Objective: We describe a 73-year old patient carrying a heterozygous mutation in aprataxin (APTX) gene presenting multiple system atrophy-parkinsonian variant (MSA-P).

Background: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive disorder due to mutations within the APTX gene associated with prominent cerebellar involvement. Previous association studies suggested MSA-cerebellar variant as possible phenotype associated with monoallelic APTX gene mutations.

Method: Whole exome sequencing was performed in order to (i) evaluate APTX mutation status and (ii) exclude gene variants previously associated with parkinsonism.

Results: We describe the case of a patient, presenting with parkinsonism with bilateral upper limb tremor at age 71, followed in the next two years by progressive urinary incontinence, orthostatic hypotension, recurrent falls, dysarthria and dysphagia to liquids. Past medical history was unremarkable except for hypercholesterolemia and mild arterial hypertension. Brain MRI exhibited mild cerebellar and putaminal atrophy. [123I]FP-CIT SPECT showed asymmetric (right-dominant) presynaptic striatal dopaminergic degeneration and a diagnosis of MSA-P was performed. An electroneurography showed diffused sensori-motor neuropathy predominant at lower limbs. There was only poor response to L-Dopa treatment. In the next two years the patient developed progressive respiratory failure with worsening of dysphagia and died at age 75.

Neuropsychological evaluation was normal except for mild verbal memory impairment and dyscalculia. Genetic analyses revealed a nonsense monoallelic mutation of APTX (c.837G>A; p.Trp279Ter), which causes AOA1 in homozygous state.

Conclusion: APTX monoallelic mutations could be associated to MSA-P phenotypes. Further studies including functional mutation analyses are warranted to confirm our hypothesis and elucidate the related pathogenic mechanisms.

References: Baba Y, Uitti RJ, Boylan KB, et al. Aprataxin (APTX) gene mutations resembling multiple system atrophy. Parkinsonism Relat Disord. 2007;13(3):139–42.

Salvatore E, Varrone A, Criscuolo C, et al. Nigrostriatal involvement in ataxia with oculomotor apraxia type 1. J Neurol. 2008;255(1):45–8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/heterozygous-aprataxin-gene-mutation-associated-with-atypical-multiple-system-atrophy-phenotype-a-case-report/