Limited benefit of liver transplantation in a boy with biallelic severe deficiency of hydroxymethylbilane synthase and review of prior reported cases
Year: 2026
Type: article
Study design: Case Report
Abstract: Introduction: A male infant presented at three months of age with generalized ataxia, hypotonia, aspiration of liquids and recurrent generalized seizures. He was treated with levetiracetam and phenobarbital. Methods: Extensive testing, including whole genome sequencing was done. Results: gene: p.R167Q [maternal] and p.T35M [paternal]. Plasma and urine exhibited high concentrations of 5-aminolevulinic acid, porphobilinogen, and uroporphyrin 1. Activity of hydroxymethylbilane synthase in red blood cells of the child was markedly reduced [18 nmol uroporphyrin/ g hemoglobin /h; reference range: 60-335]; it was ∼50% of normal in parents. The findings supported the diagnosis of biallelic severe HMBS deficiency with severe disease phenotype. A 5-day course of intravenous heme led to no observable clinical improvement. Orthotopic liver transplantation at the age of 15 months led to only mild transient improvement. Developmental delays and seizures persisted. MRI scans of the brain showed progressive white matter volume loss, cystic changes, and multifocal supratentorial signal abnormalities. He died at 88 months of age. Findings at autopsy of the brain showed patchy gliosis and leukodystrophy. We also review 11 previously reported cases. Conclusion: No effective disease-modifying therapy currently exists for biallelic HMBS deficiency. Substantial neurological injury is present by the time of diagnosis and seems irreversible.
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,400
Funder: National Institutes of Health
OpenAlex ID: W7166322080