Dr Ira Shah
MD, DCH (Gold Medalist), FCPS, DNB

one-year female child (only child) born of third degree consanguineous marriage presented with fever and cough since 4 days and breathlessness since 2 days. She had history of recurrent cough, fever and breathlessness since 6 months. On examination, she had tachycardia with heart rate of 160 beats/min and peripheral pulses were feeble. Her respiratory rate was 36/min and blood pressure was low (90/50 mm of Hg). On systemic examination, she had cardiomegaly and heart sounds were muffled with no evidence of murmur. Other systemic examination revealed hepatomegaly. She was diagnosed to be in congestive cardiac failure and suspected to have myocarditis or cardiomyopathy. Her X-ray chest revealed cardiomegaly with increased pulmonary blood flow. A 2D Echo showed non-compacted left ventricle leading to dilated cardiomyopathy. There was evidence of spongy myocardium with Fractional shortening of 10-12% and ejection fraction of 22% with a moderate MR. In view of the 2D Echo findings, a differential diagnosis of inherited cardiomyopathies, BAART syndrome, and inborn errors of metabolism was considered. Both the parents underwent a 2D Echo, which was normal ruling out inherited cardiomyopathy & Barth syndrome. Her S. carnitine was low (2%) and urine dicarboxylic acid was negative. Her blood gases showed metabolic acidosis with bicarbonate of 13.9 MEq/L. She had hyperammonemia [S. NH3 = 218 mcg/dl (Normal = 30-90 mcg/dl)] but her urinary aminoacidogram and plasma aminoacidogram were normal. Her CPK levels and SGOT were normal though serum LDH was slightly elevated [268 IU/L]. Thus, she was diagnosed as carnitine deficiency and treated with ionotropes, vasodilators and carnitine (100mg/kg/day). After 5 days of carnitine, her ejection fraction improved to 36% and Fractional Shortening was 18% and was discharged. After 15 days, the patient was readmitted with fever and cough since 2 days. X-Ray chest showed cardiomegaly and left sided consolidation. Her ejection fraction was 36% and fractional shortening was 60% and her cardiac enzymes (S. CPK, LDH, SGOT) were normal. She was treated with Dobutamine and Intravenous antibiotics. However, the pneumonia worsened and the child died after 5 days.

Primary carnitine deficiency (Plasma Membrane Carnitine Transport Defect) is the only genetic defect in which carnitine deficiency is the cause, rather than the consequence of impaired fatty acid oxidation. Patients present with progressive cardiomyopathy at 2-4 years of age with or without skeletal muscle weakness. Infants may have fasting hypoketotic hypoglycemia. The defect is in the plasma membrane sodium dependent carnitine transporter present in the heart, muscle and kidney. This transporter maintains the intracellular carnitine 20 to 50 times higher than plasma concentrations. Patients have extremely reduced carnitine levels in plasma and muscle (1-2% of normal). It is an autosomal recessive disorder and heterozygote parents have plasma levels of carnitine approximately 50% of normal. The fasting urinary organic acid profile may show a hypoketotic dicarboxylic aciduria if hepatic fatty acid oxidation is impaired. The defect in carnitine transport can be demonstrated in vitro by assay of carnitine uptake using cultured fibroblasts or lymphoblasts. Treatment consists of oral carnitine (50-100 mg/kg/day) in pharmacologic doses and it corrects the cardiomyopathy & muscle weakness.