Carnitine acylcarnitine translocase deficiency

A. A. M. Morris, S. I. Olpin, M. Brivet, et al. A patient with carnitine-acylcarnitine translocase deficiency with a mild phenotype. Journal of Pediatrics 132, 514 (1998). 

Carnitine-acylcarnitine translocase deficiency Carnitine palmitoyltransferase type II deficiency 2... 

Defects of fatty acid catabolism, with the exception of SCAD deficiency, generally have elevation of more than one characteristic metabolite. MCAD deficiency is characterized by accumulation of C6, C8 (mainly) and C10 l species. LCAD and VLCAD are characterized by accumulation of C14 l, C14 2 and (usually) C16 and C18 l species. LCHADD and TFP deficiencies are characterized by the accumulation of OH-C16, 0H-C18 1 and usually at least one of the other long-chain species C14 1, C16 and C18 l. The CPT-II and CAT (carnitine/acylcarnitine translocase) deficiencies are characterized by marked elevation of both C16 and C18 1, but not C14 1. Multiple acyl-CoA deficiency (MAD) has several different etiologies, including electron transferring protein (ETF) deficiency, ETF-dehydrogenase deficiency and riboflavin deficiency. Disease patterns vary considerably. In severe forms of the disorder, a generalized marked elevation of mxiltiple intermediates is observed. CPT-I should be suspected when both C16 and Cl8 1 are very low in whole blood, especially if free carnitine is normal or elevated. 

DJ., Heymans, H.S.A. Smit, G.P. (1995) J. Inker. Metab. Dis., 18, 230-232. A patient with lethal cardiomyopathy and a carnitine-acylcarnitine translocase deficiency. 

J Inherit Metab Dis 20 714-715. Carnitine-acylcarnitine translocase deficiency—a mild phenotype. 

Pande, S.V., Brivet, M., Slama, A., Demaugre, R, Aufrant, C. Saudubray, J.M. (1993). J Clin Invest 91 1247-1252. Carnitine-acylcarnitine translocase deficiency with severe hypoglycemia and auriculo ventricular block. Translocase assay in permeabilized fibroblasts. 

Roschinger W, Muntau AC, Duran M, Dorland L, IJlst L, Wanders RJ et al. Carni-tine-acylcarnitine translocase deficiency metabolic consequences of an impaired mitochondrial carnitine cycle. Clin Chim Acta 2000 298 55-68. 

Stanley, C.A., Hale, D.E., Berry, G.T., Deleeuw, S., Boxer, J. Bonnefont, J.P. (1992). N EnglJ Med 327 19-23. Brief report a deficiency of carnitine-acylcarnitine translocase in the inner mitochondrial membrane. 

The answer is b. (Murray, pp 505-626. Scriver, pp 4029-4240. Sack, pp 121-138. Wilson, pp 287-320.) A deficiency in carnitine, carnitine acyl-transferase 1, carnitine acyltransferase 11, or acylcarnitine translocase can lead to an inability to oxidize long-chain fatty acids. This occurs because all of these components are needed to translocate activated long-chain (>10 carbons long) fatty acyl CoA across mitochondrial inner membrane into the matrix where P oxidation takes place. Once long-chain fatty acids are coupled to the sulfur atom of CoA on the outer mitochondrial membrane, they can be transferred to carnitine by the enzyme carnitine acyltransferase I, which is located on the cytosolic side of the inner mitochondrial membrane. Acyl carnitine is transferred across the inner membrane to the matrix surface by translocase. At this point the acyl group is reattached to a CoA sulfhydryl by the carnitine acyltransferase 11 located on the matrix face of the inner mitochondrial membrane. 

---