Liver Transplantation and Other Hepatically Directed Therapies Do Not Change the Biochemical Phenotype nor Halt Progression of Leukodystrophy due to Biallelic HMBS Variants: A Case Report

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.