MCID: GLC011
MIFTS: 45

Galactose Epimerase Deficiency

Categories: Genetic diseases, Rare diseases, Eye diseases, Liver diseases, Nephrological diseases, Metabolic diseases

Aliases & Classifications for Galactose Epimerase Deficiency

MalaCards integrated aliases for Galactose Epimerase Deficiency:

Name: Galactose Epimerase Deficiency 57 53 59 37 13 40
Udp-Galactose-4-Epimerase Deficiency 57 76 53 59
Gale Deficiency 57 53 59 55
Galactosemia Type 3 59 75
Uridine Diphosphate Galactose-4-Epimerase Deficiency 59
Udpglucose 4-Epimerase Deficiency Disease 73
Epimerase Deficiency Galactosemia 59
Epimerase-Deficiency Galactosemia 75
Classical Galactosemia 73
Galactosemia Iii 57
Galactosemia 3 53
Gale-D 59
Edg 75

Characteristics:

Orphanet epidemiological data:

59
galactose epimerase deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
udp-galactose-4-epimerase deficiency in circulating blood cells only ('peripheral' or 'mild' form, usually asymptomatic)


HPO:

32
galactose epimerase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Galactose Epimerase Deficiency

OMIM : 57 Epimerase-deficiency galactosemia was originally described as a benign condition in which GALE impairment is restricted to circulating red and white blood cells (Gitzelmann, 1972). Fibroblasts, liver, phytohemagglutinin-stimulated leukocyes, and Epstein Barr virus-transformed lymphoblasts from these patients all demonstrated normal or near-normal levels of GALE, leading to the designation 'peripheral' (or 'isolated') epimerase deficiency. A second form of epimerase deficiency became apparent in which a patient, despite normal GALT activity, presented with symptoms reminiscent of classic galactosemia and demonstrated severely impaired GALE activity in both red blood cells and fibroblasts (Holton et al., 1981). This form was designated 'generalized' epimerase deficiency. Openo et al. (2006) demonstrated that epimerase deficiency is in fact not a binary condition but is, rather, a continuum disorder. GALE encodes the third enzyme in the Leloir pathway of galactose metabolism. Galactosemia I is classic galactosemia (230400), caused by deficiency of the second enzyme in the Leloir pathway, galactose-1-phosphate uridylyl-transferase (GALT; 606999). Galactosemia II (230200) is caused by deficiency of the first enzyme in the Leloir pathway, galactokinase (GALK; 604313). (230350)

MalaCards based summary : Galactose Epimerase Deficiency, also known as udp-galactose-4-epimerase deficiency, is related to epimerase deficiency galactosemia and galactosemia, and has symptoms including diarrhea, vomiting and icterus. An important gene associated with Galactose Epimerase Deficiency is GALE (UDP-Galactose-4-Epimerase), and among its related pathways/superpathways are Galactose metabolism and Glycosaminoglycan metabolism. The drugs Follicle Stimulating Hormone and Hormone Antagonists have been mentioned in the context of this disorder. Affiliated tissues include liver, breast and eye, and related phenotypes are cataract and jaundice

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79238Disease definitionGalactose epimerase deficiency is a very rare, moderate to severe form of galactosemia (see this term) characterized by moderate to severe signs of impaired galactose metabolism.EpidemiologyOverall prevalence is not known but the disorder is thought to be very rare. Annual incidence is not known.Clinical descriptionThe disorder represents a continuum from peripheral to generalized states with corresponding disease severity. When ingesting breast milk or lactose-containing formula, patients may develop hypotonia, poor feeding, vomiting, weight loss, jaundice, hepatomegaly, splenomegaly, liver disorders, aminoaciduria, impaired growth, cataracts and cognitive deficiency. In severe cases, the disease can be life-threatening.EtiologyGalactose epimerase deficiency is caused by mutations in the GALE gene (1p36) encoding the UDP-galactose 4-epimerase enzyme.Genetic counselingGalactose epimerase deficiency is inherited in an autosomal recessive manner.PrognosisOccurrence of these symptoms can be resolved or prevented by implementing a galactose-restricted diet.Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 75 Epimerase-deficiency galactosemia: Clinical features include early-onset cataracts, liver damage, deafness and mental retardation. There are two clinically distinct forms of EDG. (1) A benign, or 'peripheral' form with no detectable GALE activity in red blood cells and characterized by mild symptoms. Some patients may suffer no symptoms beyond raised levels of galactose-1-phosphate in the blood. (2) A much rarer 'generalized' form with undetectable levels of GALE activity in all tissues and resulting in severe features such as restricted growth and mental development.

