Galactosemia

Summary

Galactosemia (MONDO:0018116) is a disease caused by GALT (GenCC Definitive), with 1 cohort gene and 7 clinical trials. Top therapeutic interventions include follitropin.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: GALT (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 312
• Clinical trials: 7

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	2.1	Europe	Validated
Prevalence at birth	1-9 / 100 000	2	Europe	Validated
Prevalence at birth	1-9 / 100 000	1.3	United States	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	galactosemia
Mondo ID	MONDO:0018116
MeSH	D005693
OMIM	230400
Orphanet	352
DOID	DOID:9870
ICD-10-CM	E74.21
NCIT	C84723
SNOMED CT	190745006
UMLS	C0016952
MedGen	8943
GARD	0002424
MedDRA	10017604
NORD	1170
Is cancer (heuristic)	no

Also known as: galactosemia

Data availability: 312 ClinVar variants · 1 ClinGen variant curation · 1 GenCC gene-disease record · 43 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › galactosemia

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Subtypes (4): galactokinase deficiency, galactose epimerase deficiency, classic galactosemia, galactosemia 4

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

312 retrieved; paginated sample, class counts are floors:

84 pathogenic/likely pathogenic, 76 uncertain significance, 63 likely pathogenic, 34 pathogenic, 34 conflicting classifications of pathogenicity, 14 likely benign, 3 benign/likely benign, 2 benign, 1 conflicting classifications of pathogenicity; other, 1 benign; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066673	NM_000155.4(GALT):c.428C>G (p.Ser143Trp)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073718	NM_000155.4(GALT):c.814del (p.Arg272fs)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332995	NM_000155.4(GALT):c.200del (p.Arg67fs)	GALT	Pathogenic	criteria provided, multiple submitters, no conflicts
1378874	NM_000155.4(GALT):c.576_589del (p.Ser192fs)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457366	NM_000155.4(GALT):c.462G>A (p.Trp154Ter)	GALT	Pathogenic	criteria provided, multiple submitters, no conflicts
1458107	NM_000155.4(GALT):c.894G>A (p.Met298Ile)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458954	NM_000155.4(GALT):c.425T>C (p.Met142Thr)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1470556	NM_000155.4(GALT):c.152G>T (p.Arg51Leu)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691431	NM_000155.4(GALT):c.1001A>G (p.Lys334Arg)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1722333	NM_000155.4(GALT):c.213dup (p.Asn72fs)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189191	NM_000155.4(GALT):c.775C>T (p.Arg259Trp)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
193559	NM_000155.4(GALT):c.1052del (p.Pro351fs)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
193560	NM_000155.4(GALT):c.905-1G>A	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1992665	NM_000155.4(GALT):c.328+2T>G	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1999214	NM_000155.4(GALT):c.550del (p.His184fs)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
203733	NM_000155.4(GALT):c.200G>A (p.Arg67His)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
203734	NM_000155.4(GALT):c.367C>T (p.Arg123Ter)	GALT	Pathogenic	criteria provided, multiple submitters, no conflicts
2136755	NM_000155.4(GALT):c.368G>A (p.Arg123Gln)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136758	NM_000155.4(GALT):c.813G>C (p.Glu271Asp)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136762	NM_000155.4(GALT):c.1138T>C (p.Ter380Arg)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2180399	NM_000155.4(GALT):c.719_728del (p.Leu240fs)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
25112	NM_000155.4(GALT):c.1A>G (p.Met1Val)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
25113	NM_000155.4(GALT):c.18del (p.Asp7fs)	GALT	Pathogenic	criteria provided, multiple submitters, no conflicts
25117	NM_000155.4(GALT):c.41delinsTT (p.Ala14fs)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
25124	NM_000155.4(GALT):c.98G>A (p.Arg33His)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
25125	NM_000155.4(GALT):c.100T>A (p.Tyr34Asn)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
25137	NM_000155.4(GALT):c.199C>T (p.Arg67Cys)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
25142	NM_000155.4(GALT):c.253-2A>G	GALT	Pathogenic	criteria provided, multiple submitters, no conflicts
25146	NM_000155.4(GALT):c.290A>G (p.Asn97Ser)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
25147	NM_000155.4(GALT):c.367C>G (p.Arg123Gly)	GALT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GALT	Definitive	Autosomal recessive	galactosemia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GALT	Orphanet:79239	Classic galactosemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GALT	HGNC:4135	ENSG00000213930	P07902	Galactose-1-phosphate uridylyltransferase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GALT	Galactose-1-phosphate uridylyltransferase	Plays an important role in galactose metabolism.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GALT	Enzyme (other)	yes	2.7.7.12	GalP_UDPtransf1, GalP_Utransf_N, GalP_Utransf_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
right adrenal gland	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GALT	225	ubiquitous	marker	right lobe of liver, right adrenal gland, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GALT	708

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GALT	P07902	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective GALT can cause GALCT	1	11420.0×	2e-04	GALT
Galactose catabolism	1	1631.4×	6e-04	GALT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
UDP-alpha-D-glucose metabolic process	1	5617.3×	4e-04	GALT
beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	1	3370.4×	4e-04	GALT
galactose metabolic process	1	2106.5×	5e-04	GALT

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Govorestat	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GALT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GALT	2.7.7.12	UDP-glucose-hexose-1-phosphate uridylyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	GALT
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GALT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04948658	Not specified	RECRUITING	Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
NCT07461519	Not specified	RECRUITING	Gonadic Function and Pubertal Development in Female Patients With Classic Galactosemia
NCT00309400	Not specified	COMPLETED	The Early History of Universal Screening for Metabolic Disorders
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT02091128	Not specified	COMPLETED	Pregnancy Chances in Classic Galactosemia
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FOLLITROPIN	4	1