Abstract
Summary: Galactokinase deficiency (McKusick 230200) is a rare autosomal recessive inborn error of galactose metabolism. Cataract and, rarely, pseudotumor cerebri caused by galactitol accumulation seem to be the only consistently reported abnormalities in this disorder. We performed a literature search to obtain information on the clinical spectrum of galactokinase deficiency. A total of 25 publications were traced describing 55 galactokinase-deficient patients. Cataract was reported in most patients. Clinical abnormalities other than cataract were reported in 15 (35%) out of 43 cases on which information was available. However, all symptoms were reported infrequently and a causal relationship with the galactokinase deficiency is unlikely. As cataract and pseudotumor cerebri appear to be the sole complications of galactokinase deficiency, the outcome for patients with galactokinase deficiency is much better than for patients with classical galactosaemia (McKusick 230400), a more common autosomal recessive disorder of galactose metabolism caused by galactose-1-phosphate uridyltransferase (GALT; EC 2.7.7.12) deficiency. Long-term follow-up of patients with this disorder has shown that, in spite of a severely galactose-restricted diet, most patients develop abnormalities such as a disturbed mental and/or motor development, dyspraxia and hypergonadotropic hypogonadism. Endogenous production of galactose has been considered an important aetiological factor. Although damage may well occur inutero, available evidence suggests that damage will continue after birth. Inhibition of galactokinase may then be a promising approach for controlling damage in GALT-deficient patients.
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REFERENCES
Ai Y, Zheng Z, O'Brien-Jenkins A, et al (2000) A mouse model of galactose-induced cataracts. Hum Mol Genet 9(12): 1821–1827.
Beutler E, Matsumono F, Kuhl W, et al (1973) Galactokinase deficiency as a cause of cataracts. N Engl J Med 288: 1203.
Borzy MS, Wolff L, Gewurz A, Buist N, Lovrien E (1984) Recurrent sepsis with deficiencies of C2 and galactokinase. Am J Dis Child 138: 186–191.
Colin J, Voyer M, Thomas D, Schapira F, Satge P (1976) Cataracte par deficit en galactokinase chez un premature. Arch Fr Pediatr 33: 77–82.
Cook JGH, Don NA, Mann TP (1971) Hereditary galactokinase deficiency. Arch Dis Child 46: 465–469.
Dahlqvist A, Gamsport I, Madsen H (1970) A patient with hereditary galactokinase deficiency. Acta Paediatr Scand 59: 669–675.
Gitzelmann R (1965) Deficiency of erythrocyte galactokinase in a patient with galactose diabetes. Lancet 2: 670.
Gitzelmann R (1967) Hereditary galactokinase deficiency, a newly recognized cause of juvenile cataracts. Pediatr Res 1: 14.
Gitzelmann R, Wells HJ, Segal S (1974) Galactose metabolism in a patient with hereditary galactokinase deficiency. Eur J Clin Invest 4: 79–84.
Holton JB, Walter JH, Tyfield LA (2001) Galactosemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill: New York, 1553–1583.
Hunter M, Angelicheva D, Levy HL, Pueschel SM, Kalaydjieva L (2001) Novel mutations in the GALKI gene in patients with galactokinase deficiency. Hum Mutat 17: 77–78.
Huttenlocher PR, Hillman RE, Hsia YE (1970) Pseudotumor cerebri in galactosemia. J Pediatr 76: 902.
Kalaydjieva L, Perez-Lezaun A, Angelicheva D, et al (1999) A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). Am J Hum Genet 65: 1299–1307.
Kaloud H, Sitzmann FC, Mayer R, Paltauf F (1972) Klinische und Biochemische Befunde bei einem Kleinkind mit hereditarem Galactokinase-Defect. Klin Padiatr 185: 18–22.
Kerr MM, Logan W, Cant JS, et al (1971) Galactokinase deficiency in a newborn infant. Arch Dis Child 46: 864–866.
