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Cardiac manifestations in disorders of fat and carnitine metabolism in infancy
T Ino1, W G Sherwood, L N Benson
1Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Abnormal carnitine metabolism can cause both hypertrophic and dilated cardiomyopathy in children. Early diagnosis and L-carnitine supplementation may improve cardiac function in these patients.
Area of Science:
- Cardiology
- Metabolic Disorders
- Pediatrics
Background:
- Hypocarnitinemia, a condition of low carnitine levels, has an uncertain prognosis in pediatric cardiomyopathy.
- Abnormal carnitine metabolism is implicated in various forms of heart muscle disease.
Purpose of the Study:
- To evaluate cardiac hemodynamics, histology, and response to L-carnitine therapy in children with cardiomyopathy and abnormal carnitine metabolism.
- To investigate the relationship between different types of carnitine deficiency and cardiomyopathy presentation.
Main Methods:
- Retrospective analysis of 11 children with cardiomyopathy and abnormal carnitine metabolism.
- Evaluation of clinical data, echocardiography, electrocardiography, and histological findings.
- Assessment of response to oral L-carnitine replacement therapy over 3 months to 2 years.
Main Results:
- Both hypertrophic (6 children) and dilated (5 children) cardiomyopathy were observed.
- Histological examination revealed significant lipid accumulation in myocytes.
- Six of eight patients receiving L-carnitine therapy showed echocardiographic improvement.
Conclusions:
- Abnormal carnitine metabolism is a significant cause of pediatric cardiomyopathy, presenting as either hypertrophic or dilated forms.
- Measuring plasma carnitine and fatty acid by-products is crucial for diagnosing carnitine-related cardiomyopathy.
- Carnitine supplementation can lead to improved cardiac function in affected children.
Abstract:
The prognosis of patients with cardiomyopathy associated with hypocarnitinemia is uncertain. Cardiac hemodynamics, histologic findings and response to oral L-carnitine therapy were retrospectively evaluated in 11 children with cardiomyopathy associated with abnormal carnitine metabolism. Three had systemic carnitine deficiency, two familial hypocarnitinemia with neutropenia, three transient neonatal hypocarnitinemia and three a carnitine insufficiency syndrome. Six had a hypertrophic and five a dilated cardiomyopathy. Hypotonia was present in seven (64%). The cardiothoracic ratio was greater than 0.60 in eight (73%). The most frequent abnormality on the electrocardiogram was ST-T wave inversion in the left precordial leads with various degrees of left ventricular hypertrophy. Echocardiographically, two patients with hypertrophic cardiomyopathy had decreased left ventricular function and two patients with dilated cardiomyopathy had increased thickness of the left ventricular wall. Histologic evaluation (two autopsies and one endomyocardial biopsy) revealed striking lipid accumulation within hypertrophied myocytes. Six of eight patients on carnitine replacement therapy had improvement echocardiographically during a 3 month to 2 year follow-up period. In summary, both hypertrophic and dilated cardiomyopathy can result from abnormal carnitine metabolism. The determination of plasma carnitine concentrations and fatty acid metabolism by-products should be performed in all patients with either form of cardiomyopathy of unknown etiology because carnitine supplementation may lead to improvement.