SNOMEDCT: 766982000; ORPHA: 86817; DO: 583;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9q34.11 | Hemolytic anemia due to adenylate kinase deficiency | 612631 | Autosomal recessive | 3 | AK1 | 103000 |
A number sign (#) is used with this entry because of evidence that hemolytic anemia due to adenylate kinase deficiency is caused by homozygous or compound heterozygous mutation in the AK1 gene (103000) on chromosome 9q34.
In 2 offspring of second-cousin Arab parents, Szeinberg et al. (1969) found marked AK deficiency with intermediate levels in the presumed heterozygotes. Severe anemia was present in both.
In the study of a black family, Beutler et al. (1982) found that despite barely detectable levels of adenylate kinase activity, probably representing guanylate kinase, red cells are able to maintain their adenine nucleotide levels and to circulate normally. They concluded that previously reported cases of AK deficiency represent a chance association of hemolysis with the enzyme deficiency, and not a cause-and-effect relationship.
In the family reported by Boivin et al. (1971), the proband had psychomotor retardation and moderate congenital hemolytic anemia with markedly diminished red cell AK activity. The parents had half-normal AK activity. Autosomal recessive inheritance was proposed.
Another family, Japanese, was reported by Miwa et al. (1983). The proband, a 10-year-old girl, had normal physical and mental development, mild to moderate hemolytic anemia from the neonatal period, and hepatosplenomegaly. Red cell AK activity was 44% of normal. Puzzlingly, the proband's mother, younger sister and maternal grandfather showed a half-normal enzyme activity.
Lachant et al. (1991) reported a fifth family with AK deficiency associated with hemolytic anemia. In none of the families had a cause-and-effect relationship to AK deficiency been established. Lachant et al. (1991) suggested that defects occur in multiple phosphotransferases in AK-deficient red blood cells and that these other defects produce deleterious lesions that promote the shortened red cell survival.
Toren et al. (1994) described a family in which 6 children showed AK deficiency; in 3 of them, G6PD deficiency was found in combination with AK deficiency. Although heterozygotes were asymptomatic, homozygotes had congenital chronic nonspherocytic hemolytic anemia with hemoglobin levels of 8-9 g/dl. Patients also deficient in G6PD suffered from a more severe hemolytic anemia with hemoglobin levels around 6 g/dl. The AK-deficient children were also mentally retarded. Splenectomy performed in 5 of the 6 children resulted in complete remission of the hemolytic process.
Bianchi et al. (1999) reported 2 sibs of Italian origin with mild chronic hemolytic anemia, psychomotor impairment, and undetectable adenylate kinase activity. They stated that all previously reported cases except that of Beutler et al. (1983) had chronic nonspherocytic hemolytic anemia. Psychomotor impairment occurred in only some patients.
In a patient with hemolytic anemia, Matsuura et al. (1989) demonstrated a mutation in exon 6 of the AK1 gene, which resulted in an arg128-to-trp substitution (103000.0001).
In an Italian child with hemolytic anemia and undetectable erythrocyte adenylate kinase activity, Qualtieri et al. (1997) identified homozygosity for a tyr164-to-cys substitution (103000.0003) in the AK1 gene.
In 2 sibs of Italian origin with mild chronic hemolytic anemia, psychomotor impairment, and undetectable adenylate kinase activity, Bianchi et al. (1999) identified an arg107-to-ter mutation (103000.0002) in the AK1 gene.
Beutler, E., Carson, D., Dannawi, H., Forman, L., Kuhl, W., West, C., Westwood, B. Metabolic compensation for profound erythrocyte adenylate kinase deficiency: a hereditary enzyme defect without hemolytic anemia. J. Clin. Invest. 72: 648-655, 1983. [PubMed: 6308059] [Full Text: https://doi.org/10.1172/JCI111014]
Beutler, E., Carson, D. A., Dannawi, H., Forman, L., Kuhl, W., West, C., Westwood, B. Red cell adenylate kinase deficiency: another non-disease? (Abstract) Blood 60: 33A only, 1982.
