title: Abnormal Glycosylation Profile and High Alpha-Fetoprotein in a Patient with Twinkle Variants.
abstract: 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.
authors.affiliation: Reference Center for Inborn Errors of Metabolic Disease, Hôpital Robert-Debré, AP-HP, Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Bouchereau
authors.affiliation: Biochimie métabolique et cellulaire, AP-HP Hôpital Bichat-Claude Bernard, Paris, France.|Inserm U773, centre de recherche Bichat Beaujon CRB3, Université Paris-Diderot, Paris, France.
authors.forename: Sandrine Vuillaumier
authors.initials: SV
authors.lastname: Barrot
authors.affiliation: Biochimie métabolique et cellulaire, AP-HP Hôpital Bichat-Claude Bernard, Paris, France.|Inserm U773, centre de recherche Bichat Beaujon CRB3, Université Paris-Diderot, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Dupré
authors.affiliation: Inserm U773, centre de recherche Bichat Beaujon CRB3, Université Paris-Diderot, Paris, France.
authors.forename: Stuart E H
authors.initials: SE
authors.lastname: Moore
authors.affiliation: Institut de Myologie, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Cardas
authors.affiliation: Génétique Clinique, AP-HP Hôpital Robert Debré, Paris, France.
authors.forename: Yline
authors.initials: Y
authors.lastname: Capri
authors.affiliation: Biochimie, AP-HP Hôpital Bicêtre, Le Kremlin Bicêtre, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Gaignard
authors.affiliation: Biochimie, AP-HP Hôpital Bicêtre, Le Kremlin Bicêtre, France.
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Slama
authors.affiliation: Service des explorations fonctionnelles, Hôpital Robert Debré, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Delanoë
authors.affiliation: Reference Center for Inborn Errors of Metabolic Disease, Hôpital Robert-Debré, AP-HP, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Ogier de Baulny
authors.affiliation: Biochimie métabolique et cellulaire, AP-HP Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Seta
authors.affiliation: Reference Center for Inborn Errors of Metabolic Disease, Hôpital Robert-Debré, AP-HP, Paris, France.|Inserm U1141, Hôpital Robert Debré, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Schiff
authors.affiliation: Institut de Myologie, Hôpital Pitié-Salpêtrière, Paris, France. l.servais@institut-myologie.org.
authors.forename: Laurent
authors.initials: L
authors.lastname: Servais