The syndrome of systemic carnitine deficiency

Abstract

An 11 -year-old boy had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped musculature. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. Hypertrophied smooth endoplasmic reticulum and excessive microbodies were present in liver. Marked carnitine deficiency was shown in skeletal muscle, plasma, and liver. Ketogenesis was impaired on a high fat diet, but omega oxidation of fatty acids was enhanced. There was excessive glucose uptake and essentially no oxidation of labeled long-chain fatty acids by perfused forearm muscles in vivo. Oral replacement therapy restored plasma carnitine levels to normal, but not liver or muscle carnitine levels, and was accompanied by clinical improvement.The syndrome of systemic carnitine deficiency Clinical, morphologic, biochemical, and pathophysiologic features n 1972 Engel and Siekert described an unusual I variety of lipid storage myopathy in a 24-year-old woman. * The unusual features included a striking beneficial response to corticosteroid therapy and the c o e x i s t e n c e of a b n o r m a l l i v e r f u n c t i o n t e s t s . Subsequently, Engel and Angelini found that the skeletal muscle of this patient had a very low level of carnitine, and in vifro oxidation of fatty acids by her muscle was considerably reduced. 2 -3 This patient was the first recognized human example of carnitine deficiency. Since that report, at least four other patients have been identified. [4][5][6][7] This paper is a detailed report of a patient with systemic carnitine d e f i~i e n c y ,~ with special attention to the vaned clinical, morphologic, biochemical, and metabolic features of this disorder. Dr. Karpati's address is Montreal Neurological Institute, 3801 University St., Montreal, Que., Canada H3A 284.Case report. This 1 1-year-old boy was born after a full term uneventful pregnancy and delivery. Birth weight was 7 Ib. Milestones of his psychomotor development were normal, but according to his mother, he was always a "weak and clumsy child" and his neck and head were always "floppy."At age three and one-half years, the patient was hospitalized with acutely developing vomiting and a major convulsive seizure. Cerebrospinal fluid was normal, as was serum calcium. His blood sugar was reduced initially to 27 mg percent but subsequently was found to be normal on several occasions. He had some abnormal liver function tests; serum glutamic oxaloacetic transaminase (SGOT) 103 units (normal, less than 30) and serum glutamic pyruvic transaminase (SGPT) 125 units (normal, less than 1 5 units), but serum bilirubin was normal. An electroencephalogram (EEG) showed a diffuse, high amplitude dysrhythmia. The cause of the acute encephalopathy and the abnormal liver function tests was not established and the child's clinical status, EEG, and liver function tests returned to normal.The patient started school at age six, but after completing grades 1 and 2 he had difficulties with writing and spelling. Psychometric evaluation reveal...

Hypoglycemia, Hepatic Dysfunction, Muscle Weakness, Cardiomyopathy, Free Carnitine Deficiency and Long-Chain Acylcarnitine Excess Responsive to Medium Chain Triglyceride Diet

“…Ala, alanine ALT, alanine aminotransferase AST, aspartate aminotransferase CPK, creatine kinase hGH, human growth hormone LA, left atrium LPEP/LVET, left pre-ejection period/left ventricular ejection time P-OHB, beta-hydroxybutyrate RPEP/RVET, right pre-ejection period/right ventricular ejection time LVED, left ventricular end diastolic dimension LVES, left ventricular end systolic dimension MCT, medium chain triglyceride PC, pyruvate carboxylase PEPCK, phosphoenol phosphate carboxykinase U, units Hepatic long-chain acyl CoA carnitine transferase deficiency (4), multiple acyl CoA dehydrogenase deficiency (glutaric aciduria type 11) (18), and systemic carnitine deficiency (3,9,12,17,24,37,43), all of which are associated with impaired fatty acid oxidation, have hypoglycemia as a major clinical manifestation.…”

Managing liver dysfunction in parenteral nutrition

“…Carnitine is involved in the transport of long-chain fatty acids across the mitochondrial membrane so that they can undergo oxidation. In deficiency states in which carnitine levels are very low (<10% normal levels) hepatic steatosis can develop (35) . Although plasma carnitine levels are low in patients receiving parenteral nutrition, they are about 50% normal levels and so considerably higher than levels in patients with congenital or acquired deficiency (30,31,35) .…”

“…In deficiency states in which carnitine levels are very low (<10% normal levels) hepatic steatosis can develop (35) . Although plasma carnitine levels are low in patients receiving parenteral nutrition, they are about 50% normal levels and so considerably higher than levels in patients with congenital or acquired deficiency (30,31,35) . There is limited evidence to suggest an inverse relationship between carnitine levels and ALP in patients receiving parenteral nutrition (36) .…”

Metabolic and nutritional considerations in nonalcoholic fatty liver

“…In primary carnitine deficiency, in which tissue concentrations may fall to 10% to 20% of normal, fatty liver is a common clinical finding. 65 In secondary carnitine deficiency, abnormally low concentrations of carnitine, albeit not as low as those present in primary carnitine deficiency, occur secondary to defects in intermediary metabolism, certain diseases, drug reactions, and impaired nutritional conditions such as kwashiorkor. 66,67 Because the major sources of carnitine come from de novo synthesis from the essential amino acids lysine and methionine, as well as from dietary sources such as meats and dairy products, low carnitine concentrations in kwashiorkor are probably related to deficient protein intake.…”