Congenital hyperinsulinism (CHI)

Insulin, released by beta-cells in the pancreas, controls blood glucose. Normally the cells release more insulin when glucose is high and switch off when it is low. In CHI the beta-cells release insulin inappropriately all the time and secretion is not regulated by the glucose level. The action of insulin causes hyperinsulinaemic hypoglycaemia. Unlike ordinary low blood sugar, episodes in CHI can occur after eating as well as after fasting or exercise.

High insulin levels also stop the body making ketone bodies, which the brain normally uses as a back-up fuel. A baby with CHI is therefore entirely dependent on circulating glucose to keep the brain working, which is why keeping glucose steady matters so much.

GOSH describes up to 14 known genetic causes. Changes in ABCC8 and KCNJ11 are the most common causes of severe CHI, and MedlinePlus reports ABCC8 in about 40 per cent of cases, while in about half of people the cause is unknown. Inheritance can be autosomal recessive, with a 25% chance for each pregnancy of two carrier parents, or autosomal dominant, with a 50% chance a child inherits it from an affected parent, and some cases arise as new changes.

Other hyperinsulinism is transient, with insulin production high only for a short time, and some syndromes include it. In Beckwith-Wiedemann syndrome, GOSH reports that up to 50 per cent have been observed to develop hyperinsulinaemic hypoglycaemia, and Turner and Kabuki syndromes are other examples.

The two main forms of persistent CHI are focal and diffuse. In focal CHI a small area of the pancreas is affected. Lesions are typically only 2 to 10 mm across and, per GOSH, around 40 to 50 per cent of infants with persistent CHI have this form. In diffuse CHI the whole pancreas is affected, and it can be inherited in a recessive or dominant way or occur sporadically.

Management differs. Focal disease can now be cured if the lesion is accurately located and fully removed. Diffuse disease may need removal of almost the entire pancreas if medicines do not control it.

Symptoms usually begin within the first days of life, though occasionally later in infancy. They include floppiness, shakiness, poor feeding and sleepiness. Seizures can occur, and if low glucose is not corrected the child may lose consciousness, with a risk of brain injury. MedlinePlus reports that about 60 per cent of infants with the condition have a hypoglycaemic episode within the first month and that repeated episodes can lead to seizures, intellectual disability, vision loss and brain damage.

Any baby with unexplained low glucose that needs repeated glucose treatment, or needs high glucose infusion rates, should be assessed for CHI by a specialist team.

Ideally children with suspected CHI are transferred to one of the two UK specialist centres, which have the expertise for detailed, repeated glucose monitoring. During transfer, glucose is kept near normal with a drip or injection. At the centre the first task is stabilisation with intravenous glucose, sometimes through a central venous line, and sometimes a high-carbohydrate feed. Once stable, detailed blood and urine tests taken while glucose is low confirm or exclude CHI, and if needed a supervised diagnostic fast is carried out.

Medicines to reduce insulin release are tried in turn. They include diazoxide, chlorothiazide, nifedipine (rarely used as it is less effective), glucagon and octreotide. Blood samples are sent for genetic analysis, which helps decide whether an 18F-DOPA PET scan is needed to find a focal lesion.

If medicines do not keep glucose safe, surgery is considered. For a focal lesion, removing the affected area often offers a cure. For diffuse disease, removal of most of the pancreas is only an option if medical treatment fails and carries a greater risk of diabetes or pancreatic insufficiency, and hypoglycaemia can still occur afterwards, often in a milder form.

Many children with CHI have feeding problems affecting movement of food through the gut and reflux. A nasogastric tube is sometimes used and, if needed long term, a gastrostomy. GOSH stresses continuing small oral feeds so a child does not lose the desire to eat, with help from speech and language specialists.

Once CHI is stable a degree of normal life can be achieved. Some children have issues with memory and processing information and may need extra support at school and later at work. After pancreatic surgery, insulin-dependent diabetes may develop and many children cope well with treatment and have a near-normal childhood. Pancreatic insufficiency can be treated with enzyme capsules taken with meals.

Before discharge the team teaches parents to monitor glucose, give medicines and follow a written plan for a hypoglycaemic episode, with regular follow-up at the specialist centre and local services involved. Telephone support remains available from the centre. Parent support groups exist for families.

Call 999 for a seizure, loss of consciousness, or a baby who cannot be woken or is very floppy. Follow the written hypoglycaemia plan first, giving glucose as taught, and contact the specialist centre for any glucose that stays low or for vomiting that stops feeds.