Alternative titles; symbols
SNOMEDCT: 124302001; ICD10CM: E74.29; ORPHA: 352, 79237; DO: 14695;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q25.1 | Galactokinase deficiency with cataracts | 230200 | Autosomal recessive | 3 | GALK1 | 604313 |
A number sign (#) is used with this entry because galactosemia II (GALAC2), or galactokinase deficiency, is caused by homozygous or compound heterozygous mutation in the GALK1 gene (604313) on chromosome 17q24.
Galactosemia II (GALAC2), or galactokinase deficiency, is an autosomal recessive disorder that causes cataract formation in children not maintained on a lactose-free diet. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens (Asada et al., 1999).
For a discussion of genetic heterogeneity of galactosemia, see GALAC1 (230400).
Gitzelmann (1967) reported juvenile cataracts related to galactokinase deficiency in 2 sibs of a consanguineous Gypsy family; Fanconi had previously reported the cases as instances of 'galactose diabetes;' however, GALT activity in red cells was normal. There was no mental retardation. Several close relatives had reduced red cell galactokinase activity, suggesting that they were heterozygotes.
Cook et al. (1971) described an affected newborn, ascertained because of hyperbilirubinemia, who had resolution of the cataracts with dietary management. Segal et al. (1979), who studied affected brothers, suggested that mental retardation may occur with galactokinase deficiency.
Prachal et al. (1978) associated presenile cataracts with heterozygosity for galactokinase deficiency and galactose-uridyl transferase deficiency.
Bosch et al. (2002) reviewed the clinical features of galactokinase deficiency in describing 55 patients in 25 publications. Cataract was reported in most patients. Clinical abnormalities other than cataract were reported in 15 (35%) of 43 cases for which information was available. However, all symptoms were reported infrequently and a causal relationship with the galactokinase deficiency could not be determined. Pseudotumor cerebri is a rare but consistently reported abnormality in this disorder.
In 2 patients with galactokinase deficiency and cataracts, Stambolian et al. (1995) identified 2 different homozygous mutations in the GALK1 gene (604313.0001; 604313.0002). One of the patients had been reported by Pickering and Howell (1972).
In affected members of 6 Romani (Gypsy) families from Bulgaria with galactokinase deficiency, Kalaydjieva et al. (1999) identified a homozygous mutation in the GALK1 gene (P28T; 604313.0003). The authors concluded that this mutation was most likely responsible for the galactokinase deficiency in the cases originally described by Gitzelmann (1967).
Asada et al. (1999) identified 5 mutations in the GALK1 gene in 7 unrelated Japanese patients with galactokinase deficiency.
Mayes and Guthrie (1968) found 6 heterozygotes for galactokinase deficiency among 642 persons in Buffalo, N.Y.
In Italy, Magnani et al. (1982) estimated the heterozygote frequency to be 1 in 310; 2 persons presumably heterozygous by biochemical criteria were detected among 620 persons studied.
Asada, M., Okano, Y., Imamura, T., Suyama, I., Hase, Y., Isshiki, G. Molecular characterization of galactokinase deficiency in Japanese patients. J. Hum. Genet. 44: 377-382, 1999. [PubMed: 10570908] [Full Text: https://doi.org/10.1007/s100380050182]
Beutler, E., Matsumoto, F., Kuhl, W., Krill, A. E., Levy, N., Sparkes, R., Degnan, M. Galactokinase deficiency as a cause of cataracts. New Eng. J. Med. 288: 1203-1206, 1973. [PubMed: 4700553] [Full Text: https://doi.org/10.1056/NEJM197306072882303]
Bosch, A. M., Bakker, H. D., van Gennip, A. H., van Kempen, J. V., Wanders, R. J. A., Wijburg, F. A. Clinical features of galactokinase deficiency: a review of the literature. J. Inherit. Metab. Dis. 25: 629-634, 2002. [PubMed: 12705493] [Full Text: https://doi.org/10.1023/a:1022875629436]
Cook, J. G. H., Don, N. A., Mann, T. P. Hereditary galactokinase deficiency. Arch. Dis. Child. 46: 465-469, 1971. [PubMed: 5109408] [Full Text: https://doi.org/10.1136/adc.46.248.465]
Gitzelmann, R. Hereditary galactokinase deficiency, a newly recognized cause of juvenile cataracts. Pediat. Res. 1: 14-23, 1967.
