Deficiency in glucose-6-phosphate dehydrogenase (G6PD) is the most common enzymopathy, and more than 125 different mutations causing G6PD deficiency have been identified. Chronic haemolytic anaemia (CHA) associated with G6PD deficiency is rare, but there is a cluster of mutations causing CHA between amino acids 361–428 which are encoded by exon 10 of the G6PD gene. This region is involved in the dimer formation of the active G6PD enzyme and therefore plays an important role for enzyme stability and activity. Here, we report a 17-year-old patient with CHA, who carries a rare G → A mutation at nucleotide 1160 which causes an R387H amino acid substitution. We review the reports of the seven previously described patients with this mutation, concluding that G6PD deficiency should be considered as a rare differential diagnosis of chronic haemolytic, non-spherocytic anaemia.

Vulliamy T, Beutler E, Luzzatto L: Variants of glucose-6-phosphate dehydrogenase are due to missense mutations spread throughout the coding region of the gene. Hum Mutat 1993;2:159–167.
Ruwende C, Khoo SC, Snow RW, Yates SNR, Kwiatkowski D, Gupta A, Warn P, Allsopp CEM, Gilbert SC, Peschu N, Newbold CI, Greenwood BM, Marsh K, Hill AVS: Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 1995;376:246–249.
WHO working group: Glucose-6-phosphate dehydrogenase deficiency. Bull World Health Organ 1989;67:601.
Thein SL, Hinton J: A simple and rapid method of direct sequencing using Dynabeads. Br J Haematol 1991;79:113–115.
Hirono A, Kuhl W, Gelbart T, Forman L, Fairbanks VF, Beutler E: Identification of the binding domain for NADP+ of human glucose-6-phosphate dehydrogenase by sequence analysis of mutants. Proc Natl Acad Sci USA 1989;86:10015–10017.
Pai GS, Sprenkle JA, Do TT, Mareni CE, Migeon BR: Localization of loci for hypoxanthine phosphoribosyltransferase and glucose-6-phosphate dehydrogenase and biochemical evidence of nonrandom X chromosome expression from studies of a human X-autosome translocation. Proc Natl Acad Sci USA 1980;77:2810–2813.
Persico MG, Viglietto G, Martini G, Toniolo D, Paonessa G, Moscatelli C, Dono R, Vulliamy T, Luzzatto L, D’Urso M: Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: Primary structure of the protein and unusual 5′ non-coding region. Nucleic Acids Res 1986;14:2511–2522.
Martini G, Toniolo D, Vulliamy T, Luzzatto L, Dono R, Viglietto G, Paonessa G, D’Urso M, Persico MG: Structural analysis of the X-linked gene encoding human glucose 6-phosphate dehydrogenase. EMBO J 1986;5:1849–1855.
Adam A: Linkage between deficiency of glucose-6-phosphate dehydrogenase and colour-blindness. Nature 1961;189:686.
Davies KE, Mandel JL, Monaco AP, Nussbaum RL, Willard HF: Report of the committee on the genetic constitution of the X chromosome. Cytogenet Cell Genet 1990;55:254–313.
Xu W, Westwood B, Bartsocas CS, Malcorra-Azpiazu JJ, Indrak K, Beutler E: Glucose-6-phosphate dehydrogenase mutations and haplotypes in various ethnic groups. Blood 1995;85:257–263.
Hirono A, Fujii H, Shima M, Miwa S: G6PD Nara: A new class 1 glucose-6-phosphate dehydrogenase variant with an eight amino acid deletion. Blood 1993;82:3250–3252.
Kanno H, Takano T, Fujii H, Tani K, Morisaki T, Hirono A, Kumakawa T, Ogura H, Takahashi K, Tsutsumi H, et al: A new glucose-6-phosphate dehydrogenase variant (G6PD Iwate) associated with congenital non-spherocytic hemolytic anemia. Nippon Ketsueki Gakkai Zasshi 1988;51:715–719.
Chiba Y, Takizawa S, Kishi K, Hattori A, Shibata A, Matsumoto N, Fujii J, Miwa S: A new glucose 6-phosphate dehydrogenase (G6PD) variant (G6PD Niigata) with chronic hemolysis and liver hemochromatosis. Nippon Naika Gakkai Zasshi, 1989;78:41–47.
Miwa S, Fujii H, Nakatsuji T, Ishida Y, Oda E, Kaneto A, Motokawa M, Ariga Y, Fukuchi S, Sasai S, Hiraoka K, Kashii H, Kodama T: Four new electrophoretically slow-moving glucose 6-phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: Gd(–) Kurume, Gd(–) Fukushima, Gd(–) Yamaguchi and Gd(–) Wakayama. Am J Haematol 1978;5:131–138.
Gaetani GF, Galiano S, Melani C, Miglino M, Forni GL, Napoli G, Perrone L, Ferraris AM: A new glucose-6-phosphate dehydrogenase variant with congenital nonspherocytic hemolytic anemia (G6PD Genova). Biochemical characterization and mosaicism expression in the heterozygote. Hum Genet 1990;84:337–340.
Snyder LM, Necheles TF, Reddy WJ: G-6-PD Worcester. A new variant, associated with X-linked optic atrophy. Am J Med 1970;49:125–132.
Vulliamy TJ, Kaeda JS, Ait-Chafa D, Mangerini R, Roper D, Barbot J, Mehta AB, Athanassiou-Metaxa M, Luzzatto L, Mason PJ: Clinical and haematological consequences of reccurent G6PD mutations and a single new mutation causing chronic nonspherocytic haemolytic anaemia. Br J Haematol 1998;101:670–675.
Jablonska-Skwiecinska E, Lewandowska I, Plochocka D, Topczewski J, Zimowski JG, Klopocka J, Burzynska B: Several mutations including two novel mutations of the glucose-6-phosphate dehydrogenase gene in Polish G6PD deficient subjects with chronic nonspherocytic hemolytic anemia, acute hemolytic anemia, and favism. Human Mutat 1999;14:477–484.
Beutler E: Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med 1991;324:169–174.
Au SWN, Gover S, Lam VMS, Adams MJ: Human glucose-6-phosphate dehydrogenase: The crystal structure reveals a structural NADP+ molecule and provides insights into enzyme deficiency. Structure 2000;8:293–303.
Naylor CE, Rowland P, Basak AK, Gover S, Mason PJ, Bautista JM, Vulliamy TJ, Luzzatto L, Adams MJ: Glucose 6-phosphate dehydrogenase mutations causing enzyme deficiency in a model of the tertiary structure of the human enzyme. Blood 1996;87:2974–2982.
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