Strong Genetic

Niemann-Pick Disease Type A

Name: Niemann-Pick Disease Type A
Creator: Realised
Published: 2026-03-01

GeneSMPD1rsIDrs120074119, rs120074120, rs120074117InheritanceAutosomal recessiveCarrier frequency~1 in 80 Ashkenazi Jewish, rare in general populationSystemCarrier Screening

Summary

Niemann-Pick disease Type A is a lysosomal storage disorder caused by severe deficiency of the enzyme acid sphingomyelinase. Without this enzyme, sphingomyelin — a fat that is a normal component of cell membranes — accumulates in cells throughout the body, particularly in the brain, liver, spleen, and lungs.

Practical takeaway

This matters when planning children, particularly if your partner is also of Ashkenazi Jewish descent — where carrier frequency is approximately 1 in 80. A carrier test through a GP or genetic counselling service can determine your partner's status. If both parents carry SMPD1 variants, a genetic counsellor can discuss the likely clinical outcome based on which specific variants are involved (Type A vs Type B is determined by the residual enzyme activity of each variant combination). This conversation is best had before pregnancy. 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 SMPD1 produces sufficient acid sphingomyelinase for normal sphingomyelin metabolism. Your carrier status becomes relevant if your partner also carries an SMPD1 variant. In that case, each child has a 25% chance of being affected (the specific combination of variants determines whether the outcome would be Type A or Type B), a 50% chance of being an unaffected carrier, and a 25% chance of inheriting neither variant.

Population Context

Niemann-Pick Type A carrier frequency is highest in the Ashkenazi Jewish population (~1 in 80), where three specific variants (R496L, L302P, fsP330) account for the vast majority of disease alleles. The condition is much rarer in other populations. Niemann-Pick disease is part of the standard Ashkenazi Jewish carrier panel. The condition is named after Albert Niemann and Ludwig Pick, who first described it in the early 20th century.

Limitations

23andMe tests 3 of over 180 known pathogenic SMPD1 variants. For Ashkenazi Jewish individuals, these three variants provide good coverage of the most common disease alleles in this population. For non-Ashkenazi individuals, coverage is substantially lower — many pathogenic variants are private or population-specific. A "not detected" result reduces but does not eliminate carrier risk, particularly in non-Ashkenazi populations. Comprehensive carrier screening through a clinical laboratory covers more variants and can distinguish between variants associated with Type A versus Type B disease.

Sources (5)

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