Paediatrics: Disorders of organic acid metabolism

Disorders of organic acid metabolism

A large group of disorders characterized by a broad range of clinical symptoms and signs varying in seriousness from trivial to lethal. Includes developmental delay, poor growth, and episodic illnesses with vomiting and metabolic acidosis. Some of these may be precipitated by prolonged fasting or minor viral infection. May be associated with hypoglycaemia and ketosis or ketoacidosis.

•   Characterized by urinary excretion of abnormal types and amounts of organic acids.

•   Diagnosis by urinary organic acid profile.

•   Treatment: avoid prolonged fasting, and administer extra carbohydrate during illness.

Examples include the following.

Methylmalonic acidaemia (MMA)

Caused by methylmalonyl-CoA mutase deficiency. Commonly presents in the newborn period with:

•   severe metabolic acidosis;

•   acute encephalopathy;

•   hyperammonaemia;

•   neutropenia and thrombocytopenia.

3-hydroxy-3-methyl-CoA (HMG-CoA) lyase deficiency

May present in the newborn period with severe metabolic acidosis, poor feeding and vomiting, lethargy, altered level of consciousness, hypoglycae-mia, and hyperammonaemia.

Glutaric aciduria

•   GluA type 1 is caused by deficiency of mitochondrial glutaryl-CoA dehydrogenase. The condition presents in infancy with episodes of hypotonia, dystonia, opisthotonus, grimacing, fisting, tongue thrusting, and seizures.

•   GluA type II is caused by deficiency of mitochondrial electron transport falvoprotein or dehydrogenase. It may present in the following ways.

•   Neonatal disease: with or without dysmorphism (abnormal facies, muscular defects of the abdominal wall, hypospadias in boys, cystic kidneys); hypotonia; hepatomegaly; hypoketotic hypoglycaemia; metabolic acidosis; hyperammonaemia.

Later-onset disease: episodic metabolic acidosis, failure to thrive, hypoglycaemia, hyperammonaemia, and encephalopathy.