Alternative titles; symbols
DO: 0111046;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 7q21.11 | Platelet glycoprotein IV deficiency | 608404 | Autosomal recessive | 3 | CD36 | 173510 |
A number sign (#) is used with this entry because platelet glycoprotein IV (CD36) deficiency is caused by homozygous or compound heterozygous mutation in the CD36 antigen gene (173510) on chromosome 7q21.
CD36 deficiency can be divided into 2 subgroups (Yamamoto et al., 1994). The type I phenotype is characterized by platelets and monocytes/macrophages exhibiting CD36 deficiency; indeed, probably no cells express CD36. The type II phenotype lacks the surface expression of CD36 in platelets, but expression in monocytes/macrophages is near normal.
Yufu et al. (1990) found decreased glycosylation of platelet membrane glycoprotein IV in a 45-year-old male who had been found to have macrothrombocytopenia on routine blood examination. He had no history of hemorrhagic diathesis. Four members of his family, including a son, also had macrothrombocytopenia without notable bleeding tendency. The Bernard-Soulier syndrome (231200) is another form of familial macrothrombocytopenia, which is caused by a defect in platelet glycoprotein Ib (138720).
In a thrombocytopenic patient with refractoriness to HLA-matched platelet transfusion, Ikeda et al. (1989) demonstrated a new platelet-specific antigen, Nak(a); Tomiyama et al. (1990) demonstrated that the corresponding antibody reacts with GP IV. Yamamoto et al. (1990) demonstrated that Nak(a)-negative platelets lacked detectable GP IV. The authors observed that these individuals with deficiency of platelet GP IV are apparently healthy and suffer no obvious hemostatic problems, but they are at risk for developing isoantibodies after infusion of Nak(a)-positive platelets.
Tanaka et al. (1997) stated that up to 40% of Japanese patients with hereditary hypertrophic cardiomyopathy (192600) have CD36 deficiency. They also noted that others have reported an increased frequency of CD36 deficiency in Japanese patients with coronary heart disease, as well as the occurrence of type II diabetes with either insulin resistance or hypertriglyceridemia, hypertension, and coronary heart disease in patients with CD36 deficiency.
Yanai et al. (2000) found that 44 Japanese individuals with type II CD36 deficiency had significantly increased serum LDL cholesterol compared to 731 controls. Similar findings were observed for 4 individuals with type I CD36 deficiency, but the differences were not statistically significant because of small sample size.
Miyaoka et al. (2001) examined 26 Japanese patients with CD36 deficiency and found increased levels of plasma triglycerides, fasting plasma glucose, and high blood pressure. Five patients who underwent glucose clamp studies were all found to have systemic insulin resistance. Miyaoka et al. (2001) concluded that CD36 deficiency might be a cause of human insulin resistance syndrome in the Japanese population.
Yanai et al. (2007) evaluated the aerobic exercise capacity of 12 women with CD36 deficiency, including 2 with type I and 10 with type II. Whereas normal controls showed a decrease in serum fatty acid levels during exercise, fatty acid levels in patients with CD36 deficiency did not change, indicating decreased fatty acid uptake and utilization. Patients also showed significantly lower ventilatory threshold compared to controls. The findings indicated that CD36-mediated fatty acid oxidation is an important determinant for aerobic exercise capacity in humans.
CD36 deficiency is present in 2 to 3% of Japanese, Thais, and Africans, but in less than 0.3% of Americans of European descent (Ikeda et al., 1989; Yamamoto et al., 1990; Kashiwagi et al., 1995; Urwijitaroon et al., 1995; Curtis and Aster, 1996).
Lee et al. (1999) found that CD36 deficiency is frequent in sub-Saharan Africans, as it is in Asians, and that development of anti-CD36 can lead to serious complications in multiply transfused patients, such as those with sickle cell disease.
