Genetics of Propionic Acidemia (Propionyl CoA Carboxylase Deficiency) Workup

Updated: Feb 18, 2019
  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Laboratory Studies

Expanded newborn metabolic screening techniques involving tandem mass spectrometry include propionic acidemia among the several organic acidemias that pose an immediate threat to the survival of the neonate.

A basic metabolic panel is indicated in propionyl coenzyme A (CoA) carboxylase deficiency (ie, propionic acidemia). Serum electrolyte measurement is important. A child who is feeding poorly and vomits may have significant electrolyte abnormalities. Accumulation of free organic acids (anions) significantly increases the anion gap (see the Anion Gap calculator). Therefore, an anion gap larger than 16 mEq/L may indicate propionic acidemia. On rare occasions, affected babies do not present with an increased anion gap.

Because free propionic acid is known to suppress bone marrow, assessing the status of circulating elements, including platelets, is important.

Specific gravity, obtained through a routine urinalysis, is important in assessing the degree of dehydration. The presence of ketones in association with an anion gap (as mentioned above) is strongly suggestive of ketoacidosis. A low urine pH lends additional weight to this suspicion.

Obtaining blood ammonia levels is important in the assessment of the overall metabolic status of the patient, as well as to help in determination of causes for mental status changes. Blood ammonia levels are often secondarily elevated.

Obtaining plasma lactate levels is helpful in the determination of the causes for an observed anion gap. Lactate levels are often elevated but are not sufficiently high enough to account for the increase in anion gap, which should then prompt further investigation.

Assessing the urinary organic acid levels is the definitive clinical diagnostic study. Most frequently, it demonstrates large increases in beta-hydroxy propionic acid, lactic acid, and methylcitrate excretion levels.

Leukocyte propionyl CoA carboxylase activity is the study required for definitive biochemical diagnosis and appropriate genetic counseling.

Mutation analysis has provided additional insight into the nature of the many mutations reported; at least one study suggests the need for additional investigation beyond routine analysis in the identification of several subtle genomic abnormalities in PCCA mutational analysis. [16, 17]


Other Tests

ECG is recommended with annual 24-hour Holter monitoring in all patients because of the frequency of prolonged QTc intervals and decreased left ventricular contractility reported in patients with propionic acidemia.

Further evaluation with continuous ECG monitoring and echocardiography should be considered. Cardiomyopathy, both hypertrophic and dilated, is frequently seen in these individuals, requiring close follow-up, including an annual echocardiogram. Moreover, any sign of early heart failure (ie, poor growth, tachycardia, tachypnea [which can be confused with developing metabolic acidosis]) should trigger such an investigation.

Annual examination by an ophthalmologist is recommended, with careful examination of the anterior chamber and fundus due to a high risk of optic atrophy. [18, 14, 15]


Histologic Findings

A diagnosis of propionic acidemia that is missed in life is extremely difficult to make postmortem.