JIMD Reports, Volume 29

Bouchereau, Juliette, Barrot, Sandrine Vuillaumier, Dupré, Thierry, Moore, Stuart E H, Cardas, Ruxandra, Capri, Yline, Gaignard, Pauline, Slama, Abdelhamid, Delanoë, Catherine, de Baulny, Hélène Ogier, Seta, Nathalie, Schiff, Manuel, Servais, Laurent, Juliette Bouchereau, Sandrine Vuillaumier Barrot, Thierry Dupré, Stuart E. H. Moore, Ruxandra Cardas, Yline Capri, Pauline Gaignard, Abdelhamid Slama, Catherine Delanoë, Hélène Ogier de Baulny, Nathalie Seta, Manuel Schiff, Laurent Servais, Moore, Stuart E. H., Ogier de Baulny, Hélène

The C10orf2 gene encodes Twinkle, a protein involved in mitochondrial DNA (mtDNA) replication. Twinkle mutations cause mtDNA deletion or depletion and are associated with a large spectrum of clinical symptoms including dominant progressive external ophthalmoplegia (adPEO), infantile-onset spinocerebellar ataxia (IOSCA), and early-onset encephalopathy. The diagnosis remains difficult because of the wide range of symptoms and lack of association with specific metabolic changes. We report herein a child with early-onset encephalopathy, unusual abnormal movements, deafness, and axonal neuropathy. All laboratory investigations were normal with the exceptions of high alpha-fetoprotein levels and an abnormal glycosylation profile. These abnormal parameters resulted in misdiagnosis as a previously unidentified congenital disorder of glycosylation (CDG) type I syndrome. Whole exome sequencing revealed two point mutations in C10orf2 that were confirmed by Sanger sequencing; neither had been previously reported. This report enlarges the clinical phenotype of Twinkle mutations and suggests that an abnormal glycosylation profile suggestive of CDG type I associated with high blood alpha-fetoprotein levels without obvious cause should prompt Twinkle sequencing.