GTR Home > Conditions/Phenotypes > Persistent hyperinsulinemic hypoglycemia of infancy

Disease characteristics

Excerpted from the GeneReview: Familial Hyperinsulinism
Familial hyperinsulinism (referred to as FHI in this GeneReview) is characterized by hypoglycemia that ranges from severe neonatal-onset, difficult-to-manage disease to childhood-onset disease with mild symptoms and difficult-to-diagnose hypoglycemia. Neonatal-onset disease manifests within hours to two days after birth. Childhood-onset disease manifests during the first months or years of life. In the newborn period, presenting symptoms may be nonspecific, including seizures, hypotonia, poor feeding, and apnea. In severe cases, serum glucose concentrations are typically extremely low and thus easily recognized, whereas in milder cases, variable and mild hypoglycemia may make the diagnosis more difficult. Even within the same family, disease manifestations can range from mild to severe. Individuals with autosomal recessive familial hyperinsulinism, caused by mutations in either ABCC8 or KCNJ11 (FHI-KATP), tend to be large for gestational age and usually present with severe refractory hypoglycemia in the first 48 hours of life; affected infants usually respond only partially to diet or medical management (i.e., diazoxide therapy) and thus may require pancreatic resection. Individuals with autosomal dominant FHI-KATP tend to be appropriate for gestational age at birth, to present at approximately age one year (range: 2 days - 30 years), and to respond to diet and diazoxide therapy. Exceptions to both of these generalities have been reported. FHI-GCK, caused by mutations in GCK, may be much milder than FHI-KATP; however, some persons have severe, diazoxide-unresponsive hypoglycemia. FHI-HADH, caused by mutations in HADH, tends to be relatively mild, although severe cases have been reported. Individuals with FHI-HNF4A, caused by mutations in HNF4A, are typically born large for gestational age and have mild features that respond to diazoxide treatment. FHI-UCP2, caused by mutations in UCP2, is a rare cause of diazoxide-responsive FH1. Hyperammonemia/hyperinsulinism (HA/HI) is associated with mild-to-moderate hyperammonemia and with relatively mild, late-onset hypoglycemia; most but not all affected individuals have mutations in GLUD1.

Associated genes

  • Also known as: ABC36, HHF1, HI, HRINS, MRP8, PHHI, SUR, SUR1, SUR1delta2, TNDM2, ABCC8
    Summary: ATP-binding cassette, sub-family C (CFTR/MRP), member 8

Clinical features

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  • Large for gestational age
  • Intellectual disability
  • Hyperinsulinemic hypoglycemia
  • Hypoglycemic coma
  • Hypoglycemia
  • Hypoglycemic seizures
  • Pancreatic islet-cell hyperplasia
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