Wikipedia : 76 Galactosemia (British galactosaemia, from Greek γαλακτόζη + αίμα, meaning galactose + blood,... more...

Related Diseases for Galactose Epimerase Deficiency

Diseases related to Galactose Epimerase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 237)
# Related Disease Score Top Affiliating Genes
1 epimerase deficiency galactosemia 31.7 GALE GALK1 GALT
2 galactosemia 30.7 GALE GALK1 GALT
3 cataract 27.7 GALK1 GALT
4 generalized galactose epimerase deficiency 12.2
5 erythrocyte galactose epimerase deficiency 12.2
6 melanoma 11.2
7 developmental dysplasia of the hip 1 11.1
8 exudative vitreoretinopathy 11.0
9 spondylometaphyseal dysplasia, corner fracture type 10.9
10 gillespie syndrome 10.9
11 nail disorder, nonsyndromic congenital, 8 10.9
12 cataract 1, multiple types 10.7
13 kabuki syndrome 1 10.7
14 nail disorder, nonsyndromic congenital, 2 10.7
15 lentigines 10.7
16 lymphedema-distichiasis syndrome 10.7
17 nail disorder, nonsyndromic congenital, 5 10.7
18 lipoid proteinosis of urbach and wiethe 10.7
19 cataract 10, multiple types 10.7
20 cataract 14, multiple types 10.7
21 cataract 23, multiple types 10.7
22 tuberculoid leprosy 10.7
23 breast cyst 10.7
24 hordeolum externum 10.7
25 acral lentiginous melanoma 10.7
26 aphthous stomatitis 10.7
27 hordeolum 10.7
28 ichthyosis linearis circumflexa 10.7
29 leukoplakia 10.7
30 endotheliitis 9.9
31 cerebritis 9.9
32 autoimmune disease 9.8
33 aging 9.8
34 autoimmune disease 1 9.8
35 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 9.8
36 arthritis 9.8
37 retinitis 9.8
38 neuronitis 9.8
39 malaria 9.8
40 hepatitis 9.8
41 ischemia 9.8
42 type i 9.8
43 hypoxia 9.8
44 colorectal cancer 9.7
45 wiskott-aldrich syndrome 9.7
46 keratoconus 9.7
47 esophagitis 9.7
48 prostatitis 9.7
49 squamous cell carcinoma 9.7
50 macular holes 9.7

Graphical network of the top 20 diseases related to Galactose Epimerase Deficiency:



Diseases related to Galactose Epimerase Deficiency

Symptoms & Phenotypes for Galactose Epimerase Deficiency

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Abdomen Liver:
hepatomegaly

Laboratory Abnormalities:
aminoaciduria
galactosuria
galactosemia
udp-galactose-4-epimerase deficiency in all cells ('generalized' or 'severe' form)

Neurologic Central Nervous System:
hypotonia
mental retardation
language delay
developmental delay, gross motor
cognitive delay

AbdomenSpleen:
splenomegaly

Abdomen Gastrointestinal:
vomiting

Skin Nails Hair Skin:
jaundice

Head And Neck Ears:
deafness, sensorineural


Clinical features from OMIM:

230350

Human phenotypes related to Galactose Epimerase Deficiency:

59 32 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cataract 59 32 hallmark (90%) Very frequent (99-80%) HP:0000518
2 jaundice 59 32 hallmark (90%) Very frequent (99-80%) HP:0000952
3 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
4 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
5 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
6 growth delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001510
7 splenomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001744
8 weight loss 59 32 hallmark (90%) Very frequent (99-80%) HP:0001824
9 nausea and vomiting 59 32 hallmark (90%) Very frequent (99-80%) HP:0002017
10 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
11 aminoaciduria 59 32 hallmark (90%) Very frequent (99-80%) HP:0003355
12 impairment of galactose metabolism 59 32 hallmark (90%) Very frequent (99-80%) HP:0004915
13 feeding difficulties 59 32 hallmark (90%) Very frequent (99-80%) HP:0011968
14 sensorineural hearing impairment 32 HP:0000407
15 delayed speech and language development 32 HP:0000750
16 generalized hypotonia 32 HP:0001290
17 failure to thrive 32 HP:0001508
18 vomiting 32 HP:0002013
19 delayed gross motor development 32 HP:0002194
20 galactosuria 32 HP:0012023
21 hypergalactosemia 32 HP:0012024

