A homozygous mutation in the NDUFS1 gene presents with a mild cavitating leukoencephalopathy

• DOI: 10.1007/s10048-014-0412-2
• Publication Date: 2014-06-20T03:26:48Z
• Authors: Alireza Kashani; Isabelle Thiffault; Marie-Emmanuelle ...; Christine Saint-M...; Kether Guerrero; Luan T. Tran; Eric Shoubridge; Marjo S. van der ...; Nancy Braverman; Geneviève Bernard
• Keywords: Male; 0301 basic medicine; Electron Transport Complex I; Mitochondrial Diseases; Homozygote; Mutation, Missense; Brain; NADH Dehydrogenase; 3. Good health; 03 medical and health sciences; SDG 3 - Good Health and Well-being; Leukoencephalopathies; Humans; Child

We report a case of mild cavitating leukoencephalopathy associated with a homozygous c.755A > G (p.Asp252Gly) NDUFS1 mutation in a 7-year old boy. Biochemical analysis confirmed an isolated reduction in complex I activity. Magnetic resonance imaging of the brain showed a diffuse cystic leukoencephalopathy with the involvement of the corpus callosum and sparing of the gray matter. The clinical course was marked by an acute presentation of neurological deficits at 24 months followed by recurrent episodes of mild neurological deterioration, subsequent remissions, and prolonged periods of stability. This is one of the mildest known clinical presentations of complex I deficiency secondary to mutations in NDUFS1, expanding the clinical spectrum and natural history of this disorder. Consideration of clinical variability needs to be taken into account in patient management and family counseling.