Mutation in the AGK gene in two siblings with unusual Sengers syndrome

• Published in: Metabolic brain disease Vol. 32; no. 6; pp. 2149 - 2154
• Main Authors: Allali, Sanae, Dorboz, Imen, Samaan, Simon, Slama, Abdelhamid, Rambaud, Charlène, Boespflug-Tanguy, Odile, Sarret, Catherine
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2017; Springer Nature B.V; Springer Verlag
• Subjects: Acidosis; Acylglycerol kinase; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cardiomyopathies - genetics; Cardiomyopathy; Cataract - genetics; Child; Child, Preschool; Diagnosis; Hereditary diseases; Humans; Hypotonia; Intellectual Disability - genetics; Intolerance; Lactic acidosis; Life Sciences; Male; Metabolic Diseases; Metabolic disorders; Mutation; Myopathy; Neonates; Neurology; Neurons and Cognition; Neurosciences; Oncology; Phenotype; Phosphotransferases (Alcohol Group Acceptor) - genetics; Pregnancy; Prenatal diagnosis; Short Communication; Siblings; Sengers syndrome; Intellectual deficiency; Nervous system; Myocardiopathy; Congenital cataract; Exome sequencing
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-017-0101-6

Sengers syndrome is a rare autosomal recessive metabolic disorder caused by lack of acylglycerol kinase due to mutations in the AGK gene. It is characterized by congenital cataract, hypertrophic cardiomyopathy, myopathy and lactic acidosis. Two clinical forms have been described: a severe neonatal form, and a more benign form displaying exercise intolerance. We describe two siblings with congenital cataract, cardiomyopathy, hypotonia, intellectual disability and lactic acidosis. Whole exome sequencing revealed a homozygous c.1035dup mutation in the two siblings, supporting a diagnosis of Sengers syndrome. Our patients presented an intermediate form with intellectual deficiency, an unusual feature in Sengers syndrome. This permitted a prenatal diagnosis for a following pregnancy.