Depletion of mitochondrial DNA in the liver of a patient with lactic acidemia and hypoketotic hypoglycemia

• Published in: The Journal of pediatrics Vol. 128; no. 5; pp. 679 - 683
• Main Authors: Maaswinkel-Mooij, P.D., Van den Bogert, C., Scholte, H.R., Onkenhout, W., Brederoo, P., Poorthuis, B.J.H.M.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.05.1996; Elsevier
• Subjects: Acidosis, Lactic - complications; Biological and medical sciences; Carbohydrates (enzymatic deficiencies). Glycogenosis; DNA, Mitochondrial - isolation & purification; Electron Transport; Errors of metabolism; Fatal Outcome; Humans; Hypoglycemia - complications; Infant; Liver Failure - enzymology; Liver Failure - etiology; Liver Failure - metabolism; Liver Failure - pathology; Male; Medical sciences; Metabolic diseases; Mitochondria, Liver - enzymology; Mitochondria, Liver - genetics; Oxidoreductases - metabolism; Human; Hyperlactacidemia; Pathophysiology; Deficiency; Exploration; Hepatic disease; Infant; Mitochondrial DNA; Hypoglycemia; Case study; Metabolic disorder; Respiratory chain; Enzymatic activity; Digestive diseases; Complication; Lactic acid
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/S0022-3476(96)80134-X

An infant with feeding difficulties, hypotonia, lactic acidemia, and severe hypoketotic hypoglycemia died at the age of 7 months of liver disease. Electron microscopy revealed abnormal mitochondria. Biochemical studies of mitochondria) enzymes in liver showed a decreased activity of complexes I, III, and IV. Mitochondrial DNA (mtDNA) content was reduced in liver (7% of the mean value in control subjects) and in muscle (50%). In kidney, brain, and heart, the mtDNA content was normal. The liver-specific mtDNA depletion syndrome in this patient manifested itself with features of both a respiratory chain defect and a mitochondria) fatty acid oxidation defect. Syndromes involving depletion of mtDNA can be diagnosed only when both the activity of the respiratory chain enzymes and the content of mtDNA are investigated in the most affected tissues.