Work

DNAJC12 Disease

Year: 2025

Type: article

Abstract: Background and Objectives: Autosomal recessive DNAJC12 disease, the most recently identified disorder of biogenic amine synthesis, presents with a broad clinical spectrum and variable outcomes, ranging from asymptomatic patients to early-onset parkinsonism. This study aimed to better outline the clinical phenotype and outcomes of DNAJC12 disease, the prognostic value of the metabolic and genetic biomarkers, and the treatment response. Methods: We systematically collected clinical, biochemical, and genetic data from 56 patients with DNAJC12 disease in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines: 51 from the literature since the disease was first described and 5 unpublished personal cases. Results: pathogenic variants, primarily for phenotypes A and C.Movement disorders responded positively to the various therapies in all symptomatic patients. The preventive effects on NDD and psychiatric problems were less clear. Discussion: DNAJC12 disease is a new metabolic neurodevelopmental disorder linked to parkinsonism. The combined effects of neurotransmitter depletion and disrupted enzyme proteostasis in dopaminergic and serotoninergic neurons may underlie the early neurodevelopmental presentation and subsequent neurologic and psychiatric disorders.

Source: Neurology Genetics

DOI: 10.1212/nxg.0000000000200335