Related Experiment Video
Updated: Jun 18, 2026
08:33
Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models
Published on: March 24, 2019
Galactosemia, a single gene disorder with epigenetic consequences
David J Coman1, David W Murray, Jennifer C Byrne
1National Centre for Inherited Metabolic Disorders, Children's University Hospital, Dublin 1, Ireland.
Pediatric Research
|December 3, 2009
Summary
Classic galactosemia (GAL) patients show persistent abnormal glycosylation and gene dysregulation despite dietary restriction. Long-term galactose restriction may contribute to ongoing systemic issues in treated individuals.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Long-term outcomes for classic galactosemia (GAL) patients are often poor, with unclear causes for complications.
- It remains debated whether complications stem from early toxicity or ongoing metabolic pathway disruptions.
Purpose of the Study:
- To investigate gene expression and serum glycosylation in GAL patients on a galactose-restricted diet.
- To identify molecular mechanisms underlying long-term complications in treated classic galactosemia.
Main Methods:
- Gene expression profiling (transcriptome analysis) was conducted on four GAL patients compared to controls.
- Serum N-glycan profiles and IgG glycosylation were analyzed in ten treated GAL patients using HPLC.
- Key altered genes, including SPARC and S100A8, were further examined.
Main Results:
- Significant pathway perturbations were observed in GAL patients, including MAPK signaling and ubiquitin-mediated proteolysis.
- Patients exhibited altered serum N-glycan profiles, with increased agalactosylated/monogalactosylated and decreased digalactosylated structures.
- Microarray data revealed persistent abnormal glycosylation, indicating ongoing metabolic dyshomeostasis and gene dysregulation.
Conclusions:
- Treated classic galactosemia patients exhibit persistent molecular abnormalities despite dietary galactose restriction.
- Long-term, severe dietary galactose restriction might contribute to ongoing systemic issues in GAL patients.
- Further research is needed to understand the balance between neonatal survival and long-term metabolic health in GAL.
Related Concept Videos
01:20Inborn Errors of Metabolism
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
01:27Glucose Transporters
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
02:30Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:11Genetic Lingo
Overview
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...