Tyrosinemia Type I (Hepatorenal Tyrosinemia)
Summary
Tyrosinemia type I is a metabolic condition where the body cannot complete the final step of tyrosine breakdown. Toxic metabolites (fumarylacetoacetate and succinylacetone) accumulate, causing severe liver damage, kidney dysfunction, and a painful neurological crisis resembling acute porphyria.
Practical takeaway
Particularly relevant if your partner is of French Canadian (especially Saguenay-Lac-Saint-Jean) or Finnish descent. Carrier testing is available. The reassurance: nitisinone treatment has transformed outcomes, and newborn screening catches the condition at birth. 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 FAH produces sufficient enzyme. Standard 25/50/25 recessive inheritance applies. This becomes relevant if your partner is also a carrier.
Population Context
The IVS12+5G>A variant produces a carrier frequency of ~1 in 20-25 in the Saguenay-Lac-Saint-Jean region of Quebec — one of the highest carrier rates for any metabolic condition worldwide. Carrier frequency is elevated in broader French Canadian and Finnish populations. The condition occurs in all ethnic groups at lower rates.
Limitations
23andMe tests 4 of over 100 known pathogenic FAH variants. Coverage is focused on founder variants. A "not detected" result provides incomplete reduction in carrier risk.
Sources (4)
- ClinVar: FAH pathogenic/likely pathogenic variant database↗
- OMIM: #276700 (Tyrosinemia, Type I)↗
- Chinsky et al. (2017), "Diagnosis and treatment of tyrosinemia type I" — Genetics in Medicine↗
- De Laet et al. (2013), "Recommendations for management of tyrosinemia type I" — Orphanet Journal of Rare Diseases↗