Kolosha V, Anoia E, De Cespedes C, et al (2000) Novel mutations in 13 probands with galactokinase deficiency. Hum Mutat 15: 447–453.
Kurt I, Serdar M, Mutlu F, Bayer A, Allen JT, Kutlay T (2002) Galactokinase deficiency: a case report. J Pediatr Ophthalmol Strabismus 39(1): 41–43.
Levy HL (1980) Screening for galactosemia. In: Burman D, Holton JB, Pennocl CA, eds. Inherited Disorders of Carbohydrate Metabolism. Lancaster: MTP, 133–139.
Levy NS, Krill AE, Beutler E (1972) Galactokinase deficiency and cataracts. Am J Ophthalmol 74(1): 41–48.
Linneweh F, Schaumloffel E, Vetrella M (1970) Galactokinase-defect bei einem neugeborenen. Klin Wochenschr 48(1): 31–33.
Litman N, Kanter A, Finberg L (1975) Galactokinase deficiency presenting as pseudotumor cerebri J Pediatr 86(3): 410–412.
Mayes JS, Guthrie R (1968) Detection of heterozygoyes for galactokinase deficiency in a human population Biochem Genet 2: 219–230.
Monteleone JA, Beutler E, Monteleone PL, Utz CL, Casey EC (1971) Cataracts, galactosuria and hypergalactosemia due to galactokinase deficiency in a child. Am J Med 50: 403–407.
Ning C, Reynolds R, Chen J, et al (2000) Galactose metabolism by the mouse with galactose-1–phosphate uridyltransferase deficiency. Pediatr Res 48(2): 211–217.
Olambiwonnu NO, MC Vie R, Ng WG, Frasier SD, Donnell GN (1974) Galactokinase deficiency in twins: clinical and biochemical studies Pediatrics 53(3): 314–317.
Pickering WR, Howel RR (1972) Galactokinase deficiency: clinical and biochemical findings in a new kindred. J Pediatr 81(1): 50–55.
Segal S, Rutman JY, Frimpter GW (1979) Galactokinase deficiency and mental retardation. J Pediatr 95(5): 750–752.
Sitzmann FC, Schmid RD, Kaloud H (1977) Excretion of galactitol in the urine of heterozygotes of both forms of galactosemia. Clin Chim Acta 75: 313–319.
Stambolian D, Ai Y, Sidjanin D, et al (1995) Cloning of the galactokinase gene and identification of mutations in two families with cataract. Nature Genetics 10: 307–312.
Thalhammer O, Gitzelmann R, Pantlitschko M (1968) Hypergalactosemia and galactosuria due to galactokinase deficiency in a newborn. Pediatrics 42(3): 441–445.
Vecchio F, Carnevale F, Di Bitonto G (1976) Galactokinase deficiency in an Italian infant. In: Bickel H, Stern J, eds. Inborn Errors of Calcium and Bone Metabolism. Baltimore: University Park Press, 317–324.
Vigneron C, Marchel C, Deifts C, Vidailhet M, Pierson M, Neimann M (1970) Deficit partiel et transitoire en galactokinase erythrocytaire chez un nouvea u-ne. Arch Fr Pediatr 27: 523–531.
Wang ZI, Berry GT, Dreha ZF, Zhao H, Segal S, Zimmerman RA (2001) Proton magnetic resonance spectroscopy of brain metabolites in galactosemia. Ann Neurol 50(2): 266–269.
Xu YK, Ng WG, Kaufman FR, Donnell GN (1989) Uridine nucleotide sugars in erythrocytes of patients with galactokinase deficiency. J Inherit Metab Dis 12: 445–450.
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Bosch, A.M., Bakker, H.D., van Gennip, A.H. et al. Clinical features of galactokinase deficiency:A review of the literature. J Inherit Metab Dis 25, 629–634 (2003). https://doi.org/10.1023/A:1022875629436
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DOI: https://doi.org/10.1023/A:1022875629436