title: Propionic acidemia in a previously healthy adolescent with acute onset of dilated cardiomyopathy.
abstract: Propionic acidemia (PA) is a rare autosomal recessive organic aciduria resulting from defects in propionyl-CoA-carboxylase (PCC), a key enzyme of intermediate energy metabolism. PA mostly manifests during the neonatal period, when affected newborns develop severe metabolic acidosis and hyperammonemia. We present a previously healthy teenager, who suffered from acute fatigue and breathlessness. The patient was tachycardic, displayed a precordial heave and a systolic murmur. Cardiac investigations revealed severe dilated cardiomyopathy (DCM). Biochemical work up led to the diagnosis of PA. Remarkably, this patient of consanguineous Hispanic origin was in a good general health condition before the acute onset of DCM. Diagnosis of PA was confirmed by enzymatic and molecular genetic analysis, the latter revealing a novel homozygous mutation in the PCCB gene (c.1229G > A; p.R410Q). Residual PCC enzyme activity of approximately 14 % of normal was detected in patient's lymphocytes and fibroblasts, thereby providing a possible explanation for the hitherto asymptomatic phenotype.
  
  
  CONCLUSIONS
  Isolated DCM, although rare, can be the leading and/or sole symptom of late-onset PA. Therefore, patients with DCM should receive a comprehensive diagnostic evaluation including selective screening for inborn errors of metabolism.
authors.affiliation: Division of Metabolic Diseases, University Children`s Hospital, Zurich, Switzerland, alexander.laemmle@kispi.uzh.ch.
authors.forename: Alexander
authors.initials: A
authors.lastname: Laemmle
authors.forename: Christian
authors.initials: C
authors.lastname: Balmer
authors.forename: Carsten
authors.initials: C
authors.lastname: Doell
authors.forename: Jörn Oliver
authors.initials: JO
authors.lastname: Sass
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Baumgartner
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D019735:Carbon-Carbon Ligases / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000201:enzymology; D003241:Consanguinity; D004452:Echocardiography; D006801:Humans; D008297:Male; D009154:Mutation; D056693:Propionic Acidemia / Q000175:diagnosis* / Q000201:enzymology
chemical_list: D019735:Carbon-Carbon Ligases; C022458:propionyl CoA carboxylase (ATP-hydrolyzing)