| #609975 | ||||||||||||||||||
| HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 4; HHF4 | ||||||||||||||||||
| Phenotype Gene Relationships | ||||||||||||||||||
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| Phenotypic Series | ||||||||||||||||||
| Clinical Synopsis | ||||||||||||||||||
| TEXT | ||||||||||||||||||
| A number sign (#) is used with this entry because familial hyperinsulinemic hypoglycemia-4 is caused by mutation in the gene encoding 3-hydroxyacyl-CoA dehydrogenase (HADH; 601609). For a phenotypic description and discussion of genetic heterogeneity of familial hyperinsulinemic hypoglycemia, see HHF1 (256450). | ||||||||||||||||||
| Clinical Features | ||||||||||||||||||
| Gotlin and Silver (1970) reported a male infant who had profound hypoglycemia at birth, with abnormally high insulin/glucose ratios. Attempts to control his hypoglycemia with conventional dietary and drug management were only partially successful. At 10 months of age he had a prolonged hypoglycemic convulsion resulting in coma, at which time severe hyperinsulinism was confirmed. He underwent partial pancreatectomy; microscopically there was a marked decrease in the secretory granules of the beta cells and an absence of alpha cells. Vidnes (1976) was the first to document glucagon deficiency in a case of persistent hereditary neonatal hypoglycemia. Vidnes and Oyasaeter (1977) described an inbred Pakistani family in which 2 brothers and a sister appear to have had hypoglycemia due to isolated glucagon deficiency. Two of the 3 had died before the nature of the problem was identified. Treatment with glucagon replacement was successful. Molven et al. (2002) restudied the family described by Vidnes and Oyasaeter (1977). Another affected sib, a sister 19 years old at the time of the report, had hypoglycemia, but had been diagnosed with hyperinsulinism. Indeed, Molven et al. (2002) questioned the existence of congenital glucagon deficiency in this family. They concluded that the family had hereditary hyperinsulinism. Clayton et al. (2001) reported an Indian child who presented at age 4 months with a hypoglycemic convulsion. She continued to have frequent episodes of hypoketotic hypoglycemia associated with increased plasma insulin levels. Biochemical studies indicated increased blood acylcarnitine levels, suggesting a disorder of fatty acid oxidation. | ||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||
| In a 4-month-old Indian girl with hyperinsulinemic hypoglycemia, Clayton et al. (2001) identified homozygosity for a mutation in the HADH gene (601609.0003); her apparently nonconsanguineous parents were heterozygous for the mutation. In 4 sibs with hyperinsulinemic hypoglycemia from a consanguineous Pakistani family originally reported by Vidnes and Oyasaeter (1977), Molven et al. (2004) identified homozygosity for a deletion in the HADH gene (601609.0004). The parents were heterozygous for the mutation. | ||||||||||||||||||
| REFERENCES | ||||||||||||||||||
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