Abstract
Classical galactosemia is caused by the genetic deficiency of galactose-1-phosphate-urydyl-transferase resulting in clinical symptoms development during the first weeks of life including jaundice, hypotonia, lethargy, emesis, hepatomegaly, among others. Currently, dietary restriction of galactose is considered the standard for classical galactosemia management. For several years, severe dietary galactose restriction was considered necessary, implying restriction not only of dairy products, but also fruits, vegetables, legumes, and viscera. Such management failed to improve or prevent the appearance of long-term complications, by contrast, such restrictive approach may lead to nutritional deficiencies development. Thus, the last consensus suggests guidelines that are more flexible. In addition, the lack of knowledge regarding the physiopathology of the disease, and the toxicity threshold of the metabolites accumulated, make even more difficult to propose novel and more effective therapeutic approaches. This review summarizes the current state of knowledge regarding classical galactosemia in terms of physiopathology, long-term complications, newborn screening and genetic variants and their implications on galactosemia treatment, summed to the challenges that researchers working on this disease must address in future studies including the analysis of galactose content in foods, galactose tolerance threshold and search for novel therapeutic targets.
Highlights
Galactosemia is an inborn error of carbohydrate metabolism
This review summarizes the current state of knowledge regarding classical galactosemia in terms of physiopathology and its implications on galactosemia treatment, pointing out current challenges that should be addressed in order to improve our understanding of galactosemia pathological mechanisms and potentiate the development of novel therapeutic strategies
The development of a high number of studies using animal models, descriptive and intervention approaches, have allowed the formulation of diverse hypothesis around the pathophysiology of classical galactosemia which consider the accumulation of toxic metabolites as well as secondary defects on glycosylation
Summary
Galactosemia is an inborn error of carbohydrate metabolism. According to the enzyme altered in the Leloir pathway four different subtypes have been described [1,2]. Treatment does not prevent long-term complications such as premature ovarian failure, neurological manifestations, behavioral alterations, and decreased bone mineral density which have been reported to occur with different degrees of severity [2,11].
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