Propionic Acidemia
What is propionic acidemia (PA)?
PA is a genetic disorder (autosomal recessive) in which a defective enzyme, propionyl-coenzyme A carboxylase, results in the accumulation of propionic acid. Individuals are unable to break down parts of protein and some types of fat. This results in a buildup of dangerous acids and toxins, which can damage a person’s organs. PA can result in brain damage, heart and liver conditions, seizures, and developmental delay.
What are the symptoms of PA?
Symptoms may include:
- Refusal to eat
- Poor sucking ability
- Vomiting
- Dehydration
- Lethargy
- Encephalopathy
- Acidosis
- Hyperammonemia
- Hypoglycemia
- Immunocompromised (patients who are poorly controlled)
- Mental impairment, coma, and death if a person does not receive treatment
- Pancreatitis and cardiomyopathy (some children with PA are more prone)
- Predisposed to bilateral infarcts of the basal ganglia involving the caudate, putamen, and globus pallidus (basal ganglia infarctions result in dystonia, choreoathetosis, and dementia)
Lab test results:
- Increased blood values—ammonia, glycine, Β-hydroxybutyrate, and acetoacetate
- Complete blood count (CBC)—may show neutropenia and thrombocytopenia
- Increased urine values—methyl citrate, 3-hydroxypropionate, propionyl glycine, tiglate, and tiglyl glycine
What is the survival rate for patients with PA?
Patients with early-onset PA are characterized by mental retardation and early death. The median survival of this group is 3 years of age.
How is PA diagnosed?
Most states provide comprehensive newborn screening for PA (via a heal stick within 24–48 hours following birth). Diagnosis of acute onset cases typically is made when newborns go into metabolic crisis in the first few days of life. Late onset cases, in states where comprehensive newborn screening is not available, usually are diagnosed in the emergency room following a traumatic metabolic crisis.
What is the treatment for PA?
Restriction of four amino acids (valine, isoleucine, methionine, and threonine) and odd-chained fats is the treatment. Under normal conditions, infants will require a minimum of 1.5 milliliters (mL) fluid/kilocalorie (kcal) and 1.0 mL fluid/kcal for children and adults. Fluid requirements are increased during fever or catabolic crisis.
It is necessary to avoid the following fats:
- Butter
- Cream
- Lard
- Olive oil
- Excess polyunsaturated fatty acids
- Breads containing added sodium or calcium propionate
The amount of intact protein consumed is adjusted based on plasma concentrations of specific amino acids, blood ammonia concentration, plasma transthyretin concentrations (measures protein status), and growth status.
The diet is supplemented with levocarnitine, usually at a dose of 100–300 milligrams (mg)/kilogram (kg)/day, because L-carnitine buffers the acyl-CoA metabolites that accumulate when a person follows a diet that is restricted in protein. Ingestion of excess oral L-carnitine might cause gastrointestinal symptoms and fish odor. Biotin supplementation at a dose of 10 mg/day also is required, because biotin is a cofactor for propionyl-CoA carboxylase. Some patients will not respond to biotin supplementation.
Most children with PA require gastrostomy tubes, because they often have no appetite and usually have food aversions. In-home testing for ketones, especially during suspected infections, is strongly recommended. Dialysis sometimes is required during life-threatening acute phases of illness. The use of parenteral nutrition during acute crises is shown to minimize catabolism and improve recovery in these patients.
Inadequate intake of the four amino acids will result in the following:
Valine
- Poor appetite
- Drowsiness
- Excessive irritability
- Weight loss or decrease in weight gain
- Decreased plasma albumin level
Isoleucine
- Weight loss or decrease in weight gain
- Redness of buccal mucosa
- Fissures at corners of mouth
- Tremors of extremities
- Decreased plasma cholesterol
- Skin desquamation
- Corneal de-epithelialization
- Increased concentration of plasma lysine, phenylalanine, serine, tyrosine, and valine
Methionine
- Decreased cholesterol
- Increased plasma phenylalanine, threonine, and tyrosine concentrations
Threonine
- Arrested weight gain
- Glossitis
- Redness of buccal mucosa
- Decreased plasma threonine and globulin concentrations
Initially, it is necessary to measure the plasma concentrations of these four amino acids daily by qualitative methods. Plasma glycine often is elevated in patients with PA. Improvement in plasma glycine concentration suggests better metabolic control.
References and recommended readings
Acosta PB, Yannicelli S. Protocol 13: propionic or methylmalonic acidemia. In: Ross Metabolic Formula System Nutrition Support Protocols. 4th ed. Columbus, OH: Ross Product Division, Abbott Laboratories; 2001:235-266.
Mandava P. Overview of propionic acidemia.
Available at: http://emedicine.medscape.com/article/1161910-overview. Accessed January 19, 2012.
Propionic Acidemia Foundation. Search for a cure: hope for our children.
Available at: http://pafoundation.com/. Accessed September 5, 2011.
Review Date 1/12
G-1772
