Genes : CACNA1D and GLUD1

Also known as Hyperinsulinism-hyperammonemia syndrome, congenital hyperinsulinism (CHI)

OMIM# 114206

OMIM# 138130 138130

1.     The disease

Familial Hyperinsulinemic hypoglycaemia or congenital hyperinsulinism (CHI) is characterized by an excessive or uncontrolled insulin secretion and recurrent episodes of hypoglycaemia that can result in neurological sequelae if left untreated. There are two forms according to the response to first line treatment: diazoxide-sensitive and diazoxide-resistant hyperinsulinism; and three histopathological forms: focal, diffuse, and atypical forms.


2.     The symptoms

Hypoglycaemia that ranges from severe neonatal onset to childhood onset with mild symptoms. Neonatal-onset disease manifests within hours to days after birth. In the newborn period, presenting symptoms may be nonspecific, including seizures, hypotonia, poor feeding, and apnoea. Childhood-onset disease manifests during the first months or years of life and can present with an unprovoked seizure or laboratory evidence of hypoglycaemia noted during acute illness during which nutritional intake is reduced. Some individuals may be asymptomatic. Lack of early signs or symptoms does not exclude the diagnosis.

  • CACNA1D: Characterized by persistent diazoxide-responsive hypoglycaemia, mild aortic insufficiency, severe hypotonia and developmental delay.
  • GLUD1: characterized by an excessive insulin secretion, asymptomatic hyperammonaemia and recurrent episodes of profound hypoglycaemia induced by fasting and protein rich meals.
  1. Actions to take in case of early diagnosis:

  • CHI is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Endocrinology Center. Management is provided by multidisciplinary team.
  • Long-term medical management with a combination of drug therapies. Some individuals respond very well to therapy with diazoxide, somatostatin analogs and glucagon.
  • Genetic counselling should be offered to at-risk family members.


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