Bianchi, P., Zappa, M., Bredi, E., Vercellati, C., Pelissero, G., Barraco, F., Zanella, A. A case of complete adenylate kinase deficiency due to a nonsense mutation in AK-1 gene (arg107-to-stop, CGA-to-TGA) associated with chronic haemolytic anaemia. Brit. J. Haemat. 105: 75-79, 1999. [PubMed: 10233365]
Boivin, P., Galand, C., Hakim, J., Simony, D., Seligman, M. Deficit congenital en adenylate-kinase erythrocytaire. (Letter) Presse Med. 78: 1443 only, 1970. [PubMed: 5429371]
Boivin, P., Galand, C., Hakim, J., Simony, D., Seligman, M. Une nouvelle erythroenzymopathie: anemie hemolytique congenitale non spherocytaire et deficit hereditaire en adenylate-kinase erythrocytaire. Presse Med. 79: 215-218, 1971. [PubMed: 5546784]
Lachant, N. A., Zerez, C. R., Barredo, J., Lee, D. W., Savely, S. M., Tanaka, K. R. Hereditary erythrocyte adenylate kinase deficiency: a defect of multiple phosphotransferases? Blood 77: 2774-2784, 1991. [PubMed: 1646049]
Matsuura, S., Igarashi, M., Tanizawa, Y., Yamada, M., Kishi, F., Kajii, T., Fujii, H., Miwa, S., Sakurai, M., Nakazawa, A. Human adenylate kinase deficiency associated with hemolytic anemia: a single base substitution affecting solubility and catalytic activity of the cytosolic adenylate kinase. J. Biol. Chem. 264: 10148-10155, 1989. [PubMed: 2542324]
Miwa, S., Fujii, H., Tani, K., Takahashi, K., Takizawa, T., Igarashi, T. Red cell adenylate kinase deficiency associated with hereditary nonspherocytic hemolytic anemia: clinical and biochemical studies. Am. J. Hemat. 14: 325-333, 1983. [PubMed: 6305188] [Full Text: https://doi.org/10.1002/ajh.2830140403]
Qualtieri, A., Pedace, V., Bisconte, M. G., Bria, M., Gulino, B., Andreoli, V., Brancati, C. Severe erythrocyte adenylate kinase deficiency due to homozygous A-to-G substitution at codon 164 of human AK1 gene associated with chronic haemolytic anaemia. Brit. J. Haemat. 99: 770-776, 1997. [PubMed: 9432020] [Full Text: https://doi.org/10.1046/j.1365-2141.1997.4953299.x]
Singer, J. D., Brock, D. J. Half-normal adenylate kinase activity in three generations. Ann. Hum. Genet. 35: 109-114, 1971. [PubMed: 5571743] [Full Text: https://doi.org/10.1111/j.1469-1809.1956.tb01383.x]
Szeinberg, A., Gavendo, S., Cahane, D. Erythrocyte adenylate-kinase deficiency. (Letter) Lancet 293: 315-316, 1969. Note: Originally Volume I. [PubMed: 4179026] [Full Text: https://doi.org/10.1016/s0140-6736(69)91080-0]
Szeinberg, A., Kahana, D., Gavendo, S., Zaidman, J., Ben-Ezzer, J. Hereditary deficiency of adenylate kinase in red blood cells. Acta Haemat. 42: 111-126, 1969. [PubMed: 4982580] [Full Text: https://doi.org/10.1159/000208770]
Toren, A., Brok-Simoni, F., Ben-Bassat, I., Holtzman, F., Mandel, M., Neumann, Y., Ramot, B., Rechavi, G., Kende, G. Congenital haemolytic anaemia associated with adenylate kinase deficiency. Brit. J. Haemat. 87: 376-380, 1994. [PubMed: 7947281] [Full Text: https://doi.org/10.1111/j.1365-2141.1994.tb04925.x]