Home > D. Systemic pathology > Genetic and developmental anomalies > Genetic metabolic diseases > organic acidemias

organic acidemias

Thursday 24 March 2005

Definition: Organic acidemia, also called organic aciduria, is a term used to classify a group of metabolic disorders which disrupt normal amino acid metabolism, particularly branched-chain amino acids, causing a buildup of acids which are usually not present. The branched-chain amino acids include isoleucine, leucine and valine. The three main types of organic acidemia are: methylmalonic acidemia, propionic acidemia, isovaleric acidemia.

NB: Organic acids refer to the amino acids and certain odd-chained fatty acids which are affected by these disorders.

Types

- propionic acidemia
- methylmalonic acidemia
- methylmalonic aciduria and homocystinuria (cobalamine C and D disease)
- multiple carboxylase deficiency (holocarboxylase synthetase deficiency)
- multiple carboxylase deficiency (biotinidase deficiency)
- isovaleric acidemia
- glutaric aciduria type 1
- 3-methylcrotonyl CoA carboxylase deficiency (3-methylcrotonyl glycinuria)
- 3-methylglutaconic aciduria
- 3-hydoxyisobutyric aciduria
- malonic aciduria
- D-2-hydroxyglutaric aciduria
- L-2-hydroxyglutaric aciduria
- 2-oxoadipic aciduria
- 4-hydroxubutyric aciduria
- mitochondrial acetoacetyl-CoA-thiolase deficiency (3-oxothiolase deficiency)

- maple syrup urine disease (aminoacid metabolism)

Clinical synopsis

- neurological damage
- developmental delay
- poor feeding
- slow growth
- lethargy
- vomiting
- dehydration
- malnutrition
- hypoglycemia
- hypotonia
- metabolic acidosis
- ketoacidosis
- hyperammonemia
- death

Organic acidemias are usually always diagnosed in infancy. These disorders vary in their prognosis, from manageable to fatal, and usually affect more than one organ system, especially the central nervous system.

Diagnosis

Organic acidemias are characterized by urinary excretion of abnormal amounts or types of organic acids.

The diagnosis is usually made by detecting an abnormal pattern of organic acids in a urine sample by gas chromatography and mass spectrometry.

In some conditions, the urine is always abnormal, in others the characteristic substances are only present intermittently.

Many of the organic acidemias are detectable by newborn screening with tandem mass spectrometry.

Etiology

Most of the organic acidemias result from defective autosomal genes for various enzymes important to amino acid metabolism. Most are inherited as autosomal recessive diseases.

Neurological and physiological harm is caused by this impaired ability to synthesize a key enzyme required to break down a specific amino acid, or group of amino acids, resulting in acidemia and toxicity to specific organs systems.

Treatment and management

Treatment or management of organic acidemias vary. There are no effective treatments for all of the conditions, though treatment for some may include a limited protein/high carbohydrate diet, intravenous fluids, amino acid substitution, vitamin supplementation, carnitine, induced anabolism, and in some cases, tube-feeding.