TY - JOUR
T1 - Advances and Challenges in Classical Galactosemia. Pathophysiology and Treatment
AU - Caro N., Amanda R.
AU - Cornejo, Verónica
AU - Guevara-Morales, Johana M.
AU - Echeverri-Peña, Olga Y.
N1 - Publisher Copyright:
© 2022, Latin American Society Inborn Errors and Neonatal Screening. All rights reserved.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Classical Galactosemia
KW - Treatment
UR - http://www.scopus.com/inward/record.url?scp=85136195243&partnerID=8YFLogxK
U2 - 10.1590/2326-4594-JIEMS-2021-0026
DO - 10.1590/2326-4594-JIEMS-2021-0026
M3 - Review article
AN - SCOPUS:85136195243
SN - 2326-4098
VL - 10
JO - Journal of Inborn Errors of Metabolism and Screening
JF - Journal of Inborn Errors of Metabolism and Screening
M1 - e20210026
ER -