Acidemia (Propionic)

Definition

Definition of Acidemia (Propionic)
Propionic acidemia, also known as propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia, is an autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia.

Propionic Acidemia is a rare disorder that is inherited from both parents. Being autosomal recessive, neither parent shows symptoms, but both carry a defective gene responsible for this disease. It takes two faulty genes to cause PA, so there is a 1 in 4 chance for these parents to have a child with PA.

Symptoms

Symptoms of Acidemia (Propionic)
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.

Causes

Causes of Acidemia (Propionic)
In order for the body to use protein from the food we eat, it is broken down into smaller parts called amino acids. Special enzymes then make changes to the amino acids so the body can use them.

Propionic acidemia occurs when an enzyme called “propionyl CoA carboxylase” (PCC) is either missing or not working properly. This enzyme’s job is to change certain amino acids so the body can use them. When this enzyme is not working, substances called glycine and propionic acid, along with other harmful substances, build up in the blood and cause problems.

Clinical

Clinical of Acidemia (Propionic)
Patients with Propionic Acidemia typically present in the first days of life with dehydration, lethargy, hypotonia, vomiting, ketoacidosis, and hyperammonemia. Seizures, neutropenia, thrombocytopenia, and hepatomegaly may be present. Untreated patients can progress to coma and die. Most patients who survive the neonatal period have episodes of metabolic acidosis precipitated by infection, fasting, or a high protein diet. In some cases, episodic hyperammonemia seems to predominate over the metabolic acidosis. Psychomotor retardation is a life-long complication. Some patients have first presented later in infancy with encephalopathy and associated ketoacidosis, or developmental delay.

Testing

Testing of Acidemia (Propionic)
Newborns can be screened for Propionic Acidemia using tandem mass spectrometry analysis of a heel-stick dried blood spot. The finding of elevated three-carbon acylcarnitine (C3) indicates a possible metabolic defect, either PA, Methylmalonic Acidemia, or less likely a defect in biotin metabolism. With Methylmalonic Acidemia, C4-dicarboxylic acylcarnitine may also be found, helping distinguish this disorder from Propionic Acidemia. To make a diagnosis, further testing is required. Urine organic acid analysis of a patient with Propionic Acidemia will demonstrate massive elevations of propionic acid and related compounds such as methylcitrate, propionylglycine, ß-hydroxypropionate, and tiglic acid. In Propionic Acidemia, carnitine deficiency due to increased renal excretion of propionyl carnitine is often seen.

Treatment

Treatment of Acidemia (Propionic)
Treatment of Propionic Acidemia involves reducing protein intake, particularly the amino acids Valine, Isoleucine, Methionine, and Threonine that feed into the defective pathway. This requires placing the infant on a special metabolic formula depleted in these amino acids. Until the diagnosis of Propionic Acidemia is clearly established, all patients should be given a trial of cobalamin and biotin to evaluate a response. Carnitine supplementation has proven beneficial. Oral antibiotics help control infections and hypothetically reduce intestinal bacteria, which produce propionic acid that can be absorbed through the gut and contribute to metabolic stress. Prevention of constipation is important. Strict control is most crucial throughout childhood. Rarely, older patients with mild forms of PA are reported to function untreated.

Because the diagnosis and therapy of metabolic disorders like PA is complex, the pediatrician is advised to manage the patient in close collaboration with a consulting pediatric metabolic disease specialist. It is recommended that parents travel with a letter of treatment guidelines from the patient’s physician.

Complications

Complications of Acidemia (Propionic)
The list of complications that have been mentioned in various sources for Acidemia, isovaleric includes:

1. Coma