Genetics of Propionic Acidemia (Propionyl CoA Carboxylase Deficiency) Clinical Presentation
- Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD more...
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- Many infants with propionyl coenzyme A (CoA) carboxylase deficiency (ie, propionic acidemia) initially present in the first month of life, often with failure to thrive due to feeding intolerance and vomiting. Somnolence is also often a part of the history; thus, poor feeding may be erroneously attributed to CNS disorders.
- Other infants have a fulminant initial presentation, with rapidly developing ketoacidosis, dehydration, shock, and a precedent history of lethargy, poor feeding, and rapid breathing that only extends over 1-2 days.
- As a rare autosomal recessive disease, a family history of similarly affected infants is extremely unlikely.
- Occasionally, an older infant or young child may have a lifelong history of episodic lethargy, anorexia, vomiting, and acidosis that has responded to short hospital stays with intravenous glucose and bicarbonate administration.
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- Affected newborns have been protected from their disease by the maternal circulation and metabolism; therefore, no relevant physical findings present upon neonatal examination.
- Carefully assess infants who present with unexplained vomiting for signs of ketoacidosis; urinalysis is particularly important because neonates normally do not excrete large quantities of ketones.
- CNS depression, which signifies either severe acidosis or hyperammonemia, may be apparent upon examination.
- Any infant with an inborn error can also be affected by other disorders. Suspicion of sepsis based on the typical nonspecific signs must not eliminate the possibility of underlying disease, such as propionic acidemia, from the differential.
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- Propionyl CoA carboxylase is a tetrameric enzyme, comprising 4 chains of 2 α and 2 β polypeptides.
- The gene for production of the β chain has a locus of 13q32, whereas the gene for production of the β chain has a locus of 3q21-q22. Thus, a mutation at either locus affects enzyme activity, but only changes that have occurred in either the α or the β chain affect the respective enzyme activity.
- In a mixed heterozygotic individual, with mutations at each gene locus, both types of monomeric constituent polypeptides are affected.
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