The Role of Polyols in the Pathophysiology of Hypergalactosemia

Overview

Journal Eur J Pediatr

Specialty Pediatrics

Date 1995 Jan 1

PMID 7671966

Citations 15

Authors

G T Berry

Affiliations

Soon will be listed here.

Abstract

Cellular accumulation of galactitol has been suggested to cause the apparent dietary-independent, long-term complications in classic galactosemia. Experimental animals rendered hypergalactosemic by galactose feeding accumulate tissue galactitol, as well as millimolar quantities of galactose, and manifest biochemical, physiological and pathological abnormalities which are generally eliminated or curtailed by the concomitant administration of an aldose reductase inhibitor. This includes reduced cellular content of the cyclic polyol, myo-inositol, which like galactitol may function as an alternate intracellular osmolyte. However, the abnormalities detected in experimental galactosemic animals are more compatible with findings in experimental diabetes mellitus than in human galactosemia. Because patients with galactokinase deficiency fail to manifest the CNS and ovarian complications which characterize classic galactosemia, yet during long-term lactose restriction excrete comparable urinary quantities of galactitol, this polyol alone is not likely to play an important role during postnatal life in the pathogenesis of long-term complications. Notwithstanding, a role for either galactitol or myo-inositol in an intrauterine toxicity cannot be dismissed.

Citing Articles

Harnessing the Power of Purple Sweet Potato Color and -Inositol to Treat Classic Galactosemia.

Hagen-Lillevik S, Johnson J, Siddiqi A, Persinger J, Hale G, Lai K Int J Mol Sci. 2022; 23(15).

PMID: 35955788 PMC: 9369367. DOI: 10.3390/ijms23158654.

Galactosemia: Biochemistry, Molecular Genetics, Newborn Screening, and Treatment.

Succoio M, Sacchettini R, Rossi A, Parenti G, Ruoppolo M Biomolecules. 2022; 12(7).

PMID: 35883524 PMC: 9313126. DOI: 10.3390/biom12070968.

Physiological and Pathological Roles of Aldose Reductase.

Singh M, Kapoor A, Bhatnagar A Metabolites. 2021; 11(10).

PMID: 34677370 PMC: 8541668. DOI: 10.3390/metabo11100655.

Novel mRNA-Based Therapy Reduces Toxic Galactose Metabolites and Overcomes Galactose Sensitivity in a Mouse Model of Classic Galactosemia.

Balakrishnan B, An D, Nguyen V, DeAntonis C, Martini P, Lai K Mol Ther. 2019; 28(1):304-312.

PMID: 31604675 PMC: 6952165. DOI: 10.1016/j.ymthe.2019.09.018.

Sweet and sour: an update on classic galactosemia.

Coelho A, Rubio-Gozalbo M, Vicente J, Rivera I J Inherit Metab Dis. 2017; 40(3):325-342.

PMID: 28281081 PMC: 5391384. DOI: 10.1007/s10545-017-0029-3.

References

Datiles M, Fukui H, Kuwabara T, KINOSHITA J . Galactose cataract prevention with sorbinil, an aldose reductase inhibitor: a light microscopic study. Invest Ophthalmol Vis Sci. 1982; 22(2):174-9. View

Frank R, Keirn R, Kennedy A, Frank K . Galactose-induced retinal capillary basement membrane thickening: prevention by Sorbinil. Invest Ophthalmol Vis Sci. 1983; 24(11):1519-24. View

Berry G, Palmieri M, Gross K, ACOSTA P, Henstenburg J, Mazur A . The effect of dietary fruits and vegetables on urinary galactitol excretion in galactose-1-phosphate uridyltransferase deficiency. J Inherit Metab Dis. 1993; 16(1):91-100. DOI: 10.1007/BF00711320. View

ENGERMAN R, Kern T . Aldose reductase inhibition fails to prevent retinopathy in diabetic and galactosemic dogs. Diabetes. 1993; 42(6):820-5. DOI: 10.2337/diab.42.6.820. View

