2025/12/09 by Jeremy Cajina-Clark, Joel Smith, Yoke Leong +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Porphyrin Metabolism and Disorders #Metabolism and Genetic Disorders #Neurological diseases and metabolism
paper · pdf · doi:10.1002/jmd2.70056
openalex publication_date 2025/12/09 · openalex created_date 2025/12/10 · openalex updated_date 2026/07/28
ABSTRACT Leukodystrophy due to biallelic HMBS variants is a rare condition distinct from acute intermittent porphyria (AIP). It is characterised by progressive leukoencephalopathy rather than acute attacks of neurovisceral symptoms. We report the ongoing clinical progression of a patient with leukodystrophy due to homozygous variants in HMBS [c.251C>A, p.Ala84Asp] despite liver transplantation. We demonstrate that porphyrin precursor levels are unchanged following liver transplantation in the periphery and that porphyrin precursor levels are constitutively elevated in the cerebrospinal fluid and are not reduced by haem arginate therapy. Liver transplantation and hepatically directed therapies are not likely to be effective for leukodystrophy due to biallelic HMBS variants. Alternative treatment strategies should be developed for effective management of this disorder. One‐liner: Leukodystrophy due to biallelic HMBS variants is unlikely to be cured by liver transplantation or other hepatically directed therapies.