CA8-related cerebellar ataxia is a rare form of hereditary ataxia. It shares some phenotypic overlap with CAMRQ1 (VLDLR), CAMRQ2 (WDR81) and CAMRQ4 (ATP8A2) although these represent discrete conditions with different molecular underpinnings. There is no data available regarding prevalence, however the condition is ultra-rare, reported in less than 10 unrelated individuals as of 2023 (ClinGen, four published unrelated families).
CA8-related cerebellar ataxia causes cerebellar atrophy (typically superior) with consequent ataxia and dysarthria in all reported individuals to date. Intellectual disability, tremor and loss of bipedal gait (quadrupedal gait) is variably reported, with one individual having normal intellect at 9 years. Penetrance appears to be complete, however severity of ataxia and the neurodevelopmental phenotype is variable.
This is an autosomal recessive condition, caused by biallelic (homozygous or compound heterozygous) mutations in CA8, a gene that encodes carbonic anhydrase-related peptide 8 (CARP8). CARP8 is thought to play a role in early development of the cerebellum.
CA8