ORPHA: 263458; DO: 0070220;
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
---|---|---|---|---|---|---|
19p13.2 | Hyperinsulinemic hypoglycemia, familial, 5 | 609968 | Autosomal dominant | 3 | INSR | 147670 |
A number sign (#) is used with this entry because of evidence that familial hyperinsulinemic hypoglycemia-5 (HHF5) is caused by heterozygous mutation in the insulin receptor gene (INSR; 147670) on chromosome 19p13.
For a phenotypic description and a discussion of genetic heterogeneity of familial hyperinsulinemic hypoglycemia, see HHF1 (256450).
Hojlund et al. (2004) described a large 3-generation Danish family in which affected members had postprandial episodes of neuroglycopenia. The proband was a 21-year-old woman who since the age of 12 had experienced episodes of blurred vision, loss of consciousness, and seizures, occurring 2 to 5 hours after eating, often in conjunction with exercise and relieved by food ingestion. Her EEG was normal. At age 20, hyperinsulinemic hypoglycemia was documented; the patient was noted to be nonobese with no signs of insulin resistance such as skin pigmentation or hirsutism. Nine other family members in 3 generations also had episodes of hypoglycemia which ranged from moderate symptoms of hypoglycemia in 2 family members to episodes with loss of consciousness in 8 and seizures causing admission to emergency units in 5. The reported age of onset was between 3 and 30 years, and all affected family members were shown to have fasting hyperinsulinemia and an elevated serum insulin-to-C-peptide ratio. The proband's sister, who had moderate symptoms of hypoglycemia, showed mild skin pigmentation in the axillae, increased total and free serum levels of testosterone, and polycystic ovaries.
By linkage analysis using DNA from 19 members of a 3-generation Danish family with hyperinsulinemic hypoglycemia, Hojlund et al. (2004) found complete cosegregation of the disease phenotype with a specific haplotype in the insulin receptor region on 19p13. A maximum lod score of 3.21 was achieved.
The transmission pattern of HHF5 in the family reported by Hojlund et al. (2004) was consistent with autosomal dominant inheritance.
In all affected members of a 3-generation Danish family with hyperinsulinemic hypoglycemia, Hojlund et al. (2004) identified heterozygosity for a point mutation in the insulin receptor gene (147670.0030). The mutation was not found in any unaffected family members.
Hojlund, K., Hansen, T., Lajer, M., Henriksen, J. E., Levin, K., Lindholm, J., Pedersen, O., Bech-Nielsen, H. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. Diabetes 53: 1592-1593, 2004. [PubMed: 15161766] [Full Text: https://doi.org/10.2337/diabetes.53.6.1592]