Propionic Acidemia (PA)
PA is inherited in an autosomal recessive pattern. Normally a person has two functional genes. In people with PA, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with PA typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of propionic acidemia do not typically have symptoms.
There are two forms of PA, neonatal-onset and late-onset.
Neonatal-onset: The neonatal-onset form of this disorder is severe and symptoms typically begin in the first few days of life. Symptoms begin as vomiting and poor feeding, but progress to seizures, coma and eventually death.
Late-onset: The symptoms of late-onset PA may be brought on by illness, injury or other physical stress including vomiting, protein intolerance and seizures. Long-term symptoms include a loss of developmental milestones, low muscle tone, susceptibility to infections, cardiomyopathy (heart muscle disease) and pancreatitis. Other symptoms may include growth impairment and intellectual disability. Damage may also occur to a specific part of the brain (basal ganglia).
- Incidence: The incidence of PA is estimated to be 1 in 50,000 to 1 in 100,000. PA is more common in the Inuit population and Saudi Arabians.
- New York State Method of Screening (First Tier): Screening for propionic acidemia is accomplished by measuring the acylcarnitine C3 by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None. Testing can be affected by: Newborn screening cannot distinguish between PA and methylmalonic acidemia or severe maternal vitamin B12 deficiency.
- Interpretation/reporting of data: Results are reported as within acceptable limits, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for propionic acidemia are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of propionic acidemia.
Diagnostic testing may include urine organic acid analysis, plasma amino acid analysis, PCCA and PCCB gene sequencing and PCC enzyme activity analysis.
Treatment is typically dietary management, including careful monitoring of protein intake. Medications may include carnitine, metronidazole and N-carbamoylglutamate. There have been reports of liver transplant as a treatment of PA. Additional medical care including admission to the hospital for intravenous feedings may be required during times of illness. In some cases, hemodialysis may be needed.
Outcome of the neonatal-onset form is poor. Outcome of the late-onset form is variable and dependent on multiple factors, including the severity of disease and response to treatments.
Propionic acidemia (PA) is an organic acid disorder (inherited metabolic disorder) because abnormal levels of organic acids build up in the bodies of those affected.
PA is caused by mutations in one of two genes, PCCA or PCCB. Several components of protein (amino acids) are converted to propionyl-CoA as part of normal metabolism. Mutations in the PCCA or PCCB gene cause a deficiency of propionyl-CoA carboxylase (PCCA, PCCB and biotin), which breaks down propionyl-CoA. If this does not happen, toxic metabolites accumulate and cause vomiting and neurological symptoms.