Background:The mitochondrial calcium uptake protein 1(MICU1) is a newly discovered gene (2010).It is a subunit of the mitochondrial uniporter, a multisubunit calcium channel of the mitochondrial inner membrane. It regulates channel opening in response to intracellular calcium content and calcium transients. It`s mutation result in an early childhood onset of proximal muscle weakness, progressive extrapyramidal signs, and learning disabilities.Only 30 cases have been described in the literature. Objective: To describe the clinical characteristics, neuroloradiolgical , laboratory profiles of four cases diagnosed with MICU1 mutation from two Saudi consanguineous families .
Method: A retrospective chart review study of four cases diagnosed with MICU1mutation at a tertiary university center in Saudi Arabia.
Results: The phenotype associated with MICU1gene mutations in our patients is fairly consistent, although our case series is unique in that all the affected patients are a product of consanguineous marriages ,severity of the disease varies within the same family, extrapyramidal signs were not the major symptom initially, congenital heart disease and Arnold – Chiari malformation were additional clinical features . Early encephalopathic changes (slow background) with epileptiform discharges on EEG were seen in two patients, and evidence of mitochondrial disorder was detected on liver and muscle biopsy of one patient. A novel nonsense homozygous mutation c.547C>T (p. Gln 183*) was detected in one family, while a previously reported c.553C >T (p. Gln185*) was detected in the other family.
In conclusion, our findings expand the phenotypic and genotypic manifestations of MICU1 gene mutations.
Key Words: Mitochondrial calcium uptake protein 1, MICU1, Muscle weakness, Extrapyramidal signs, learning disabilities, MRI .