| Causes of congenital hyperinsulinism . | Basis of disease . | Disease characteristics . | Age group . | Mode of inheritance . |
|---|---|---|---|---|
Mutation in ABCC8 encoding for SUR1 (OMIM 256450, HHF1) chr 11p15.1 | DIFFUSE defect in β cell membrane KATP channel throughout the pancreas FOCAL Paternal inherited defect with maternal gene silenced leading to focal area of islet clonal expansion | Severe hypoglycaemia, variable, usually poor response to diazoxide | Neonatal–infant | Usually autosomal recessive, homozygous or compound heterozygous; de novo mutation or autosomal dominant Sporadic |
Loss of function mutation in KCNJ11 encoding for Kir6.2 (OMIM 601820, HHF2), chr 11p15.1 | Defect in β-cell membrane KATP channel | Severe hypoglycaemia, variable, usually poor response to diazoxide | Neonatal–infant | Usually autosomal recessive, homozygous or compound heterozygous |
Gain of function mutation in glucokinase (GK) gene encoding for the enzyme glucokinase (OMIM 602485, HHF3), chr 7p15-p13. | Defect in rate-limiting step of β-cell glucose metabolism | Diazoxide responsive, variable severity | Variable age of onset from neonatal onwards | Autosomal dominant |
Loss of function mutation in the HADHSC gene encoding short chain 3-hydroxylacyl-CoA dehydrogenase (SCHAD) (OMIM 609975, HHF4), chr 4q22-q26. | Defect in mitochondrial fatty acid oxidation | Diazoxide responsive | Neonatal-infant | Autosomal recessive |
Mutation in INS, INSB encoding for the insulin receptor (OMIM 609968, HHF5) chr 19p13.2 | Reported from 3 years of age onwards | Autosomal dominant | ||
Gain of function mutation in glutamate dehydrogenase (GLUD1) gene (hyperinsulinaemia and hyperammonaemia, HI/HA) (OMIM 606762, HHF6) chr10q23.3. | Loss of inhibition of glutamate dehydogenase by GTP (and ATP) and uninhibited protein (leucine) stimulated insulin release | Diazoxide responsive | Infant | Autosomal dominant or de novo |
Congenital disorders of glycosylation (CDG) (genetically heterogeneous) | A range of disorders of glycosylation, basis of hypoglycaemia not known | Diazoxide responsive | Infant–toddler | Autosomal recessive |
Mutation in HNF4α gene | Diazoxide responsive, hypoglycaemia often mild or transient in infant progressing to diabetes in adolescence (MODY1), family history of diabetes | Infant | Autosomal dominant | |
Usher syndrome type 1C (OMIM 276904) chr 11p15.1. | Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 | Severe hypoglycaemia, diazoxide insensitive, sensorineural deafness, pigmentary retinopathy | Infant | Autosomal recessive |
| Causes of congenital hyperinsulinism . | Basis of disease . | Disease characteristics . | Age group . | Mode of inheritance . |
|---|---|---|---|---|
Mutation in ABCC8 encoding for SUR1 (OMIM 256450, HHF1) chr 11p15.1 | DIFFUSE defect in β cell membrane KATP channel throughout the pancreas FOCAL Paternal inherited defect with maternal gene silenced leading to focal area of islet clonal expansion | Severe hypoglycaemia, variable, usually poor response to diazoxide | Neonatal–infant | Usually autosomal recessive, homozygous or compound heterozygous; de novo mutation or autosomal dominant Sporadic |
Loss of function mutation in KCNJ11 encoding for Kir6.2 (OMIM 601820, HHF2), chr 11p15.1 | Defect in β-cell membrane KATP channel | Severe hypoglycaemia, variable, usually poor response to diazoxide | Neonatal–infant | Usually autosomal recessive, homozygous or compound heterozygous |
Gain of function mutation in glucokinase (GK) gene encoding for the enzyme glucokinase (OMIM 602485, HHF3), chr 7p15-p13. | Defect in rate-limiting step of β-cell glucose metabolism | Diazoxide responsive, variable severity | Variable age of onset from neonatal onwards | Autosomal dominant |
Loss of function mutation in the HADHSC gene encoding short chain 3-hydroxylacyl-CoA dehydrogenase (SCHAD) (OMIM 609975, HHF4), chr 4q22-q26. | Defect in mitochondrial fatty acid oxidation | Diazoxide responsive | Neonatal-infant | Autosomal recessive |
Mutation in INS, INSB encoding for the insulin receptor (OMIM 609968, HHF5) chr 19p13.2 | Reported from 3 years of age onwards | Autosomal dominant | ||
Gain of function mutation in glutamate dehydrogenase (GLUD1) gene (hyperinsulinaemia and hyperammonaemia, HI/HA) (OMIM 606762, HHF6) chr10q23.3. | Loss of inhibition of glutamate dehydogenase by GTP (and ATP) and uninhibited protein (leucine) stimulated insulin release | Diazoxide responsive | Infant | Autosomal dominant or de novo |
Congenital disorders of glycosylation (CDG) (genetically heterogeneous) | A range of disorders of glycosylation, basis of hypoglycaemia not known | Diazoxide responsive | Infant–toddler | Autosomal recessive |
Mutation in HNF4α gene | Diazoxide responsive, hypoglycaemia often mild or transient in infant progressing to diabetes in adolescence (MODY1), family history of diabetes | Infant | Autosomal dominant | |
Usher syndrome type 1C (OMIM 276904) chr 11p15.1. | Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 | Severe hypoglycaemia, diazoxide insensitive, sensorineural deafness, pigmentary retinopathy | Infant | Autosomal recessive |
This PDF is available to Subscribers Only
View Article Abstract & Purchase OptionsFor full access to this pdf, sign in to an existing account, or purchase an annual subscription.
