Strong Genetic

Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)

Name: Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
Creator: Realised
Published: 2026-03-01

GeneACADMrsIDrs77931234, rs121434274, rs77931234, rs121434275InheritanceAutosomal recessiveCarrier frequency~1 in 40-60 Northern EuropeansSystemCarrier Screening

Summary

MCAD deficiency is a fatty acid oxidation disorder where the body cannot efficiently break down medium-chain fatty acids for energy. This matters most during fasting or illness — situations where the body would normally switch from using glucose to burning fat for fuel. Without functioning MCAD enzyme, this switch fails, leading to dangerous hypoglycaemia and accumulation of toxic metabolic intermediates.

Practical takeaway

This matters when planning children. The K329E variant is common in Northern European populations — if your partner shares this ancestry, carrier testing through a GP or genetic counselling service is straightforward. If both parents are carriers, the most important reassurance is that newborn screening catches MCADD at birth, and management is simple and highly effective. A genetic counsellor can walk through what this means in practice. 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 ACADM produces enough enzyme for entirely normal fatty acid metabolism — you process fats normally during fasting and illness. Your carrier status becomes relevant if your partner also carries an ACADM variant. In that case, each child has a 25% chance of having MCADD, a 50% chance of being an unaffected carrier, and a 25% chance of inheriting neither variant.

Population Context

MCADD carrier rates are highest in Northern European populations, particularly those of Dutch, English, and German descent. The K329E variant (historically called K304E before renumbering) accounts for approximately 80% of European MCADD alleles, making it one of the most common inborn errors of metabolism in these populations. The condition is rarer in Southern European, Asian, and African populations. Newborn screening programs have dramatically changed the natural history of MCADD — the condition went from being a leading cause of sudden infant death to a manageable finding identified in the first days of life.

Limitations

23andMe tests 4 of over 80 known pathogenic ACADM variants. The K329E variant alone accounts for ~80% of European alleles, so coverage is reasonably good for Northern European populations. However, rarer variants — particularly those more common in non-European populations — may be missed. A "not detected" result reduces but does not eliminate carrier risk. Comprehensive carrier screening through a clinical laboratory covers more variants and provides higher sensitivity, particularly for individuals of non-Northern European ancestry.

Sources (6)

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