UNLABELLED: 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.
UNLABELLED: 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.
Authors: Sarah C Grünert; Stephanie Müllerleile; Linda De Silva; Michael Barth; Melanie Walter; Kerstin Walter; Thomas Meissner; Martin Lindner; Regina Ensenauer; René Santer; Olaf A Bodamer; Matthias R Baumgartner; Michaela Brunner-Krainz; Daniela Karall; Claudia Haase; Ina Knerr; Thorsten Marquardt; Julia B Hennermann; Robert Steinfeld; Skadi Beblo; Hans-Georg Koch; Vassiliki Konstantopoulou; Sabine Scholl-Bürgi; Agnes van Teeffelen-Heithoff; Terttu Suormala; Wolfgang Sperl; Jan P Kraus; Andrea Superti-Furga; Karl Otfried Schwab; Jörn Oliver Sass Journal: Orphanet J Rare Dis Date: 2013-01-10 Impact factor: 4.123
Authors: Nicholas M McCrory; Mathew J Edick; Ayesha Ahmad; Susan Lipinski; Jessica A Scott Schwoerer; Shaohui Zhai; Kaitlin Justice; Cynthia A Cameron; Susan A Berry; Loren D M Pena Journal: J Pediatr Date: 2016-10-21 Impact factor: 4.406
Authors: Moniek Riemersma; Mark R Hazebroek; Appolonia T J M Helderman-van den Enden; Gajja S Salomons; Sacha Ferdinandusse; Martijn C G J Brouwers; Liesbeth van der Ploeg; Stephane Heymans; Jan F C Glatz; Arthur van den Wijngaard; Ingrid P C Krapels; Jörgen Bierau; Han G Brunner Journal: Eur J Hum Genet Date: 2017-08-30 Impact factor: 4.246