New cases of δ-aminolevulinic acid dehydratase deficiency: Functional insights into gene variants using an innovative mouse liver model.

ABSTRACT:

Background

Dysfunction of δ-aminolevulinic acid dehydratase (ALAD), the second enzyme involved in heme biosynthesis, leads to two pathologies: genetic and acquired. The genetic form is an ultrarare, severe childhood-onset disease inherited in an autosomal recessive manner, whereas the acquired form usually affects adults due to enzyme inhibition by specific chemicals.

Aims and patient cohort

This study reports the molecular characterization of three pediatric patients with genetic ALAD deficiency porphyria (ADP), including two siblings, and five adults who exhibited features suggestive of heavy metal poisoning. Furthermore, using an innovative mouse liver model, we performed in vivo functional analysis of the pathogenic variants and lead susceptibility alleles identified in

SUBMITTER: Di Pierro E 

PROVIDER: S-EPMC12678219 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature