Phenotypic spectrum of mutations in IBA57, a candidate gene for cavitating leukoencephalopathy

IBA57 is involved in the biogenesis of mitochondrial [4Fe-4S] proteins. Eighteen cases with IBA57 mutations have been reported to date. We described a novel phenotype in 11 children with cavitating leukoencephalopathy and summarized the phenotypic spectrum of IBA57 mutations. The median age of onset was 9 months, with an initial presentation of motor regression. Deterioration of neurological function reached its peak within 4 months. The median interval between onset and last follow-up was 2.9 years (0.4-10.0). All cases survived and remained stable. Severe motor handicap was observed in 50.0% of the patients, 52.9% to 71.4% had a delay in communication, problem solving or personal-social skills, and 20.0% had mild symptomatic fluctuations. In the peak phase, magnetic resonance imaging (MRI) lesions were mainly observed in the periventricular/central white matter, and cavitating lesions and patchy high diffusion-weighted imaging (DWI) signals were observed. The numbers and extent of restricted diffusional lesions were reduced, and atrophy was prominent in the recovery phase. Eight novel mutations in IBA57 were identified in our study. This study provided more information about the natural history and evolution of neuroimaging. Combined with previously reported patient studies, our findings suggest that defects in IBA57 can produce diverse phenotypes. IBA57 should be considered a candidate gene for cavitating leukoencephalopathy.