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Título

CASE REPORT: A PATIENT WITH CEREBELLAR ATAXIA AND A ITPR1 GENE MUTATION

RESUMO

Case presentation: A previously healthy 40-year-old female presented a 4-year history of gait imbalance and dysarthria. In the past 2 years, she developed head and upper limb tremor. Her parents were both alive at the age of 66 (father) and 60 (mother), both reported by the patient as asymptomatic. She was of Portuguese ancestry on the maternal side and Italian and German ancestry on her paternal side. She had a 16-year-old daughter, also reported asymptomatic. On the neurological examination, she presented tandem gait ataxia, dysdiadochokinesia, dysmetria, nystagmus, hypermetric saccades, and mild lower limb spasticity. Her ocular movements, cognition, and peripheral system were unaffected. Unfortunately, her family members could not be examined, as they currently live in another city. Ancillary workup for acquired ataxias, including vitamin E, alpha-fetoprotein, serology testing, and B12 vitamin were all normal. Brain magnetic resonance imaging (MRI) showed only mild cerebellar atrophy. Cervical MRI and nerve conduction studies were unremarkable. The patient was tested for spinocerebellar ataxias (SCA) type 3 and type 10, both negative. Whole-exome sequencing revealed a heterozygous Arg275Trp variant in the PRKN gene and a heterozygous Asp1882Asn variant in the ITPR1 gene. With the identification of the ITPR1 mutation, the diagnosis of SCA 15 was established. Discussion: The ITPR1 gene is in the 3p26 chromosome, and encodes the inositol 1,4,5-triphosphate receptor type 1. Mutation of the gene is transmitted in an autosomal dominant manner, and this phenotype was correlated to several neurological syndromes, such as SCA 15, SCA 29, Under-Tan syndrome, and Gillespie syndrome. The mild symptomatology showed by the patient suggests the diagnosis of SCA 15. Final comments: Slowly progressive cases of cerebellar ataxia can often give the impression of a sporadic or acquired etiology due to an apparent lack of family history. After reasonable exclusion of such causes, the possibility of a genetic etiology should be raised and properly evaluated.

Palavras Chave

Movement disorders, Neurogenetics, Ataxia; Spinocerebellar ataxia