Organic acidemia

Organic acidemia

Description, Causes and Risk Factors:

The term "organic acidemia" applies to a group of disorders characterized by the excretion of non-amino organic acids in urine. Most organic acidemias result from dysfunction of a specific step in amino acid catabolism, usually the result of deficient enzyme activity. The majority of the classic organic acid disorders are caused by abnormal amino acid catabolism of branched-chain amino acids or lysine. The pathophysiology results from accumulation of precursors and deficiency of products of the affected pathway.

The accumulated precursors are themselves toxic or are metabolized to produce toxic compounds. The pathophysiology of these disorders is the result of toxicity of small molecules to brain, liver, kidney, pancreas, retina, and other organs. Some of these molecules, such as the glutaric acid metabolites, are thought to be excitotoxic to neurons and may affect N-methyl-D-asparate (NMDA) receptors.

Organic acidemias are divided into two categories: disorders of amino acid metabolism and disorders involving fatty acid oxidation. There are several dozen different organic acidemia disorders. They are caused by inherited deficiencies in specific enzymes involved in the breakdown of branched-chain amino acids, lysine, and tryptophan, or fatty acids. Some have more than one cause.

Amino acids are chemical compounds from which proteins are made. There are about 40 amino acids in the human body. Proteins in the body are formed through various combinations of roughly half of these amino acids. The other 20 play different roles in metabolism. Organic acidemias involving amino acid metabolism disorders include isovaleric acidemia, 3-methylcrotonyl-glycemia, combined carboxylase deficiency, hydroxy-methylglutaric acidemia, propionic acidemia, methylmalonic acidemia, beta-ketothiolase deficiency, and glutaric acidemia type I.

Fatty acids, part of a larger group of organic acids, are caused by the breakdown of fats and oils in the body. Organic acidemias caused by fatty acid oxidation disorders include, glutaric acidemia type II, short-chain acylcoenzyme A dehydrogenase (SCAD) deficiency, medium-chain acylcoenzyme A dehydrogenase (MCAD) deficiency, long-chain acylcoenzyme A dehydrogenase (LCAD) deficiency, very long-chain acylcoenzyme A dehydrogenase (VLCAD) deficiency, and long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency.

Respiratory chain deficiencies measured in tissues of persons with propionic and methylmalonic acidemia suggest that secondary mitochondrial damage plays a role in the organ damage seen in some affected individuals.

The organic acidemias considered in this overview are inherited in an autosomal recessive manner. At conception, each sib of a proband has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members is possible if the disease-causing mutations in the family are known.

There are more than 100 inborn errors of metabolism, many of which are organic acidemias, present in the neonatal period, with an approximate incidence of 1:1000 neonates.


Every child with an organic acidemia is different. Most babies with organic acidemias will look normal at birth. Symptoms of organic acidemias can appear shortly after birth, or they may show up later in infancy or childhood. Common symptoms of organic acidemias include weakness, vomiting, low blood sugar, hypotonia (weak muscles), spasticity (muscle stiffness) or other neurological symptoms.

Non-specific symptoms such as vomiting, refusal of feeds, failure to thrive, lethargy, breath-lessness, seizures and disturbed consciousness cannot distinguish organic acidemias from a wide variety of medical and surgical emergencies. Disorders associated with neutropenia and thrombocytopenia like propionic and methylmalonic acidemia are prone to be mistaken for neonatal sepsis.


Clinical laboratory findings that suggest an organic acidemia include acidosis, ketosis, hyperammonemia, abnormal liver function tests, hypoglycemia, and neutropenia. First-line diagnosis in the organic acidemias is urine organic acid analysis using gas chromatography with mass spectrometry (GC/MS), utilizing a capillary column. The urinary organic acid profile is nearly always abnormal in the face of acute illness with decompensation; however, in some disorders diagnostic analytes may be present only in small or barely detectable amounts when the affected individual is not acutely ill. Depending on the specific disorder, plasma amino acid analysis using a quantitative method such as column chromatography, high-performance liquid chromatography (HPLC), or GC/MS can also be helpful. A plasma or serum acylcarnitine profile can also provide a rapid clue to the diagnosis. Urine acylcarnitine profiling is more complex and interpretation can be difficult. Confirmatory testing involves assay of the activity of the deficient enzyme in lymphocytes or cultured fibroblasts and/or molecular genetic testing.

Prenatal diagnosis for pregnancies at increased risk varies by disorder and may include measurement of analytes in amniotic fluid, measurement of enzyme activity, or molecular genetic testing in cells obtained by CVS or amniocentesis.


Treatment of organic acidemia should be based on the following principles: 1) preventing accumulation of toxic substances (organic acids) by restricting proteins and other substrata in the diet, and by inhibiting catabolism avoiding prolonged fasting periods and treating infections promptly;2) eliminating toxic metabolites by exsanguinating transfusion, hemodialysis, or peritoneal dialysis and by administering L-carnitine; and 3) applying general support measures, such as correction of serum pH levels, assisted mechanical ventilation, and adequate hydration.

NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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