# 609968

HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 5; HHF5


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
19p13.2 Hyperinsulinemic hypoglycemia, familial, 5 609968 AD 3 INSR 147670
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal dominant
NEUROLOGIC
Central Nervous System
- Loss of consciousness due to hypoglycemia
- Seizures, hypoglycemic
ENDOCRINE FEATURES
- Hyperinsulinemic hypoglycemia
LABORATORY ABNORMALITIES
- Hypoglycemia, postprandial
- Hyperinsulinemia, fasting
- Elevated serum insulin-to-C-peptide ratio
MISCELLANEOUS
- Genetic heterogeneity (see HHF1 256450)
MOLECULAR BASIS
- Caused by mutation in the insulin receptor gene (INSR, 147670.0037)

TEXT

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).


Clinical Features

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.


Mapping

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.


Inheritance

The transmission pattern of HHF5 in the family reported by Hojlund et al. (2004) was consistent with autosomal dominant inheritance.


Molecular Genetics

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.


REFERENCES

  1. 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, related citations] [Full Text]


Creation Date:
Marla J. F. O'Neill : 3/16/2006
carol : 03/26/2024
carol : 06/02/2016
carol : 6/16/2014
carol : 3/17/2006
carol : 3/16/2006

# 609968

HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 5; HHF5


ORPHA: 263458;   DO: 0070220;  


Phenotype-Gene Relationships

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

TEXT

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).


Clinical Features

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.


Mapping

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.


Inheritance

The transmission pattern of HHF5 in the family reported by Hojlund et al. (2004) was consistent with autosomal dominant inheritance.


Molecular Genetics

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.


REFERENCES

  1. 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]


Creation Date:
Marla J. F. O'Neill : 3/16/2006

Edit History:
carol : 03/26/2024
carol : 06/02/2016
carol : 6/16/2014
carol : 3/17/2006
carol : 3/16/2006