Objective: Spinocerebellar ataxia autosomal recessive type 7 (SCAR7) is a rare disorder caused by biallelic pathogenic variants in TPP1. It usually manifests in childhood or adolescence with ataxia, pyramidal signs, dorsal column dysfunction, tremor, and nystagmus, but without seizures or severe cognitive impairment.[1]Neuroimaging often shows cerebellar and brainstem atrophy. It was first described by Breedveld et al. in 2004 in a Dutch family. To date, fewer than ten cases have been reported in the literature.[2] Our male patient presented with late-onset ataxia, with genetic analysis revealing a novel homozygous TPP1 mutation and similar clinical features observed in seven family members.

Background: We present a case of SCAR7 with late-onset cerebellar and sensory symptoms and a significant family history. Genetic testing confirmed the diagnosis. Its unique features may offer valuable insights given the few reported cases.

Method: A patient with progressive gait disorder underwent comprehensive evaluation, including neurological examination, radiological, and electrophysiological studies. Due to a history of consanguinity and familial early-onset gait disturbances, clinical exome sequencing was performed.

Results: A 67-year-old man with a 4-year history of progressive gait disorder exhibited bilateral lower limb spasticity, impaired proprioception, a positive Romberg sign, and marked truncal ataxia with a wide-based gait and inability to tandem walk, but no limb ataxia. Family history was notable for consanguinity and multiple relatives with early-onset gait disturbances. Brain MRI showed diffuse cerebellar atrophy; spinal imaging was normal. ENMG was normal, but MEP indicated a conduction abnormality above L4. Genetic analysis identified a novel homozygous TPP1 c.1348C>A (p.Pro450Thr) variant, classified as likely pathogenic, confirming the diagnosis of SCAR7.

Conclusion: SCAR7 is a rare hereditary ataxia caused by mutations in the TTP1 gene. In this case, a patient with atypical late-onset sensory and cerebellar ataxia was found to carry a novel homozygous TTP1 variant, supporting the SCAR7 diagnosis, especially given the family history of similar symptoms. Continued case reporting is essential to improve knowledge of the disorder’s pathophysiology, clinical features, and progression.

References: 1.Sun, Y., et al., Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants in TPP1, the gene involved in classic late-infantile neuronal ceroid lipofuscinosis 2 disease (CLN2 disease). Hum Mutat, 2013. 34(5): p. 706-13.
2.Breedveld, G.J., et al., A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15. J Med Genet, 2004. 41(11): p. 858-66.
3.Holla, V.V., et al., Spinocerebellar ataxia recessive type 7 due to novel compound heterozygous variants in TPP1: First report from India. Parkinsonism Relat Disord, 2022. 94: p. 117-119.
4.Liu, R.H., et al., Compound heterozygous mutations in tripeptidyl peptidase 1 cause rare autosomal recessive spinocerebellar ataxia type 7: A case report. World J Clin Cases, 2023. 11(27): p. 6618-6623.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spinocerebellar-ataxia-recessive-type-7-scar7-in-a-consanguineous-family-a-case-report/