Aitman et al. (2000) found that African populations contain an exceptionally high frequency of mutations in the CD36 gene. Unexpectedly, these mutations that cause CD36 deficiency (173510.0002-173510.0003) are associated with susceptibility to severe cerebral malaria (611162), suggesting that the presence of distinct CD36 mutations in Africans and Asians is due to some selection pressure other than malaria.
In a study of 790 Japanese individuals, Yanai et al. (2000) determined that the frequency of type I and type II CD36 deficiency in Japanese was 0.5 and 5.7%, respectively.
Kashiwagi et al. (2001) stated that the incidence of type I and type II CD36-deficient subjects in Japanese is 0.3% and 4.0%, respectively. Type I subjects may produce isoantibodies against CD36 during pregnancy or transfusion, leading to neonatal immune thrombocytopenia, refractoriness to HLA-matched platelet transfusion, or posttransfusion purpura.
In platelets from 4 of 5 Japanese patients with type II platelet glycoprotein IV deficiency, Kashiwagi et al. (1993) identified a mutation in the CD36 gene (P90S; 173510.0001). In 2 patients with type I CD36 deficiency, Kashiwagi et al. (1995) identified the P90S mutation in both platelets and monocytes. Among 28 Japanese patients with type I CD36 deficiency, Kashiwagi et al. (2001) found that the P90S mutation had a greater than 50% frequency. None of the 4 subjects who possessed isoantibodies against CD36 had the P90S mutation, suggesting that this mutation prevents the production of isoantibodies against CD36.
Aitman, T. J., Cooper, L. D., Norsworthy, P. J., Wahid, F. N., Gray, J. K., Curtis, B. R., McKeigue, P. M., Kwiatkowski, D., Greenwood, B. M., Snow, R. W., Hill, A. V., Scott, J. Malaria susceptibility and CD36 mutation. Nature 405: 1015-1016, 2000. [PubMed: 10890433] [Full Text: https://doi.org/10.1038/35016636]
Curtis, B. R., Aster, R. H. Incidence of the Nak(a)-negative platelet phenotype in African Americans is similar to that of Asians. Transfusion 36: 331-334, 1996. [PubMed: 8623134] [Full Text: https://doi.org/10.1046/j.1537-2995.1996.36496226147.x]
Ikeda, H., Mitani, T., Ohnuma, M., Haga, H., Ohtzuka, S., Kato, T., Nakase, T., Sekiguchi, S. A new platelet-specific antigen, Nak(a), involved in the refractoriness of HLA-matched platelet transfusion. Vox Sang. 57: 213-217, 1989. [PubMed: 2617957] [Full Text: https://doi.org/10.1111/j.1423-0410.1989.tb00826.x]
Kashiwagi, H., Honda, S., Tomiyama, Y., Mizutani, H., Take, H., Honda, Y., Kosugi, S., Kanayama, Y., Kurata, Y., Matsuzawa, Y. A novel polymorphism in glycoprotein IV (replacement of proline-90 by serine) predominates in subjects with platelet GPIV deficiency. Thromb. Haemost. 69: 481-484, 1993. [PubMed: 7686693]
Kashiwagi, H., Tomiyama, Y., Honda, S., Kosugi, S., Shiraga, M., Nagao, N., Sekiguchi, S., Kanayama, Y., Kurata, Y., Matsuzawa, Y. Molecular basis of CD36 deficiency: evidence that a 478-C-to-T substitution (proline90-to-serine) in CD36 cDNA accounts for CD36 deficiency. J. Clin. Invest. 95: 1040-1046, 1995. [PubMed: 7533783] [Full Text: https://doi.org/10.1172/JCI117749]
