Journal of Lipid Research, Vol 31, 335-340, Copyright © 1990 by Lipid Research, Inc.

ARTICLES

Biochemical and clinical analysis of accumulated glycolipids in symptomatic heterozygotes of angiokeratoma corporis diffusum (Fabry's disease) in comparison with hemizygotes

I Hozumi, M Nishizawa, T Ariga and T Miyatake
Department of Neurology, Niigata University, Japan.

Angiokeratoma corporis diffusum (Fabry's disease) is an X-linked disorder of glycosphingolipid catabolism. Heterozygous females, although usually asymptomatic, are occasionally as severely afflicted as hemizygous males; recently we identified a heterozygous patient with cardiomyopathy and severe pain in the extremities. In order to elucidate the difference of the clinical features, we analyzed the glycolipid composition of the heart, liver, and kidney obtained from the patient and from a hemizygote. Gas-liquid chromatography revealed that globotriaosylceramide (Gb3) was markedly increased in the heart (32.4 times higher than control) and increased to a lesser extent in the liver and kidney (3.74 and 6.79 times, respectively). The pattern of Gb3 accumulation in the heterozygote, where the highest increases were seen in the heart, was distinct from that in the hemizygote, where elevated levels of Gb3 and Ga2 were found in the kidney. Furthermore, the alpha-galactosidase activity in the heart, liver, and kidney of the heterozygote was 17%, 26%, and 36%, respectively, of normal controls, which correlated well with the accumulation of glycosphingolipid in the heart and with the disease's clinical manifestations. Two other hemizygotic patients, who were identified by low alpha-galactosidase activities, demonstrated the cardiac involvement.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K D MacDermot, A Holmes, and A H Miners Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females J. Med. Genet., November 1, 2001; 38(11): 769 - 775. [Full Text] [PDF]

				S.-C. Jung, I. P. Han, A. Limaye, R. Xu, M. P. Gelderman, P. Zerfas, K. Tirumalai, G. J. Murray, M. J. During, R. O. Brady, et al. Adeno-associated viral vector-mediated gene transfer results in long-term enzymatic and functional correction in multiple organs of Fabry mice PNAS, February 27, 2001; 98(5): 2676 - 2681. [Abstract] [Full Text] [PDF]

				R. Schiffmann, G. J. Murray, D. Treco, P. Daniel, M. Sellos-Moura, M. Myers, J. M. Quirk, G. C. Zirzow, M. Borowski, K. Loveday, et al. Infusion of alpha -galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease PNAS, January 4, 2000; 97(1): 365 - 370. [Abstract] [Full Text] [PDF]

				T. Ohshima, R. Schiffmann, G. J. Murray, J. Kopp, J. M. Quirk, S. Stahl, C.-C. Chan, P. Zerfas, J.-H. Tao-Cheng, J. M. Ward, et al. Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice PNAS, May 25, 1999; 96(11): 6423 - 6427. [Abstract] [Full Text] [PDF]