title: A patient with congenital hyperlactataemia and Leigh syndrome: an uncommon mitochondrial variant.
abstract: We report an uncommon mitochondrial variant in a baby girl with congenital hyperlactataemia and Leigh syndrome. The patient presented with a single episode of generalised clonic convulsion at day 19, and was found to have isolated and persistent hyperlactataemia ranging from 3.34 to 9.26 mmol/L. She had elevated serum lactate-to-pyruvate ratios of up to 35 and high plasma alanine concentration, indicative of a respiratory chain defect. At the age of 8 months, she developed evolving neurological and imaging features compatible with Leigh syndrome. Genetic testing for common mitochondrial DNA mutations, large mitochondrial DNA deletions, and selected nuclear genes was negative. Further analysis of lymphocyte mitochondrial DNA by sequencing revealed an uncommon heteroplasmic variant, NC_012920.1(MT-ND5):m.13094T>C (p.Val253Ala), which was previously shown to reduce complex I activity. In patients in whom there was a high suspicion of mitochondrial disorder, entire mitochondrial DNA analysis may be warranted if initial screening of common mitochondrial DNA mutations is negative.
authors.affiliation: Kowloon West Cluster Laboratory Genetic Service, Department of Pathology, Princess Margaret Hospital, Laichikok, Hong Kong.
authors.forename: C K
authors.initials: CK
authors.lastname: Ching
authors.forename: Chloe M
authors.initials: CM
authors.lastname: Mak
authors.forename: K M
authors.initials: KM
authors.lastname: Au
authors.forename: K Y
authors.initials: KY
authors.lastname: Chan
authors.forename: Y P
authors.initials: YP
authors.lastname: Yuen
authors.forename: Eric K C
authors.initials: EK
authors.lastname: Yau
authors.forename: Louis C K
authors.initials: LC
authors.lastname: Ma
authors.forename: H L
authors.initials: HL
authors.lastname: Chow
authors.forename: Albert Y W
authors.initials: AY
authors.lastname: Chan
mesh_terms: D000140:Acidosis, Lactic / Q000151:congenital* / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D019344:Lactic Acid / Q000097:blood; D007888:Leigh Disease / Q000235:genetics*; D019289:Pyruvic Acid / Q000097:blood; D012640:Seizures / Q000209:etiology; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial; D019344:Lactic Acid; D019289:Pyruvic Acid
keywords: Acidosis, lactic; Hong Kong; Leigh disease; Mitochondria; Mutation