Kalaydjieva, L., Perez-Lezaun, A., Angelicheva, D., Onengut, S., Dye, D., Bosshard, N. U., Jordanova, A., Savov, A., Yanakiev, P., Kremensky, I., Radeva, B., Hallmayer, J., Markov, A., Nedkova, V., Tournev, I., Aneva, L., Gitzelmann, R. A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). Am. J. Hum. Genet. 65: 1299-1307, 1999. [PubMed: 10521295] [Full Text: https://doi.org/10.1086/302611]
Kaloud, H., Sitzmann, F. C. The galactokinase deficiency in two human populations: Styria (Austria) and Franconia (Bavaria): a comparative investigation on gene frequency. Z. Kinderheilk. 116: 185-192, 1974. [PubMed: 4360413]
Kerr, M. M., Logan, R. W., Cant, J. S., Hutchison, J. H. Galactokinase deficiency in a newborn infant. Arch. Dis. Child. 46: 864-866, 1971. [PubMed: 5129188] [Full Text: https://doi.org/10.1136/adc.46.250.864]
Levy, N. S., Krill, A. E., Beutler, E. Galactokinase deficiency and cataracts. Am. J. Ophthal. 74: 41-48, 1972. [PubMed: 5036447] [Full Text: https://doi.org/10.1016/0002-9394(72)91123-3]
Litman, N., Kanter, A. I., Finberg, L. Galactokinase deficiency presenting as pseudotumor cerebri. J. Pediat. 86: 410-411, 1975. [PubMed: 163306] [Full Text: https://doi.org/10.1016/s0022-3476(75)80973-5]
Magnani, M., Cucchiarini, L., Stocchi, V., Stocchi, O., Carnevali, G., Dacha, M., Fornaini, G. Human erythrocyte galactokinase: a population survey. Hum. Hered. 32: 274-279, 1982. [PubMed: 7129459] [Full Text: https://doi.org/10.1159/000153306]
Mayes, J. S., Guthrie, R. Detection of heterozygotes for galactokinase deficiency in a human population. Biochem. Genet. 2: 219-230, 1968. [PubMed: 5715186] [Full Text: https://doi.org/10.1007/BF01474761]
Oberman, A. E., Wilson, W. A., Fraiser, S. D., Donnell, G. N., Bergren, W. R. Galactokinase-deficiency cataracts in identical twins. Am. J. Ophthal. 74: 887-892, 1972. [PubMed: 4644736] [Full Text: https://doi.org/10.1016/0002-9394(72)91209-3]
Pickering, W. R., Howell, R. R. Galactokinase deficiency: clinical and biochemical findings in a new kindred. J. Pediat. 81: 50-55, 1972. [PubMed: 5034870] [Full Text: https://doi.org/10.1016/s0022-3476(72)80373-1]
Prachal, J. T., Conrad, M. E., Skalka, H. W. Association of presenile cataracts with heterozygosity for galactosaemic states and with riboflavin deficiency. Lancet 311: 12-13, 1978. Note: Originally Volume I. [PubMed: 74495] [Full Text: https://doi.org/10.1016/s0140-6736(78)90359-8]
Segal, S., Rutman, J. Y., Frimpter, G. W. Galactokinase deficiency and mental retardation. J. Pediat. 95: 750-752, 1979. [PubMed: 490246] [Full Text: https://doi.org/10.1016/s0022-3476(79)80729-5]
Stambolian, D., Ai, Y., Sidjanin, D., Nesburn, K., Sathe, G., Rosenberg, M., Bergsma, D. J. Cloning of the galactokinase cDNA and identification of mutations in two families with cataracts. Nature Genet. 10: 307-312, 1995. [PubMed: 7670469] [Full Text: https://doi.org/10.1038/ng0795-307]
Thalhammer, O., Gitzelmann, R., Pantlitschko, M. Hypergalactosemia and galactosuria due to galactokinase deficiency in a newborn. Pediatrics 42: 441-445, 1968. [PubMed: 5695665]