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. Conclusion: 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.
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Abbreviations
- ADHS:
-
Attention deficit and hyperactivity syndrome
- DCM:
-
Dilated cardiomyopathy
- ECG:
-
Electrocardiography
- PA:
-
Propionic acidemia
- PCCA and PCCB:
-
Propionyl-CoA carboxylase subunits A and B
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Acknowledgments
This work has been supported by radiz—Rare Disease Initiative Zurich, a clinical research priority program of the University of Zurich. We would like to thank Corinne Britschgi and Seraina Lutz for technical support with molecular genetic analysis of PCCB gene and PCC activity assays, respectively.
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Communicated by Beat Steinmann
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Laemmle, A., Balmer, C., Doell, C. et al. Propionic acidemia in a previously healthy adolescent with acute onset of dilated cardiomyopathy. Eur J Pediatr 173, 971–974 (2014). https://doi.org/10.1007/s00431-014-2359-6
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DOI: https://doi.org/10.1007/s00431-014-2359-6