UMLS symptoms related to Galactose Epimerase Deficiency:


diarrhea, vomiting, icterus

GenomeRNAi Phenotypes related to Galactose Epimerase Deficiency according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased IL-8 secretion GR00386-A-2 8.8 GALK1 GALT GALE

Drugs & Therapeutics for Galactose Epimerase Deficiency

Drugs for Galactose Epimerase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Follicle Stimulating Hormone Not Applicable
2 Hormone Antagonists Not Applicable
3 Hormones Not Applicable
4 Hormones, Hormone Substitutes, and Hormone Antagonists Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Effect of Arginine on Classic Galactosemia Active, not recruiting NCT03580122 Phase 2 Arginine Aspartate
2 Inactive FSH in Galactosemia Unknown status NCT00619333 Not Applicable follitropin and lutropin
3 Glycosylation in Patients With Galactosaemia Completed NCT02218632 Not Applicable
4 Intervention and Outcomes in Duarte Galactosemia Completed NCT02519504
5 Pregnancy Chances in Classic Galactosemia Completed NCT02091128
6 The Early History of Universal Screening for Metabolic Disorders Completed NCT00309400
7 Retrospective Study of Adult Patients With Inborn Errors of Metabolism in Switzerland Recruiting NCT03534752

Search NIH Clinical Center for Galactose Epimerase Deficiency

Genetic Tests for Galactose Epimerase Deficiency

Anatomical Context for Galactose Epimerase Deficiency

MalaCards organs/tissues related to Galactose Epimerase Deficiency:

41
Liver, Breast, Eye

Publications for Galactose Epimerase Deficiency

Articles related to Galactose Epimerase Deficiency:

# Title Authors Year
1
Galactose Epimerase Deficiency: Expanding the Phenotype. ( 28247339 )
2017

Variations for Galactose Epimerase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Galactose Epimerase Deficiency:

75 (show all 16)
# Symbol AA change Variation ID SNP ID
1 GALE p.Asn34Ser VAR_002539 rs121908046
2 GALE p.Gly90Glu VAR_002540 rs28940882
3 GALE p.Asp103Gly VAR_002541 rs28940883
4 GALE p.Leu183Pro VAR_002543 rs121908045
5 GALE p.Lys257Arg VAR_002544 rs28940884
6 GALE p.Leu313Met VAR_002545 rs3180383
7 GALE p.Gly319Glu VAR_002546 rs28940885
8 GALE p.Val94Met VAR_010058 rs121908047
9 GALE p.Ala25Val VAR_037733
10 GALE p.Arg40Cys VAR_037734 rs144492228
11 GALE p.Asp69Glu VAR_037735
12 GALE p.Glu165Lys VAR_037736 rs528467258
13 GALE p.Arg169Trp VAR_037737 rs137853859
14 GALE p.Arg239Trp VAR_037738 rs137853860
15 GALE p.Gly302Asp VAR_037739 rs137853861
16 GALE p.Arg335His VAR_037740 rs368637540

ClinVar genetic disease variations for Galactose Epimerase Deficiency:

