Zellweger Spectrum Disorder, PEX1-Related
Summary
Zellweger spectrum disorder (ZSD) is a continuum of peroxisome biogenesis disorders ranging from severe (classic Zellweger syndrome) to mild (infantile Refsum disease / neonatal adrenoleukodystrophy). PEX1 is the most commonly mutated gene, accounting for ~70% of all ZSD cases. Peroxisomes are organelles essential for metabolising very-long-chain fatty acids, bile acids, and plasmalogens.
Practical takeaway
The G843D variant is more common than many expect — carrier frequency may be as high as 1 in 50-100 in some populations. Partner carrier testing is available. If both parents carry PEX1 variants, the specific combination determines severity — two mild variants tend to produce milder disease. 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 PEX1 is sufficient for normal peroxisome biogenesis. Your carrier status becomes relevant if your partner also carries a PEX1 variant (or a variant in another PEX gene — 13 PEX genes can cause ZSD). The severity in an affected child depends on which specific variant combination they inherit.
Population Context
PEX1 G843D is found across diverse populations, predominantly in Europeans. ZSD overall has an incidence of approximately 1 in 50,000 births. PEX1 variants account for ~70% of cases. The G843D variant's relatively high carrier frequency suggests many mild ZSD cases may go undiagnosed.
Limitations
23andMe tests 1 PEX1 variant. ZSD involves 13 PEX genes. A negative PEX1 result does not rule out ZSD carrier status via other genes. Comprehensive peroxisomal disorder panels cover all PEX genes.