Kashiwagi, H., Tomiyama, Y., Nozaki, S., Kiyoi, T., Tadokoro, S., Matsumoto, K., Honda, S., Kosugi, S., Kurata, Y., Matsuzawa, Y. Analyses of genetic abnormalities in type I CD36 deficiency in Japan: identification and cell biological characterization of two novel mutations that cause CD36 deficiency in man. Hum. Genet. 108: 459-466, 2001. [PubMed: 11499670] [Full Text: https://doi.org/10.1007/s004390100525]
Lee, K., Godeau, B., Fromont, P., Plonquet, A., Debili, N., Bachir, D., Reviron, D., Gourin, J., Fernandez, E., Galacteros, F., Bierling, P. CD36 deficiency is frequent and can cause platelet immunization in Africans. Transfusion 39: 873-879, 1999. [PubMed: 10504124] [Full Text: https://doi.org/10.1046/j.1537-2995.1999.39080873.x]
Miyaoka, K., Kuwasako, T., Hirano, K., Nozaki, S., Yamashita, S., Matsuzawa, Y. CD36 deficiency associated with insulin resistance. (Letter) Lancet 357: 686-687, 2001. [PubMed: 11247555] [Full Text: https://doi.org/10.1016/s0140-6736(00)04138-6]
Tanaka, T., Sohmiya, K., Kawamura, K. Is CD36 deficiency an etiology of hereditary hypertrophic cardiomyopathy? J. Molec. Cell. Cardiol. 29: 121-127, 1997. [PubMed: 9040027] [Full Text: https://doi.org/10.1006/jmcc.1996.0257]
Tomiyama, Y., Take, H., Ikeda, H., Mitani, T., Furubayashi, T., Mizutani, H., Yamamoto, N., Tandon, N. N., Sekiguchi, S., Jamieson, G. A., Kurata, Y., Yonezawa, T., Tarui, S. Identification of the platelet-specific alloantigen, Nak(a), on platelet membrane glycoprotein IV. Blood 75: 684-687, 1990. [PubMed: 2297570]
Urwijitaroon, Y., Barusrux, S., Romphruk, A., Puapairoj, C. Frequency of human platelet antigens among blood donors in northeastern Thailand. Transfusion 35: 868-870, 1995. [PubMed: 7570919] [Full Text: https://doi.org/10.1046/j.1537-2995.1995.351096026370.x]
Yamamoto, N., Akamatsu, N., Sakuraba, H., Yamazaki, H., Tanoue, K. Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type I) or the presence (type II) of glycoprotein IV on monocytes. Blood 83: 392-397, 1994. [PubMed: 7506948]
Yamamoto, N., Ikeda, H., Tandon, N. N., Herman, J., Tomiyama, Y., Mitani, T., Sekiguchi, S., Lipsky, R., Kralisz, U., Jamieson, G. A. A platelet membrane glycoprotein (GP) deficiency in healthy blood donors: Nak(a-) platelets lack detectable GPIV (CD36). Blood 76: 1698-1703, 1990. [PubMed: 1699620]
Yanai, H., Chiba, H., Morimoto, M., Abe, K., Fujiwara, H., Fuda, H., Hui, S.-P., Takahashi, Y., Akita, H., Jamieson, G. A., Kobayashi, K., Matsuno, K. Human CD36 deficiency is associated with elevation in low-density lipoprotein-cholesterol. Am. J. Med. Genet. 93: 299-304, 2000. [PubMed: 10946357] [Full Text: https://doi.org/10.1002/1096-8628(20000814)93:4<299::aid-ajmg9>3.0.co;2-7]
Yanai, H., Watanabe, I., Ishii, K., Morimoto, M., Fujiwara, H., Yoshida, S., Hui, S.-P., Matsuno, K., Chiba, H. Attenuated aerobic exercise capacity in CD36 deficiency. J. Med. Genet. 44: 445-447, 2007. [PubMed: 17412877] [Full Text: https://doi.org/10.1136/jmg.2007.050070]
Yufu, Y., Ideguchi, H., Narishige, T., Suematsu, E., Toyoda, K., Nishimura, J., Nawata, H., Oda, S. Familial macrothrombocytopenia associated with decreased glycosylation of platelet membrane glycoprotein IV. Am. J. Hemat. 33: 271-273, 1990. [PubMed: 2316511] [Full Text: https://doi.org/10.1002/ajh.2830330411]