Primary carnitine deficiency and cardiomyopathy

Abstract

Carnitine is essential for the transfer of long-chain fatty acids from the cytosol into mitochondria for subsequent β-oxidation. A lack of carnitine results in impaired energy production from long-chain fatty acids, especially during periods of fasting or stress. Primary carnitine deficiency (PCD) is an autosomal recessive disorder of mitochondrial β-oxidation resulting from defective carnitine transport and is one of the rare treatable etiologies of metabolic cardiomyopathies. Patients affected with the disease may present with acute metabolic decompensation during infancy or with severe cardiomyopathy in childhood. Early recognition of the disease and treatment with L-carnitine may be life-saving. In this review article, the pathophysiology, clinical presentation, diagnosis, treatment and prognosis of PCD are discussed, with a focus on cardiac involvements.

Keywords: Cardiomyopathies; Carnitine deficiency, primary.

Fig. 1

The role of carnitine in the transport of mitochondrial long-chain fatty acid oxidation. Carnitine is actively transported via OCTN2 into the cytoplasm and forms ester bonds with long chain carboxylic acids by the action of carnitine palmitoyl transferase I (CPT I), located in the inner aspect of the outer mitochondrial membrane. Acylcarnitine is then translocated across the inner mitochondrial membrane by the carnitine acylcarnitine translocase (CACT) and cleaved by CPT II in the inner aspect of the inner mitochondrial membrane. Carnitine is released in the mitochondrial matrix and then return to the cytoplasm for another cycle, while the fatty acids are conjugated back to coenzyme A in the mitochondrial matrix and then enter the pathway of β-oxidation and ketone synthesis. FATP: fatty acid transport protein.

Fig. 2

Electrocardiographic tracing before and after treatment with L-carnitine. A: before treatment, showing a shortened QT interval (QTc 330 msec) associated with an abnormally tall and symmetrical peaking T wave. B: after one-month L-carnitine therapy, T-wave amplitude and QT interval (QTc 401 msec) return to normal.

Fig. 3

Transthoracic echocardiography before and after treatment with L-carnitine. A: M-mode echocardiogram demonstrating a severely enlarged left ventricle (LVEDD 5.40 cm) with poor systolic function (LVEF 40.6%) on initial examination (study). B: after five-month L-carnitine therapy, the left ventricle return to normal size (LVEDD 3.09 cm) and systolic function (LVEF 65.9%). LVEF: left ventricular ejection fraction, LVEDD: left ventricular end-diastolic diameter.