Mizisin A, Powell H . Schwann cell injury is attenuated by aldose reductase inhibition in galactose intoxication. J Neuropathol Exp Neurol. 1993; 52(1):78-86. DOI: 10.1097/00005072-199301000-00010. View

Beigi B, OKeefe M, Bowell R, Naughten E, Badawi N, Lanigan B . Ophthalmic findings in classical galactosaemia--prospective study. Br J Ophthalmol. 1993; 77(3):162-4. PMC: 504462. DOI: 10.1136/bjo.77.3.162. View

ENGERMAN R, Kern T, Larson M . Nerve conduction and aldose reductase inhibition during 5 years of diabetes or galactosaemia in dogs. Diabetologia. 1994; 37(2):141-4. DOI: 10.1007/s001250050084. View

Maeda T, EISENBERG Jr F . Purification, structure, and catalytic properties of L-myo-inositol-1-phosphate synthase from rat testis. J Biol Chem. 1980; 255(18):8458-64. View

Mizisin A, Powell H, Myers R . Edema and increased endoneurial sodium in galactose neuropathy. Reversal with an aldose reductase inhibitor. J Neurol Sci. 1986; 74(1):35-43. DOI: 10.1016/0022-510x(86)90189-9. View

10.

Holub B . Metabolism and function of myo-inositol and inositol phospholipids. Annu Rev Nutr. 1986; 6:563-97. DOI: 10.1146/annurev.nu.06.070186.003023. View

11.

Stambolian D . Galactose and cataract. Surv Ophthalmol. 1988; 32(5):333-49. DOI: 10.1016/0039-6257(88)90095-1. View

12.

GABBAY K, KINOSHITA J . Mechanism of development and possible prevention of sugar cataracts. Isr J Med Sci. 1972; 8(8):1557-61. View

13.

Lou M, Dickerson Jr J, Chandler M, Brazzell R, York Jr B . The prevention of biochemical changes in lens, retina, and nerve of galactosemic dogs by the aldose reductase inhibitor AL01576. J Ocul Pharmacol. 1989; 5(3):233-40. DOI: 10.1089/jop.1989.5.233. View

14.

Das A, Frank R, Zhang N . Sorbinil does not prevent galactose-induced glomerular capillary basement membrane thickening in the rat. Diabetologia. 1990; 33(9):515-21. DOI: 10.1007/BF00404137. View

15.

Nishimura C, Lou M, KINOSHITA J . Depletion of myo-inositol and amino acids in galactosemic neuropathy. J Neurochem. 1987; 49(1):290-5. DOI: 10.1111/j.1471-4159.1987.tb03428.x. View

16.

Wong Y, Kalmbach S, Hartman B, Sherman W . Immunohistochemical staining and enzyme activity measurements show myo-inositol-1-phosphate synthase to be localized in the vasculature of brain. J Neurochem. 1987; 48(5):1434-42. DOI: 10.1111/j.1471-4159.1987.tb05682.x. View

17.

UNAKAR N, Tsui J . Inhibition of galactose-induced alterations in ocular lens with sorbinil. Exp Eye Res. 1983; 36(5):685-94. DOI: 10.1016/0014-4835(83)90106-9. View

18.

Vogel R, Gaifman M, Nitzan M . Increased intracranial pressure in galactosemia. Consider this diagnosis with a bulging fontanel, hepatomegaly, and failure to thrive. Clin Pediatr (Phila). 1976; 15(4):386-8. DOI: 10.1177/000992287601500414. View

19.

Okuda J, Yashima K, Inagaki K, Miwa I . Effects of an aldose reductase inhibitor, 1-[(p-bromophenyl)-sulfonyl]hydantoin, on cataract formation and tissue polyol levels in galactosemic rats. Chem Pharm Bull (Tokyo). 1985; 33(7):2990-5. DOI: 10.1248/cpb.33.2990. View

20.

Wang K, Bohren K, GABBAY K . Characterization of the human aldose reductase gene promoter. J Biol Chem. 1993; 268(21):16052-8. View