Congenital Hyperinsulinism

Also known as: Persistent Hyperinsulinaemic Hypoglycaemia of Infancy (PHHI); Nesidioblastosis

Background

Congenital hyperinsulinism (CHI) is a rare inherited disorder in which there is an over production of insulin. Insulin is a hormone that controls the blood glucose (sugar) level. Too much insulin leads to hypoglycaemia (low blood glucose levels).

Credits

Last updated July 2016 by Professor Khalid Hussain, Consultant Paediatric Endocrinologist, Great Ormond Street Hospital and Institute of Child Health, London, UK.

What are the symptoms?

If the hypoglycaemia is not treated it can cause brain damage, learning disability and, in severe cases, death. Neonatal onset CHI shows in the first days or weeks after birth and is the most severe form. Infant onset CHI shows in the first few months, or even years, of life and is milder.

Features of neonatal onset CHI:

  • hunger
  • lethargy (drowsy/tired)
  • seizures
  • apnoea (suspension of breathing)
  • agitation/restlessness
  • pallor (looking pale)
  • poor feeding
  • irritability
  • sweating.

Features of infant onset CH include:

  • any of the above symptoms
  • confusion
  • mood or behaviour changes.

What are the causes?

Overproduction of insulin by the beta cells in the pancreas is the cause of CHI. It is due to a genetic change that means that the amount of insulin produced is not regulated. Insulin removes excess sugars from the blood and converts it into glycogen. A number of gene mutations (changes to DNA) are now known to be involved in CHI. So far, mutations in the following genes have been identified: ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A/1A and UCP2. However, in about 50 per cent of patients the genetic basis of the disease is not known.

How is it diagnosed?

Fast diagnosis of CHI can be made if blood and urine samples are taken while in an episode of hypoglycaemia. Following diagnosis, children should be referred to a specialist centre.

How is it treated?

Treatment of CHI in the short term is by immediate correction of the hypoglycaemia by intravenous glucose to prevent further hypoglycaemia and brain damage. In the longer term, other medications, such as diazoxide, are used. A pancreatectomy (surgery to remove a large or small part of the pancreas) has to be carried out when medication does not maintain proper regulation of the production of insulin.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Autosomal recessive inheritance in the most common form of severe inherited CHI. However, autosomal dominant forms have now also been described. Genetic counselling should be sought in families known to be at risk of CHI.

Prenatal diagnosis
In some forms of CHI, amniocentesis at 15 to 18 weeks of pregnancy may be possible where there is already an affected family member and the mutation causing CHI has been identified. However, this is not possible in all forms of CHI.

Is there support?

Children’s Hyperinsulinism Charity

Email: [email protected]
Website: hyperinsulinism.co.uk

The group is a Registered Charity No. 1165562. They are a UK charity to support families who have children with Congenital Hyperinsulinism by holding conferences, raising awareness and funds for research.

Group details last updated July 2016.

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