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The role of polyols in the pathophysiology of hypergalactosemia

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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.

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Abbreviations

GALT :

galactose-1-phosphate uridyltransferase

GALK :

galactokinase

AR :

aldose reductase

SDH :

sorbitol dehydrogenase

ARI :

aldose reductase inhibitor (s)

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  1. Division of Biochemical Development & Molecular Diseases, The Children's Hospital of Philadelphia, 34th Street & Civic Center Boulevard, 19104, Philadelphia, PA, USA

    Gerard T. Berry

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Berry, G.T. The role of polyols in the pathophysiology of hypergalactosemia. Eur J Pediatr 154 (Suppl 2), S53–S64 (1995). https://doi.org/10.1007/BF02143805

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