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Introduction
Propionic acidemia is a metabolic disorder in which a defective form of the enzyme propionyl-coenzyme A (CoA) carboxylase results in the accumulation of propionic acid. More specifically, the metabolism of isoleucine, valine, threonine, and methionine produces propionyl-CoA. To a lesser degree, cholesterol and odd-chain fatty acids also contribute to propionyl-CoA levels. The enzyme propionyl-CoA carboxylase, which requires biotin as a cofactor, catalyzes conversion of propionyl-CoA to methylmalonyl-CoA. Propionic acidemia is an inherited autosomal recessive disease.

Symptoms
Patients suffering from Propionic acidemia may present with vomiting, dehydration, lethargy, and encephalopathy. Clinical and imaging evidence suggests that propionic acidemia predisposes patients to bilateral infarcts of the basal ganglia. Milder forms of this metabolic disorder may be characterized by the absence of some of the clinical conditions. Although most children have neurological damage during a metabolic crisis, rare cases without an identifiable factor have been reported. The metabolic crisis may result from changes in feeding, or they may be secondary to an infection.

Diagnosis
Patients whose disease is diagnosed before birth (from the family history or sibling history) or soon after birth have the best prognosis. Surtees et al divided patients with propionic acidemia into 2 subgroups: those with early onset disease presenting in the first week of life and those with late-onset disease presenting after age 6 weeks. The early onset group was characterized by mental retardation and early death, with the median survival period being 3 years. The late-onset group was characterized by severe movement disorders and dystonias. Patients with late-onset disease usually have permanent neurological damage. The differential diagnosis of propionic acidemia includes the following * Brainstem syndromes * Cyanotic heart disease * Marfan syndrome * Organic acidurias * Sickle cell disease * Thrombocytopenia * Basilar artery thrombosis * Disorders of carbohydrate metabolism * Fabry Disease * Mitochondrial myopathy, encephalopathy, lactic acidosis, and MELAS syndrome * Posterior cerebral artery stroke

Treatment
A protein-restricted diet is the cornerstone of treatment. A low-protein diet (1.5-2mg/kg/day), L-carnitine supplementation (100mg/kg/day), and biotin supplementation (10mg/day) are required. Carnitine, an enzyme involved in the metabolism of long-chain fatty acids, buffers the acyl-CoA metabolites that accumulate with protein-restricted diets. The acyl-carnitine that is produced by the buffering action is excreted in the urine. Biotin is a cofactor for propionyl-CoA carboxylase (and for 3 other carboxylases). Therefore, propionic acidemia may be present in a patient suffering from the broader metabolic problem of multiple carboxylase deficiency. Biotin responsiveness may depend on the genetic disposition of the patient as well as the time of diagnosis and the acuteness of the disease. In patients with biotin-unresponsive disease, restricting their intake of isoleucine, valine, threonine, and methionine is the only solution. Prompt dietary modification and supplementation may reverse clinical symptoms. The success of therapy can be measured as changes in propionic acid level in the serum. In the acute phase, identify and treat intercurrent infections that have triggered an acidotic episode. Any dietary modifications must be made in a clinical situation and consulting an appropriate physician is highly advised. Because gastrointestinal bacteria produce propionic acid, neomycin and metronidazole have been proposed as treatments. Clinical data about this treatment regimen are limited. Dialysis may be required for life-threatening acute phases of illnesses that are triggered by infections or other stresses.

http://emedicine.medscape.com/article/1161910-overview