Propionic acidemia in a previously healthy adolescent with acute onset of dilated cardiomyopathy

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• 作者：Alexander Laemmle (1) (5)
  Christian Balmer (2) (5)
  Carsten Doell (3)
  J?rn Oliver Sass (4) (5)
  Johannes H?berle (1) (5)
  Matthias R. Baumgartner (1) (5)
  
• 关键词：Propionic acidemia ; Dilated cardiomyopathy ; Propionyl ; CoA carboxylase ; Organic aciduria
• 刊名：European Journal of Pediatrics
• 出版年：2014
• 出版时间：July 2014
• 年：2014
• 卷：173
• 期：7
• 页码：971-974
• 全文大小：
• 参考文献：1. Baumgartner D, Scholl-Bürgi S, Sass JO, Sperl W, Schweigmann U, Stein JI, Karall D (2007) Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia. J Pediatr 150:192-97 CrossRef
  2. Fenton WA, Gravel RA, Rosenblatt DS (2001) Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet A, Sly W, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill, New York, pp 2165-190
  3. Gallego-Villar L, Perez-Cerda C, Perez B, Abia D, Ugarte M, Richard E, Desviat LR (2012) Functional characterization of novel genotypes and cellular oxidative stress studies in propionic acidemia. J Inherit Metab Dis 36:731-40 CrossRef
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• 作者单位：Alexander Laemmle (1) (5)
  Christian Balmer (2) (5)
  Carsten Doell (3)
  J?rn Oliver Sass (4) (5)
  Johannes H?berle (1) (5)
  Matthias R. Baumgartner (1) (5)
  
  1. Division of Metabolic Diseases, University Children`s Hospital, Zurich, Switzerland
  5. Children’s Research Center, University Children`s Hospital, Zurich, Switzerland
  2. Division of Cardiology, University Children`s Hospital, Zurich, Switzerland
  3. Division of Neonatology and Paediatric Intensive Care, University Children`s Hospital, Zurich, Switzerland
  4. Division of Clinical Chemistry & Biochemistry, University Children`s Hospital, Zurich, Switzerland
  
• ISSN：1432-1076

文摘

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-gt;?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.