: 1-6.
Search in Google Scholar Back to article
Sener A, Malaisse-Lagae F, Malaisse WJ. Stimulation of pancreatic islet metabolism and insulin release by a nonmetabolizable amino acid. Proc Natl Acad Sci USA. 1981; 78(9): 5460-5464 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC348765/).
Search in Google Scholar Back to article
Gao Z, Li G, Najafi H, Wolf BA, Matschinsky FM. Glucose regulation of glutaminolysis and its role in insulin secretion. Diabetes. 1999; 48(8): 1535-1542.
Search in Google Scholar Back to article
Maechler P, Wollheim CB. Mitochondrial glutamate acts as a messenger in glucose-induced insulin exocytosis. Nature. 1999; 402(6762): 685-689.
Search in Google Scholar Back to article
Aoki TT, Muller WA, Brennan MF, Cahill Jr GF. Blood cell and plasma amino acid levels across forearm muscle during a protein meal. Diabetes. 1973; 22(10): 768-775.
Search in Google Scholar Back to article
Flanagan SE, Patch AM, Locke JM, Akcay T, Simsek E, Alaei M, et al. Genome-wide homozygosity analysis reveals HADH mutations as a common cause of diazoxide-responsive hyperinsulinemic-hypoglycemia in consanguineous pedigrees. J Clin Endocrinol Metab. 2011; 96(3): 498-502.
Search in Google Scholar Back to article

Hyperinsulinism-hyperammonemia syndrome in an infant with seizures

Abstract

Paradigm

My account