Human Disease Model Report: galactosemia, classic

General Information

Name

galactosemia, classic

FlyBase ID

FBhh0000151

Disease Ontology Term

classic galactosemia

Parent Disease

galactosemia

OMIM

GALACTOSEMIA I; GALAC1

Overview

This report describes classic galactosemia, which is a subtype of galactosemia. Classic galactosemia is inherited as an autosomal recessive. The human gene implicated in this disease is Galactose-1-Phosphate Uridylyltransferase (GALT), which encodes an enzyme in the galactose metabolic pathway. There is a single fly ortholog, Dmel\Galt, for which classical amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

A UAS construct driving the wild-type human gene, Hsap\GALT, has been introduced into flies. Heterologous rescue (functional complementation) of the phenotypes of Dmel\Galt amorphic mutations has been demonstrated (FBrf0211713, FBrf0219906).

Amorphic alleles of Dmel\Galt (when homozygous) are lethal on the food typically used for Drosophila culture. Such mutants survive in the absence of galactose; this recapitulates a key aspect of the human disease. Even with lifelong dietary restriction of galactose, homozygotes display impaired geotactic response. Genetic interactions of Dmel\Galt have been described; see the Galt gene report.

[updated Jun. 2017 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: galactosemia

Symptoms and phenotype

Classic galactosemia (type I) is the most severe and the most common form of the condition, occurring in 1 in 30,000-60,000 newborns. If infants with classic galactosemia are not treated promptly with a low-galactose diet, life-threatening complications appear within a few days after birth. Affected infants typically develop feeding difficulties, lethargy, failure to thrive, jaundice, liver damage, and abnormal bleeding. Galactosemia type II and type III are less common and are typically less severe. [from Genetics Home Reference, Galactosemia; 2016.01.25]

(FlyBase Curators, 2013-)

Galactosemias are disorders of galactose metabolism. Symptoms vary, depending upon the enzyme affected. [from MIM:230400, MIM:230200. MIM:230350, MIM:618881; 2020.07.13]

(OMIM, 2013-)

Specific Disease Summary: galactosemia, classic

OMIM report

[GALACTOSEMIA I; GALAC1](https://omim.org/entry/230400)

Human gene(s) implicated

[GALACTOSE-1-PHOSPHATE URIDYLYLTRANSFERASE; GALT](https://omim.org/entry/606999)

Symptoms and phenotype

Most patients suffering from classic galactosemia present in the neonatal period after ingestion of galactose; symptoms include jaundice, food intolerance, susceptibility to infection, hypoglycemia, and liver damage. Long-term complications may include mental retardation, verbal dyspraxia, motor abnormalities, gonadal abnormalities, and cataracts (summary by Bosch, 2006; pubmed:6838075). [from MIM:230400; 2016.01.26]

(OMIM, 2013-)

Genetics

Classic galactosemia is inherited as an autosomal recessive; it is caused by homozygous or compound heterozygous mutation in the galactose-1-phosphate uridylyltransferase gene (GALT). [from MIM:230400; 2016.01.26]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

Galactose-1-phosphate uridylyltransferase (GALT) is an enzyme in the galactose metabolic pathway. [from MIM:606999; 2016.01.26]

(OMIM, 2013-)

External links

Gene2Function (human gene): GALT
Gene Cards: GALT
GeneReviews, NCBI Bookshelf: Classic Galactosemia and Clinical Variant Galactosemia
MedlinePlus (condition): Galactosemia
MedlinePlus (gene): GALT
MARRVEL (human gene): GALT
NCBI MedGen: Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
NCBI (Entrez) gene: GALT; galactose-1-phosphate uridylyltransferase
National Organization for Rare Disorders: Galactosemia

Disease synonyms

galactose-1-phosphate uridyltransferase deficiency

galactosemia

galactosemia I

GALT deficiency

Related Diseases

Related human health report(s)

galactose epimerase deficiency

galactosemia

Related Specific Diseases

OMIM phenotypic series

Galactosemia

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[GALAC1](https://omim.org/entry/230400)

[GALT](https://omim.org/entry/606999)

galactosemia, classic

[GALAC2](https://omim.org/entry/230200)

[GALK1](https://omim.org/entry/604313)

[GALAC3](https://omim.org/entry/230350)

[GALE](https://omim.org/entry/606953)

galactose epimerase deficiency

[GALAC4](https://omim.org/entry/618881)

[GALM](https://omim.org/entry/137030)

Ortholog Information

Human gene(s) in FlyBase

Hsap\GALT

Human gene (HGNC)

Symbol / Name

GALT; galactose-1-phosphate uridylyltransferase

D. melanogaster ortholog (based on DIOPT)

Dmel\Galt

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Galt

Gene Snapshot

Galactose-1-phosphate uridylyltransferase (Galt) encodes an enzyme that synthesizes glucose 1-phosphate and UDP-galactose from UDP-D-glucose and alpha-D-galactose 1-phosphate. It is involved in galactose metabolism. [Date last reviewed: 2024-09-19]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

URTF
GALCA

Comments on ortholog(s)

Ortholog of human gene GALT (1 Drosophila to 1 human). Dmel\Galt shares 58% identity and 73% similarity with Hsap\GALT.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (0 groups)

Alleles Reported to Model Human Disease (Disease Ontology) (6 alleles)

Galt

Models Based on Experimental Evidence ( 5 )

Allele

Disease

Evidence

References

Galt^Δ1V2

model of galactosemia

CEA

(Kushner et al., 2010)

Galt^Δ1AP2

model of galactosemia

CEA

(Jumbo-Lucioni et al., 2014, Jumbo-Lucioni et al., 2014, Jumbo-Lucioni et al., 2013, Ryan et al., 2012, Kushner et al., 2010)

model of classic galactosemia

CEA

(Daenzer et al., 2016)

Galt^C2

model of galactosemia

CEA

(Jumbo-Lucioni et al., 2013)

Galt^KK102974

model of galactosemia

CEA

(Jumbo-Lucioni et al., 2014)

Galt³

model of classic galactosemia

CEA

(Daenzer et al., 2004)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

Galt^Δ1AP2

model of galactosemia

is ameliorated by Hsap\GALT^UAS.cKa

(Jumbo-Lucioni et al., 2014, Kushner et al., 2010)

is ameliorated by Galk^ΔEXC9

(Jumbo-Lucioni et al., 2014)

is ameliorated by sgl^UY771

(Jumbo-Lucioni et al., 2014)

is exacerbated by Gale^h