IEMbase 0019: FAH-related fumarylacetoacetase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 19 |
| Nosology | 1.4.07.01 |
| Gene | FAH |
| External IDs | OMIM:276700 |
| Generated mapping | MAPPED by alias_exact:fumarylacetoacetase deficiency |
| Candidate DisMech targets | Tyrosinemia_Type_I.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents hereditary tyrosinemia type I. The characteristic clinical feature is renal tubulopathy, with additional liver failure, hepatocellular carcinoma/hepatoblastoma, hypertension, nephrocalcinosis, renal enlargement, chronic renal failure, rickets, porphyria-like neurologic crises, neurocognitive and behavioral issues, corneal erosion, lacrimation, and photophobia.
The biochemical signature is highly concordant with HT1: elevated succinylacetone in dried blood spot, plasma, and urine; elevated tyrosine; elevated urinary delta-ALA; high alpha-fetoprotein; reduced RBC porphobilinogen synthase; and elevated tyrosine-pathway organic acids. Treatments include nitisinone, tyrosine/phenylalanine restriction, and liver transplantation.
DisMech phenotype coverage
The generated mapping to Tyrosinemia_Type_I.yaml is correct. DisMech covers
acute liver failure, hepatic fibrosis/cirrhosis, hepatocellular carcinoma, renal
tubular dysfunction, rickets, peripheral neuropathy, abdominal pain,
encephalopathy, respiratory failure, neurocognitive impairment, failure to
thrive, hepatomegaly, coagulopathy, elevated AFP, and edema. Biochemical
coverage includes succinylacetone, tyrosine, AFP, delta-ALA, and
fumarylacetoacetate. Treatments include nitisinone, dietary tyrosine and
phenylalanine restriction, liver transplantation, newborn screening, supportive
care, genetic counseling, and neurocognitive assessment/therapy.
Concordance and completeness
Judgement: correct mapping and high concordance for core HT1 liver, renal, and biochemical features.
IEMbase adds nephrocalcinosis, renal enlargement, hypertension, corneal erosion/lacrimation/photophobia, RBC porphobilinogen synthase, and explicit DBS/plasma/urine succinylacetone compartments. DisMech adds mechanistic detail for toxic fumarylacetoacetate/maleylacetoacetate, mitochondrial apoptosis, succinylacetone-heme interaction, residual HCC risk under NTBC, and clinical supportive care.
Curation actions
- Keep the generated mapping.
- Consider adding nephrocalcinosis, hypertension, and ocular symptoms if supported by HT1 evidence.
- Consider whether RBC porphobilinogen synthase belongs as a biochemical marker alongside delta-ALA.