6
(show top 50) (show all 68)
# Gene Variation Type Significance SNP ID Assembly Location
1 GALE NM_000403.3(GALE): c.548T> C (p.Leu183Pro) single nucleotide variant Pathogenic rs121908045 GRCh37 Chromosome 1, 24123618: 24123618
2 GALE NM_000403.3(GALE): c.548T> C (p.Leu183Pro) single nucleotide variant Pathogenic rs121908045 GRCh38 Chromosome 1, 23797128: 23797128
3 GALE NM_000403.3(GALE): c.101A> G (p.Asn34Ser) single nucleotide variant Pathogenic rs121908046 GRCh37 Chromosome 1, 24125397: 24125397
4 GALE NM_000403.3(GALE): c.101A> G (p.Asn34Ser) single nucleotide variant Pathogenic rs121908046 GRCh38 Chromosome 1, 23798907: 23798907
5 GALE NM_000403.3(GALE): c.269G> A (p.Gly90Glu) single nucleotide variant Pathogenic rs28940882 GRCh37 Chromosome 1, 24124689: 24124689
6 GALE NM_000403.3(GALE): c.269G> A (p.Gly90Glu) single nucleotide variant Pathogenic rs28940882 GRCh38 Chromosome 1, 23798199: 23798199
7 GALE NM_001008216.1(GALE): c.308A> G (p.Asp103Gly) single nucleotide variant Pathogenic rs28940883 GRCh37 Chromosome 1, 24124650: 24124650
8 GALE NM_001008216.1(GALE): c.308A> G (p.Asp103Gly) single nucleotide variant Pathogenic rs28940883 GRCh38 Chromosome 1, 23798160: 23798160
9 GALE NM_001008216.1(GALE): c.937C> A (p.Leu313Met) single nucleotide variant Pathogenic rs3180383 GRCh37 Chromosome 1, 24122692: 24122692
10 GALE NM_001008216.1(GALE): c.937C> A (p.Leu313Met) single nucleotide variant Pathogenic rs3180383 GRCh38 Chromosome 1, 23796202: 23796202
11 GALE NM_000403.3(GALE): c.280G> A (p.Val94Met) single nucleotide variant Pathogenic/Likely pathogenic rs121908047 GRCh37 Chromosome 1, 24124678: 24124678
12 GALE NM_000403.3(GALE): c.280G> A (p.Val94Met) single nucleotide variant Pathogenic/Likely pathogenic rs121908047 GRCh38 Chromosome 1, 23798188: 23798188
13 GALE NM_000403.3(GALE): c.505C> T (p.Arg169Trp) single nucleotide variant Pathogenic rs137853859 GRCh37 Chromosome 1, 24124208: 24124208
14 GALE NM_000403.3(GALE): c.505C> T (p.Arg169Trp) single nucleotide variant Pathogenic rs137853859 GRCh38 Chromosome 1, 23797718: 23797718
15 GALE NM_000403.3(GALE): c.715C> T (p.Arg239Trp) single nucleotide variant Likely pathogenic rs137853860 GRCh37 Chromosome 1, 24123267: 24123267
16 GALE NM_000403.3(GALE): c.715C> T (p.Arg239Trp) single nucleotide variant Likely pathogenic rs137853860 GRCh38 Chromosome 1, 23796777: 23796777
17 GALE NM_000403.3(GALE): c.905G> A (p.Gly302Asp) single nucleotide variant Pathogenic rs137853861 GRCh37 Chromosome 1, 24122724: 24122724
18 GALE NM_000403.3(GALE): c.905G> A (p.Gly302Asp) single nucleotide variant Pathogenic rs137853861 GRCh38 Chromosome 1, 23796234: 23796234
19 GALE NM_000403.3(GALE): c.97G> A (p.Asp33Asn) single nucleotide variant Uncertain significance rs727503945 GRCh37 Chromosome 1, 24125401: 24125401
20 GALE NM_000403.3(GALE): c.97G> A (p.Asp33Asn) single nucleotide variant Uncertain significance rs727503945 GRCh38 Chromosome 1, 23798911: 23798911
21 GALE NM_001008216.1(GALE): c.408C> A (p.Tyr136Ter) single nucleotide variant Pathogenic rs727503943 GRCh37 Chromosome 1, 24124305: 24124305
22 GALE NM_001008216.1(GALE): c.408C> A (p.Tyr136Ter) single nucleotide variant Pathogenic rs727503943 GRCh38 Chromosome 1, 23797815: 23797815
23 GALE NM_001008216.1(GALE): c.272delT (p.Leu91Profs) deletion Pathogenic rs794727702 GRCh37 Chromosome 1, 24124686: 24124686
24 GALE NM_001008216.1(GALE): c.272delT (p.Leu91Profs) deletion Pathogenic rs794727702 GRCh38 Chromosome 1, 23798196: 23798196
25 GALE NM_001008216.1(GALE): c.796-1G> T single nucleotide variant Pathogenic rs779828095 GRCh37 Chromosome 1, 24123077: 24123077
26 GALE NM_001008216.1(GALE): c.796-1G> T single nucleotide variant Pathogenic rs779828095 GRCh38 Chromosome 1, 23796587: 23796587
27 GALE NM_000403.3(GALE): c.*327A> T single nucleotide variant Uncertain significance rs535702110 GRCh38 Chromosome 1, 23795622: 23795622
28 GALE NM_000403.3(GALE): c.*327A> T single nucleotide variant Uncertain significance rs535702110 GRCh37 Chromosome 1, 24122112: 24122112
