Strong Genetic

Familial Hyperinsulinism (ABCC8-Related)

GeneABCC8rsIDrs104893896, rs104893897, rs104893898InheritanceAutosomal recessive (diffuse form); autosomal dominant forms also exist but are milderCarrier frequency~1 in 66 Ashkenazi Jewish, rare in general populationSystemCarrier Screening

Summary

Familial hyperinsulinism is a condition where the pancreas secretes too much insulin, causing persistent and potentially dangerous hypoglycaemia (low blood sugar). The ABCC8 gene encodes the sulfonylurea receptor (SUR1), which is part of the ATP-sensitive potassium channel in pancreatic beta cells — the molecular switch that regulates insulin release in response to blood glucose levels. When this channel is defective, beta cells release insulin continuously regardless of blood glucose, driving sugar levels dangerously low.

Practical takeaway

This matters when planning children, particularly if your partner is also of Ashkenazi Jewish descent — where carrier frequency is approximately 1 in 66. A carrier test through a GP or genetic counselling service can determine your partner's status. If you are both carriers, a genetic counsellor can discuss the condition's spectrum, the distinction between focal and diffuse forms, and the treatment options. The key reassurance: focal disease (roughly half of cases) is surgically curable, medical management is available, and neonatal screening awareness enables early intervention. Realised does not calculate reproductive risk or advise on reproductive decisions.

Evidence detail

What Carrier Status Means For You

You are not affected. One working copy of ABCC8 produces functional sulfonylurea receptors and normal insulin regulation. Your blood sugar regulation is entirely normal. Your carrier status becomes relevant if your partner also carries an ABCC8 variant. In that case, each child has a 25% chance of having recessive familial hyperinsulinism, a 50% chance of being an unaffected carrier, and a 25% chance of inheriting neither variant.

Population Context

The F1388del variant is an Ashkenazi Jewish founder mutation, giving this population a carrier frequency of approximately 1 in 66. Familial hyperinsulinism also occurs in other populations — notably in Saudi Arabia and Finland — due to different ABCC8 variants and founder effects. Outside these high-frequency populations, ABCC8-related hyperinsulinism is rare. The condition is the most common cause of persistent hyperinsulinism in infancy. Part of the expanded Ashkenazi Jewish carrier panel.

Limitations

23andMe tests 3 of over 150 known pathogenic ABCC8 variants. For Ashkenazi Jewish individuals, the F1388del variant provides good coverage of the primary founder allele. For non-Ashkenazi individuals, coverage is very limited. Additionally, ABCC8 can cause autosomal dominant mild hyperinsulinism, which is a different clinical entity not well-captured by recessive carrier testing. A "not detected" result reduces but does not eliminate carrier risk. Comprehensive carrier screening through a clinical laboratory covers more variants and is recommended if a partner is a known carrier or if there is family history of neonatal hypoglycaemia.

Sources (5)

Last updated March 2026
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