Description, Causes and Risk Factors:
Propionic acidemia is an autosomal recessive genetic disorder of amino acid metabolism. It is the most common of the organic acidurias. In the U.S., PA is estimated to strike once in every 100,000 births. A deficiency in propionyl-CoA carboxylase (PCC) causes PA patients to produce propionic acid, methyl citrate and other toxins when a diet high in protein is consumed. PCC is a biotin-dependent enzyme that functions in the degradation of methionine, valine, threonine, isoleucine, odd-chain fatty acids and cholesterol.
Propionic acidemia is caused by defects in either the PCCA (chromosome 13q32) or PCCB (chromosome 3q21-q22) genes.
Propionic acidemia is inherited in an autosomal recessive manner. It affects both boys and girls equally. Everyone has a pair of genes that make the PCC enzyme (Propionyl-CoA Carboxylase). In children with PA, neither of these genes works correctly. These children inherit one non-working gene for the condition from each parent.
Parents of children with PA rarely have the disorder themselves. Instead, each parent has a single non-working gene for PA. They are called carriers. Carriers do not have PA because the other gene of this pair is working correctly.
When both parents are carriers, there is a 25% chance in each pregnancy for the child to have PA. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.
Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening.
When propionic acidemiais suspected on the basis of electrolyte and arterial blood gas abnormalities, eliminate the common causes of ketoacidosis and lactic acidosis first. Seizures, diabetes, alcoholic ketoacidosis, liver disease, shock, and anoxic and/or ischemic injury of tissues are often present with acidosis.
If the clinical picture suggests a metabolic disorder, a presumptive diagnosis may be made on the basis of blood analysis for ammonia levels, amino acids, and organic acids. Serum levels of ammonia, glycine, B-hydroxybutyrate, and acetoacetate should be elevated. A complete blood count (CBC) may reveal neutropenia and thrombocytopenia.
Perform a urinalysis for amino acids and organic acids. Methyl citrate, 3-hydroxy propionate, propionyl glycine, tiglate, and tiglylglycine should be increased in the urine.
Make a definitive diagnosis after an enzyme analysis of fibroblasts is done. The results may show a severely depressed level of propionyl-CoA carboxylase. Genetic mutation analysis can also be undertaken. During the workup of a young patient with suspected stroke, exclude other causes of stroke by obtaining blood, brain, vascular, and cardiac studies.
Imaging studies: Acute changes in neurologic status (e.g., stroke, seizure, encephalopathy) warrant a neuroimaging study. Several reports confirm that patients with propionic acidemia and movement disorders most likely have lesions in the bilateral lenticular and caudate nuclei. By convention, computed tomography (CT) scanning and magnetic resonance imaging (MRI) were used in these reports to identify these lesions. However, positron emission tomography (PET) scanning has subsequently been used in patient evaluation, to show decreased glucose uptake in the basal ganglia.
At present, management of PA consists of strict dietary control, with the offending amino acids greatly restricted. The challenge to the clinician is to provide adequate calories and protein for growth and development of the patient without causing adverse symptoms that could progress to ketoacidosis or a metabolic decompensation. Avoiding a metabolic crisis is of primary concern to all who are involved in the care of a PA patient. Serum amino acid levels are frequently monitored and numerous dietary changes are usually necessary to find the optimal level of nutrients for each individual. One complicating factor in treating PA is that each individual produces a unique amount of PCC. Each person's diet is therefore unique, depending on the effect of individual mutations in PCCA or PCCB, the genes involved in producing PCC. The need for differing amounts of protein makes it impossible for clinicians to construct an "average" PA diet. Most PA patients develop a secondary carnitine deficiency and are therefore supplemented with L-carnitine, as well as biotin, a vitamin co-factor for PCC. Additionally, each PA patient reacts to dietary management differently depending upon the other aspects of his or her genetic makeup. Allergies, pancreatitis, diabetes insipidus, cardiomyopathy, hypoglycemia, decreased gut motility and hyperammonemia all complicate treating PA. Management of PA is a never-ending and time-consuming endeavor which must be maintained over a lifetime.
Dietary control, however, is an inadequate way to treat PA. Even the most well-managed individuals suffer ongoing damage to major organs such as liver, pancreas, brain, kidneys and heart. The damage may not be seen until years after diagnosis, but constant production of toxic metabolites, even at low levels will eventually take it's toll on the body. The advent of expanded newborn screening is now allowing for the identification of new PA cases that can be treated from birth. Fortunately these children will have a chance to flourish, but major illness can still cause a rapid slide to metabolic instability. The illusion of health can quickly fade when illness causes metabolic dysfunction and a cascade of difficult to manage conditions creates a complicated set of problems for physicians. PA individuals identified early via tandem mass-spec newborn screening may live longer, but they are no less immune to the ongoing life-threatening issues that face all those living with PA.
NOTE: The above information is for processing 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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