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

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          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.

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          Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients

          Background Propionic acidemia is an inherited disorder caused by deficiency of propionyl-CoA carboxylase. Although it is one of the most frequent organic acidurias, information on the outcome of affected individuals is still limited. Study design/methods Clinical and outcome data of 55 patients with propionic acidemia from 16 European metabolic centers were evaluated retrospectively. 35 patients were diagnosed by selective metabolic screening while 20 patients were identified by newborn screening. Endocrine parameters and bone age were evaluated. In addition, IQ testing was performed and the patients’ and their families’ quality of life was assessed. Results The vast majority of patients (>85%) presented with metabolic decompensation in the neonatal period. Asymptomatic individuals were the exception. About three quarters of the study population was mentally retarded, median IQ was 55. Apart from neurologic symptoms, complications comprised hematologic abnormalities, cardiac diseases, feeding problems and impaired growth. Most patients considered their quality of life high. However, according to the parents’ point of view psychic problems were four times more common in propionic acidemia patients than in healthy controls. Conclusion Our data show that the outcome of propionic acidemia is still unfavourable, in spite of improved clinical management. Many patients develop long-term complications affecting different organ systems. Impairment of neurocognitive development is of special concern. Nevertheless, self-assessment of quality of life of the patients and their parents yielded rather positive results.
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            Cardiomyopathies in propionic aciduria are reversible after liver transplantation.

            To evauluate the relationship between propionic acidemia (PA) and cardiomyopathy. We retrospectively compared clinical and metabolic results of patients with PA with and without cardiomyopathy. Of 26 patients with PA who survived the first year of age, a dilated cardiomyopathy developed in 6 (group 1) at a median age of 7 years (range, 5-11 years). They were compared with 14 patients without cardiomyopathy for whom data were available (group 2). Their median age at the time of the study was 11 years (range, 3-21 years). PA was diagnosed in the neonatal period in 5 of 6 patients in group 1 and 11 of 14 patients in group 2. All patients received similar medical treatment. Two patients in group 1 died of cardiac arrest. In 2 patients, the cardiomyopathy was reversed during the year after orthotopic liver transplantation (OLT). In 2 other patients, OLT was contraindicated because of severe heart disease. The number of metabolic distress episodes was similar in both groups. Excretion of propionate metabolites in urine did not correlate with the occurrence of cardiomyopathy. Dilated cardiomyopathy, a frequent complication of PA, develops independent of any specific metabolic profile and is reversible after OLT.
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              Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia.

              To investigate electrophysiological and functional signs of myocardial damage in patients with propionic acidemia (PA), an inborn error of metabolism caused by deficiency of propionyl CoA carboxylase (PCC). In an observational longitudinal study 10 patients with PA (6 boys and 4 girls) ranging between 2.5 and 20.2 (median 9.0) years of age at last follow-up were investigated over a period of up to 20 (mean 7.4) years using 12-lead electrocardiograms (ECGs), 24-hour continuous ECG recordings, bicycle exercise testings, and echocardiography with special focus on repolarization abnormalities such as corrected QT interval (QTc) prolongation, ventricular dysrhythmias, and left ventricular systolic function. QTc interval was prolonged (>440 ms) in 70% of patients beyond infanthood. Continuous ECG recordings revealed rhythm disturbances in 20% of patients. M-mode echocardiographic left ventricular function was reduced (fractional shortening [FS] <30%) in 40%. One patient showed signs of dilated cardiomyopathy. The majority of patients with PA (even in clinically stable situations) have disturbances in cardiac electrophysiology that can contribute to cardiac complications. Possible mechanisms include effects of toxic metabolites or deprivation of essential substrates. To avoid life-threatening complications, we recommend regular cardiological evaluations in this group of patients.
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                Author and article information

                Journal
                European Journal of Pediatrics
                Eur J Pediatr
                Springer Nature
                0340-6199
                1432-1076
                July 2014
                June 2014
                : 173
                : 7
                : 971-974
                Article
                10.1007/s00431-014-2359-6
                24916042
                841933e3-b2cc-4597-810d-d17e34be014f
                © 2014
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