Objective: The aim of this study is to describe a case report of a Brazilian patient with sporadic cerebellar ataxia, associated with hypogonadotropic hypogonadism, and PNPLA6 gene mutation.

Background: Hereditary ataxias represents a heterogeneous group of neurodegenerative diseases, including the autosomal recessive cerebellar ataxias (ARCAs) and autosomal dominant cerebellar ataxias, currently known as spinocerebellar ataxias (SCAs). The most common forms of ARCAs are Friedreich´s Ataxia and Ataxia Telangiectasia, and more rarely, a peculiar form of ARCAs is characterized by association with hypogonadotropic hypogonadism. PNPLA6 gene mutations are associated to Boucher-Neuhäuser syndrome (a combination of ARCAs and hypogonadotropic hypogonadism, associated to chorioretinal dystrophy) and also Gordon Holmes syndrome (ARCAs associated to hygonadotropic hypogonadism and pyramidal signs).

Methods: Case Report: A 24-year-old male was investigated due to a medical history of 1-year of a progressive disequilibrium, associated to episodic diplopia,. The clinical examination demonstrated a patient without secondary sexual characteristics, with an eunuchoid habitus. Neurological examination showed a mild gait ataxia (tandem gait), and horizontal gaze-evoked nystagmus.

Results: Ophthamological examination was normal, as well as the retinography and optical coherence tomography (OCT). Brain MRI showed a mild cerebellar atrophy. Endocrinological investigation showed plasma testosterone levels of 196 ng/dl (6.8 nmol/l), SHBG of 80.9 nmol/l, free testosterone of 1.98 ng/dl (1.01% of total testosterone), serum FSH of 2.7 mUI/ml and serum LH of 2.4 mUI/l, confirming the diagnosis of hypogonadotropic hypogonadism. Our patient presented in exon 34 of the PNPLA6 gene the c.4081C>T, p.Arg1381* (introducing a premature stop codon) and in exon 29 the c.3373G>A, p.Asp1125Asn PNPLA6 gene mutation. Each parent was hetrozygote for one of this mutations, proven that they are in trans in the patient.

Conclusions: We present a case report of a Brazilian patient with sporadic, progressive cerebellar ataxia, associated with hypogonadotropic hypogonadism, in whom the Gordon Holmes syndrome was confirmed by the demonstration of a compound heterozygote mutation in the PNPLA6 gene.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sporadic-cerebellar-ataxia-associated-with-hypogonadotropic-hypogonadism-and-pnpla6-gene-mutation-case-report-in-a-brazilian-patient/