Table 2.
Summary of the proposed pathophysiological mechanisms in systematically reviewed studies
| Type of galactosemia | Pathophysiological mechanism | Animal/cellular model | References |
|---|---|---|---|
| GALK deficiency | Galactitol accumulation | Mouse | Ai et al26 |
| GALT deficiency | Accumulation of metabolites (galactose, Gal‐1‐P, galactitol, galactonate) |
Patient cell lines (SV40‐transformed fibroblasts) Saccharomyces cerevisiae Mouse
Drosophila melanogaster Danio rerio |
Lai et al5
Ross et al33 Leslie et al25; Ning et al38, 39; Yager et al41; Wehrli et al40; Tang et al30 Kushner et al27; Ryan et al44; Daenzer et al34 Vanoevelen et al31 |
| Abnormalities in UDP‐Gal and UDP‐Glc levelsa | Saccharomyces cerevisiae | Chhay et al50 | |
| Aberrant glycosylation |
Patient cell lines (fibroblasts)
Patient cell lines (SV40‐transformed fibroblasts) Patient cell lines (lymphoblasts) Drosophila melanogaster |
Dobbie et al7; Ornstein et al8; Coss et al4; Staubach et al56 Lai et al5
Petry et al57 |
|
| Down‐regulation of PI3K/Akt pathway | Mouse | Balakrishnan et al60, 61; Chen et al62 | |
| ER stress/Unfolded protein response | Saccharomyces cerevisiae | Slepak et al63; De‐Souza et al64 | |
| Patient cell lines (fibroblasts) | Slepak et al65; Staubach et al56 | ||
| Mouse | Balakrishnan et al61; Chen et al62 | ||
| Oxidative stress | Drosophila melanogaster | Jumbo‐Lucioni et al66, 67 | |
| Mouse | Tang et al30 | ||
| Structural/functional defects | Saccharomyces cerevisiae | McCorvie et al68 | |
| Escherichia coli | Coelho et al22 | ||
| GALE deficiency | Gal‐1‐P accumulation | Saccharomyces cerevisiae | Wohlers and Fridovich‐Keil45; Ross et al33; Mumma et al46 |
| Abnormalities in UDP‐hexoses levels | ldlD cells | Schulz et al69 | |
| Saccharomyces cerevisiae | Ross et al33 | ||
| Caenorhabditis elegans | Brokate‐Llanos et al29 | ||
| Drosophila melanogaster | Daenzer et al70; Jumbo‐Lucioni et al59 | ||
| ER stress | Caenorhabditis elegans | Brokate‐Llanos et al29 | |
| Structural/functional defects | Saccharomyces cerevisiae | McCorvie et al71 | |
| Escherichia coli | Pey et al.72 |
Abbreviations: ER, endoplasmic reticulum; GALE, uridine diphosphate‐galactose 4′‐epimerase; GALK, galactokinase; UDP‐Gal, uridine diphosphate‐galactose, UDP‐Glc, uridine diphosphate‐glucose.
A separate table (Table 3) is provided for UDP‐hexoses studies in different patient cell lines.