29 GALE NM_000403.3(GALE): c.955G> C (p.Gly319Arg) single nucleotide variant Uncertain significance rs752384408 GRCh38 Chromosome 1, 23796184: 23796184
30 GALE NM_000403.3(GALE): c.955G> C (p.Gly319Arg) single nucleotide variant Uncertain significance rs752384408 GRCh37 Chromosome 1, 24122674: 24122674
31 GALE NM_000403.3(GALE): c.648G> A (p.Ala216=) single nucleotide variant Uncertain significance rs144723215 GRCh38 Chromosome 1, 23796937: 23796937
32 GALE NM_000403.3(GALE): c.648G> A (p.Ala216=) single nucleotide variant Uncertain significance rs144723215 GRCh37 Chromosome 1, 24123427: 24123427
33 GALE NM_000403.3(GALE): c.506G> A (p.Arg169Gln) single nucleotide variant Uncertain significance rs140878602 GRCh38 Chromosome 1, 23797717: 23797717
34 GALE NM_000403.3(GALE): c.506G> A (p.Arg169Gln) single nucleotide variant Uncertain significance rs140878602 GRCh37 Chromosome 1, 24124207: 24124207
35 GALE NM_000403.3(GALE): c.450G> A (p.Thr150=) single nucleotide variant Uncertain significance rs566884215 GRCh37 Chromosome 1, 24124263: 24124263
36 GALE NM_000403.3(GALE): c.450G> A (p.Thr150=) single nucleotide variant Uncertain significance rs566884215 GRCh38 Chromosome 1, 23797773: 23797773
37 GALE NM_000403.3(GALE): c.423C> T (p.Tyr141=) single nucleotide variant Uncertain significance rs138518245 GRCh37 Chromosome 1, 24124290: 24124290
38 GALE NM_000403.3(GALE): c.423C> T (p.Tyr141=) single nucleotide variant Uncertain significance rs138518245 GRCh38 Chromosome 1, 23797800: 23797800
39 GALE NM_000403.3(GALE): c.873+13_873+14insA insertion Uncertain significance rs765063773 GRCh38 Chromosome 1, 23796495: 23796496
40 GALE NM_000403.3(GALE): c.873+13_873+14insA insertion Uncertain significance rs765063773 GRCh37 Chromosome 1, 24122985: 24122986
41 GALE NM_000403.3(GALE): c.647C> T (p.Ala216Val) single nucleotide variant Uncertain significance rs542192037 GRCh38 Chromosome 1, 23796938: 23796938
42 GALE NM_000403.3(GALE): c.647C> T (p.Ala216Val) single nucleotide variant Uncertain significance rs542192037 GRCh37 Chromosome 1, 24123428: 24123428
43 GALE NM_000403.3(GALE): c.369G> A (p.Gly123=) single nucleotide variant Uncertain significance rs138148991 GRCh38 Chromosome 1, 23797854: 23797854
44 GALE NM_000403.3(GALE): c.369G> A (p.Gly123=) single nucleotide variant Uncertain significance rs138148991 GRCh37 Chromosome 1, 24124344: 24124344
45 GALE NM_000403.3(GALE): c.-161C> G single nucleotide variant Uncertain significance rs566996145 GRCh38 Chromosome 1, 23800471: 23800471
46 GALE NM_000403.3(GALE): c.-161C> G single nucleotide variant Uncertain significance rs566996145 GRCh37 Chromosome 1, 24126961: 24126961
47 GALE NM_000403.3(GALE): c.*326_*328dupTAA duplication Uncertain significance rs557214506 GRCh38 Chromosome 1, 23795621: 23795623
48 GALE NM_000403.3(GALE): c.*326_*328dupTAA duplication Uncertain significance rs557214506 GRCh37 Chromosome 1, 24122111: 24122113
49 GALE NM_000403.3(GALE): c.923A> G (p.Tyr308Cys) single nucleotide variant Uncertain significance rs780393850 GRCh37 Chromosome 1, 24122706: 24122706
50 GALE NM_000403.3(GALE): c.923A> G (p.Tyr308Cys) single nucleotide variant Uncertain significance rs780393850 GRCh38 Chromosome 1, 23796216: 23796216

Expression for Galactose Epimerase Deficiency

Search GEO for disease gene expression data for Galactose Epimerase Deficiency.

Pathways for Galactose Epimerase Deficiency

Pathways related to Galactose Epimerase Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Galactose metabolism hsa00052

GO Terms for Galactose Epimerase Deficiency

Biological processes related to Galactose Epimerase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 carbohydrate metabolic process GO:0005975 9.33 GALE GALK1 GALT
2 galactose metabolic process GO:0006012 9.13 GALE GALK1 GALT
3 galactose catabolic process GO:0019388 8.8 GALE GALK1 GALT

Sources for Galactose Epimerase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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