Objective: To describe a novel mutation p.Pro193Arg of the ABCD1-Gene in a patient presenting with clinical phenotype of Adrenomyeloneuropathy (AMN).

Background: Adrenoleukodystrophy comprises progressive neurologic and endocrinological dysfunction. Several clinical phenotypes including AMN have been described so that these rare conditions are referred to as ALD/AMN-Complex. This complex in general entails X-linked peroxisomal disorders with a rise of very long chain fatty acid (VLFCA) which accumulate in all body tissues. AMN in particular develops at ages around 20-40 years and features progressive spasticity, polyneuropathy, ataxia, cognitive deficits and psychiatric disorders. Here, we report a 45-year old male presenting with a 13 year history of progressive gait disturbance. Although primary adrenal insufficiency as well as elevated VLFCA counts were diagnosed consecutive to episodes of dizziness, diagnosis of ALD/AMN was not considered in a first instance. Throughout his adulthood, the patient required repeated admission to psychiatric hospitals due to severe depressive episodes and to recurrent substance abuse. When presented to us, he showed severe spastic paraparesis with slight spasticity in the upper limbs and moderate dysmetria. Montreal Cognitive Assessment indicated no severe cognitive impairment (25/30). Nevertheless, signs of frontal disinhibition were traceable and positive palmomental reflex could be elicited. Cerebral and medullar MRI revealed leukoencephalopathy with predominant affection of the pyramidal tract and cervical myelopathy. Electrophysiological examinations additionally displayed signs of polyneuropathy along with upper neuron affection.

Method: ABCD1-Gene located on the X-chromosome was sequenced using Next-Generation Sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA).

Results: Genetic studies revealed a novel missense mutation c.578C>G in Exon 1 resulting in a prolin to arginin substitution on position 193 within the protein level. To the best of our knowledge, this specific mutation has not yet been reported in literature or described in common gene databases (X-ALD, HGMD, CLINVAR).

Conclusion: According to the clinical presentation, the elevated VLFCA levels and with respect to MRI results, p.Pro193Arg in ABCD-1 Gene appears as yet undetected and probably pathogenic mutation causing ALD/AMN-phenotype.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-p-pro193arg-missense-mutation-in-abcd1-gene-associated-with-phenotype-of-ald-amn-a-case-report/