Carnitine deficiency, systemic

L-Carnitine (4-trimethylamino-3-hydroxybutyric acid) is necessary for the mitochondrial jS-oxidation of long-chain fatty acids which are converted from their acyl-CoA esters into the corresponding carnitine esters for transport through the inner mitochondrial membrane. Thus in carnitine deficiency, jS-oxidation of long-chain fatty acids becomes impaired, leading to their 

Jamaican vomiting sickness is characterized biochemically by profound hypoglycaemia, acidosis without ketosis, and post-mortem by extensive diffuse fatty degeneration of liver and kidneys with small droplet infiltration closely similar to that observed in patients with Reye s syndrome (Section 14.4.2). 

Glycogen deposits are also depleted. Treatment sufficiently early and rapidly with intravenous glucose is effective (Jelliffe and Stuart, 1954) and with education through public health programmes, the occurrence of the disorder has greatly diminished (Miller, 1973 Stuart, 1974). The disorder, and mode of action of hypoglycin, remain of considerable interest, however, particularly with the close similarities to Reye s syndrome and to two other cases of vomiting sickness probably due to the effects of a toxin (Section 14.4.2). 

2 Twin English siblings with non-ketotic dicarboxylic aciduria, features of Reye s syndrome and with close similarities to Jamaican vomiting sickness (organic aciduria, hypoglycaemia, diarrhoea and vomiting, acidosis without ketosis) 

Chalmers et al. (1977, 1980) reported 17-month-old identical Caucasian male twins in England who developed vomiting and diarrhoea, coma and convulsions. Both children were admitted to hospital 30 h after the onset of symptoms, one being dead on arrival. The second sibling was comatose with undetectable blood glucose, but made a complete recovery after being 

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Lahjouji, K., G. A. Mitchell, and I. A. Qureshi. Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol. Genet. Metab. 2001, 73, 287-297. 

Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nature Genet 1999 21(1) 91 94. 

Mayatepek E, Nezu J, Tamai I, Oku A, Katsura M, Shimane M et al. Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency. Hum Mutat 2000 15(1) 118. 

Vaz FM, Scholte HR, Ruiter J, Hus-saarts-Odijk FM, Pereira RR, Schweitzer S et al. Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency. Hum Genet 1999 105 (1/2) 157-161. 

Glutaric aciduria type II, which is a defect of P-oxida-tion, may affect muscle exclusively or in conjunction with other tissues. Glutaric aciduria type II, also termed multiple acyl-CoA dehydrogenase deficiency (Fig. 42-2), usually causes respiratory distress, hypoglycemia, hyperammonemia, systemic carnitine deficiency, nonketotic metabolic acidosis in the neonatal period and death within the first week. A few patients with onset in childhood or adult life showed lipid-storage myopathy, with weakness or premature fatigue [4]. Short-chain acyl-CoA deficiency (Fig. 42-2) was described in one woman with proximal limb weakness and exercise intolerance. Muscle biopsy showed marked accumulation of lipid droplets. Although... 

J. Nezu, I. Tamai, A. Oku, R. Ohashi, H. Yabuuchi, N. Hashimoto, H. Nikaido, Y. Sai, A. Koizumi, Y. Shoji, G. Takada, T. Matsuishi, M. Yoshino, H. Kato, T. Ohura, G. Tsujimoto, J. Hayakawa, M. Shimane, and A. Tsuji. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 21 91-94 (1999). 

The second section of the book is Fuel Metabolism and Energetics. Important pathways and enzymes involved in fuel utilization are discussed in the chapters Pyruvate Dehydrogenase Complex Deficiency Mitochondrial En-cephalomyopathy, and Systemic Carnitine Deficiency. The role of gluconeogenesis in glucose homeostasis is illustrated by a discussion in the chapter Neonatal Hypoglycemia. 

Lahjouji. K., Mitchell, G.A., and Qureshi, l.A. (2001) Carnitine transport by organic cation tr ansporters and systemic carnitine deficiency. Molecular Genetics and Metabolism. 73 (4), IXl-lSn. 

SLC22 Organic cation/anion/zwitterion transporter 18 Pravastatin, metformin Systemic carnitine deficiency syndrome... 

Once carnitine is produced, the intracellular homeostasis is controlled by different membrane transporters called organic cation transporters (OCTNs), specifically OCTN2. OCTN2 acts to operate on both the intestinal and renal absorption of L-camitine, in addition to playing a major role in tissue distribution and transport rates within circulation. This transporter has been implieated in the deficiencies mentioned earlier in this chapter, as research has shown that OCTN2 is directly inhibited by various agents and substances identified as eausing systemic carnitine deficiencies. ... 

Engel, A.G., ReBouche, C.J., Wilson, D.M., Glasgow, A.M., Romshe, C.A., and Cruse, R.P., Primary systemic carnitine deficiency. 11. Renal handling of carnitine. 

Ware, A.J., Burton, W.C., McGarry, J.D., Marks, J.F., and Weinburg, A.G., Systemic carnitine deficiency. Report of a fatal case with multisystemic manifestations. J. Pediatr, 93, 959-962, 1978. 

Glasgow, A.M., Eng, G. and Engel, A.G. (1980), Systemic carnitine deficiency simulating recurrent Reye syndrome. J. Pediatr., 96,889. 

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