Targeted gene approach with biochemical assay confirms ABCD1 mutation of X-linked adrenoleukodystrophy in a 62-year-old man with gait imbalance

• Published in: Neuromuscular disorders : NMD Vol. 29; no. 2; pp. 146 - 149
• Main Authors: Mauermann, Michelle L., Niu, Zhiyv, Renaud, Deborah L., Kemppainen, Jennifer L., Schultz, Matthew J., Klein, Christopher J.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01-02-2019
• Subjects: ABCD1; Adrenoleukodystrophy; Adrenoleukodystrophy - genetics; Adrenomyeloneuropathy; ATP Binding Cassette Transporter, Subfamily D, Member 1 - genetics; DNA Mutational Analysis; Gait Disorders, Neurologic - genetics; Humans; Male; Middle Aged; Mutation; Myelopathy; Peripheral neuropathy; Peroxisomal disorders; Adrenomyeloneuropathy; Myelopathy; Adrenoleukodystrophy; Peripheral neuropathy; ABCD1; Peroxisomal disorders
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2018.11.007

•Adrenomyeloneuropathy may present with only mild myelopathic features.•Targeted gene approach aids diagnosis in atypical presentations.•Functional assay confirmation is needed to confirm causality of genetic variants.
X-linked adrenoleukodystrophy is a peroxisomal disorder caused by a mutation in ABCD1 gene. The three main phenotypes of X-linked adrenoleukodystrophy include cerebral adrenoleukodystrophy, adrenomyeloneuropathy, and isolated primary adrenal insufficiency. More than 750 non-recurrent mutations exist throughout the coding region of the ABCD1 gene. We report a 62-year-old man with a 17-year history of progressive gait imbalance and numb feet. He had noted difficulty rising from a chair for 3 years. Examination revealed proximal lower limb weakness and length-dependent sensory loss with preservation of reflexes and unilateral Babinski sign. Electrodiagnostic evaluation confirmed a length-dependent sensorimotor peripheral neuropathy and proximal myopathy. Family history was remarkable for similar symptoms in 6 siblings. A targeted gene approach for 102 known peripheral neuropathy genes led to discovery of ABCD1 mutation confirmed by kindred evaluation and biochemical assay. This case highlights the importance of combining targeted gene approaches with functional assay confirmation especially for atypical clinical presentations.