Sweet and sour: an update on classic galactosemia

Abstract

Classic galactosemia is a rare inherited disorder of galactose metabolism caused by deficient activity of galactose-1-phosphate uridylyltransferase (GALT), the second enzyme of the Leloir pathway. It presents in the newborn period as a life-threatening disease, whose clinical picture can be resolved by a galactose-restricted diet. The dietary treatment proves, however, insufficient in preventing severe long-term complications, such as cognitive, social and reproductive impairments. Classic galactosemia represents a heavy burden on patients’ and their families’ lives. After its first description in 1908 and despite intense research in the past century, the exact pathogenic mechanisms underlying galactosemia are still not fully understood. Recently, new important insights on molecular and cellular aspects of galactosemia have been gained, and should open new avenues for the development of novel therapeutic strategies. Moreover, an international galactosemia network has been established, which shall act as a platform for expertise and research in galactosemia. Herein are reviewed some of the latest developments in clinical practice and research findings on classic galactosemia, an enigmatic disorder with many unanswered questions warranting dedicated research.

Biochemical changes and clinical outcomes in 34 patients with classic galactosemia

“…2013;B e r r y2014), was unique to group 2 patients (Table 1). Global impairment of GALT activity would be expected to dysregulate many physiological pathways through various pathogenic mechanisms, including aberrant glycosylation and abnormal activation of signaling pathways (Lebea and Pretorius 2005;Liu et al 2012;Jumbo-Lucioni et al 2013;Coss et al 2014a, b;Balakrishnan et al 2016;Coelho et al 2017), although normal outcomes were still observed in several patients with severe genotypes in this study (Table 1,Fig.3).…”

“…Several mechanisms have been implicated in the pathogenesis of galactosemia. It has been suggested that the accumulation of toxic metabolites, galactose, galactitol, and GAL1P could cause permanent damage to various tissues and organs in the prenatal and the postnatal periods (Chen et al 1981;Bandyopadhyay et al 2003;Lai et al 2009;Coelho et al 2017). The impact of abnormal glycosylation on the physiological function of different glycoproteins and glycolipids has been considered a contributing factor to galactosemia complications (Liu et al 2012;C o s se ta l .2014a, b).…”

Including Classical Galactosaemia in the Expanded Newborn Screening Panel Using Tandem Mass Spectrometry for Galactose-1-Phosphate

“…However, due to the fact that they have reduced enzymatic activity there is a risk that they will show up as false positives. The allele frequency of the Duarte variant is reported to be 11% in the European population [16]. In the top 60 samples the frequency was 30%.…”

Electro‐kinetically driven route for highly sensitive blood pathology on a paper‐based device

“…Blood contains various simple sugars or monosaccharides like glucose, galactose, fructose, and mannose . Determination of fluctuations or variations in the concentration of plasma monosaccharide is one of the building blocks for assessing diseases like diabetes mellitus , galactosemia , obesity , and candidiasis .…”