Abstract

Objective: To report a 7 years old girl with genetic and biochemical characteristics of zellweger spectrum disorder who presented with phenotype and neuro imaging findings of adrenoleukodystrophy.

Methods: Target gene sequencing was performed by using a custom designed panel for this patient with focused mutation analysis on 16 peroxisomal genes included in the panel. Sanger sequencing was used to confirm the identified mutation.

Results: This patient was homozygote for a missense mutation in exon 2 of the PEX 12 gene; c.541T>G (p.Tyr181Asp) which is a conserved residue in the N-terminal region crucial for localization to peroxisomes. Her parents and healthy sister were also found to have the same heterozygote mutation.

Conclusion: We suggest that PEX 12 gene mutations with a milder phenotype may be a potential candidate for posterior dominant leukodystrophy of childhood resembling X-linked ALD. This is entitled to pseudo- ALD and may be a diagnostic possibility in patients who develop ALD phenotype and neuroimaging particularly, in girls.

Keywords: Zellweger spectrum disorder; Childhood onset; Pseudo-ALD; PEX 12 gene; Novel mutation

Abbreviations: PBD: Peroxisomal Biogenesis Disorders; ZS: Zellweger Syndrome; NALD: Neonatal Adrenoleukodystrophy; IRD: Infantile Refsum Disease