Expanding the clinical phenotype of the mitochondrial m.13513G>A mutation with the first report of a fatal neonatal presentation

• Published in: Developmental medicine and child neurology Vol. 53; no. 6; pp. 565 - 568
• Main Authors: VAN KARNEBEEK, CLARA D M, WATERS, PAULA J, SARGENT, MICHAEL A, MEZEY, MICHELLE M, WONG, LEE‐JUN, WANG, JING, STÖCKLER‐IPSIROGLU, SYLVIA
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2011; Mac Keith Press
• Subjects: Adult; Child; DNA, Mitochondrial - genetics; Family Health; Female; Humans; Infant, Newborn; Magnetic Resonance Imaging; Male; MELAS Syndrome - genetics; MELAS Syndrome - pathology; Mutation - genetics; Phenotype
• ISSN: 0012-1622; 1469-8749
• DOI: 10.1111/j.1469-8749.2010.03907.x

Diagnosis of mitochondrial disease is often a challenge because of the extreme heterogeneity of the clinical phenotype and the variety of underlying gene defects. Insight into the range of clinical phenotypes associated with a particular mitochondrial DNA mutation will facilitate better recognition of patients at risk by focused gene testing. We present a family affected by the mitochondrial m.13513G>A (p.D393N, ND5) mutation, illustrating a previously unreported degree of clinical heterogeneity, varying from mitochondrial encephalopathy with lactic acidosis and stroke‐like episodes (MELAS) in a 10‐year‐old female, to a fatal neonatal course with metabolic acidosis and hypotonia in a younger sister, to absence of medical problems in the mother. The mutation loads ranging from 66% in the deceased neonate to 30% in the female with MELAS and 7% in the asymptomatic mother, correlated with severity of the clinical phenotype. The importance of proactive collection and storage of appropriate samples during the diagnostic work‐up of an acutely ill or deceased neonate, allowing subsequent mitochondrial investigations, is hereby illustrated.