MCID: FRC011
MIFTS: 46

Fructose Intolerance, Hereditary

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

Aliases & Classifications for Fructose Intolerance, Hereditary

MalaCards integrated aliases for Fructose Intolerance, Hereditary:

Name: Fructose Intolerance, Hereditary 54 50
Hereditary Fructose Intolerance 23 50 24 25 56 71 52
Hereditary Fructose Intolerance Syndrome 12 14 69
Fructose Intolerance 25 13 42
Fructosemia 12 24 25
Fructose-1,6-Bisphosphate Aldolase B Deficiency 12 50
Fructose-1-Phosphate Aldolase Deficiency 50 25
Aldolase B Deficiency 50 25
Aldob Deficiency 50 25
Hereditary Fructose-1-Phosphate Aldolase Deficiency 56
Fructose-1,6-Biphosphate Aldolase Deficiency 25
Fructose Aldolase B Deficiency 25
Hereditary Fructosemia 56
Fructosaemia 12
Hfi 71

Characteristics:

Orphanet epidemiological data:

56
hereditary fructose intolerance
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy after weaning
symptoms can be prevented by strict dietary restriction
persistent exposure to fructose leads to chronic liver and kidney complications
some patients with heterozygous mutations may be symptomatic


HPO:

32
fructose intolerance, hereditary:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Fructose Intolerance, Hereditary

NIH Rare Diseases : 50 hereditary fructose intolerance (hfi) is a metabolic disease caused by the absence of an enzyme called aldolase b. in people with hfi, ingestion of fructose (fruit sugar) and sucrose (cane or beet sugar, table sugar) causes severe hypoglycemia (low blood sugar) and the build up of dangerous substances in the liver. hfi may be relatively mild or a very severe disease. the condition is caused by mutations in the aldob gene. it is inherited in an autosomal recessive pattern. treatment involves eliminating fructose and sucrose from the diet. in the severe form, eliminating these sugars from the diet may not prevent progressive liver disease. last updated: 8/20/2015

MalaCards based summary : Fructose Intolerance, Hereditary, also known as hereditary fructose intolerance, is related to bile acid synthesis defect, congenital, 2 and bile acid synthesis defect, congenital, 1, and has symptoms including failure to thrive, hepatomegaly and jaundice. An important gene associated with Fructose Intolerance, Hereditary is ALDOB (Aldolase, Fructose-Bisphosphate B), and among its related pathways/superpathways are Influenza A and WNT Signaling. The drugs Pharmaceutical Solutions and Pancrelipase have been mentioned in the context of this disorder. Affiliated tissues include liver, kidney and testes, and related phenotypes are Decreased substrate adherent cell growth and homeostasis/metabolism

UniProtKB/Swiss-Prot : 71 Hereditary fructose intolerance: Autosomal recessive disease that results in an inability to metabolize fructose and related sugars. Complete exclusion of fructose results in dramatic recovery; however, if not treated properly, HFI subjects suffer episodes of hypoglycemia, general ill condition, and risk of death the remainder of life.

Genetics Home Reference : 25 Hereditary fructose intolerance is a condition that affects a person's ability to digest the sugar fructose. Fructose is a simple sugar found primarily in fruits. Affected individuals develop signs and symptoms of the disorder in infancy when fruits, juices, or other foods containing fructose are introduced into the diet. After ingesting fructose, individuals with hereditary fructose intolerance may experience nausea, bloating, abdominal pain, diarrhea, vomiting, and low blood sugar (hypoglycemia). Affected infants may fail to grow and gain weight at the expected rate (failure to thrive).

OMIM : 54
Fructose intolerance becomes apparent in infancy at the time of weaning, when fructose or sucrose is added to the diet. Clinical features include recurrent vomiting, abdominal pain, and hypoglycemia that may be fatal. Long-term exposure to fructose can result in liver failure, renal tubulopathy, and growth retardation. Older patients who survive infancy develop a natural avoidance of sweets and fruits. Ali et al. (1998) provided a detailed review of the biochemical, genetic, and molecular basis of aldolase B deficiency in hereditary fructose intolerance. (229600)

Wikipedia : 72 Hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism caused by a deficiency... more...

GeneReviews: NBK333439

Related Diseases for Fructose Intolerance, Hereditary

Graphical network of the top 20 diseases related to Fructose Intolerance, Hereditary:



Diseases related to Fructose Intolerance, Hereditary

Symptoms & Phenotypes for Fructose Intolerance, Hereditary

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Skin Nails & Hair- Skin:
jaundice

Metabolic Features:
metabolic acidosis
lactic acidosis

Laboratory- Abnormalities:
hypoglycemia
hyperuricemia
abnormal liver function tests
hypophosphatemia
fructosemia
more
Head And Neck- Teeth:
absent dental caries

Abdomen- Liver:
hepatomegaly
cirrhosis
hepatic steatosis

Neurologic- Central Nervous System:
seizures
lethargy
coma
mental retardation (if untreated)

Abdomen- Gastroin testinal:
vomiting
abdominal pain
nausea
malnutrition
aversion to sweets and fruit

Genitourinary- Kidneys:
proximal renal tubulopathy


Clinical features from OMIM:

229600

Human phenotypes related to Fructose Intolerance, Hereditary:

32 (show all 29)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 hepatomegaly 32 HP:0002240
3 jaundice 32 HP:0000952
4 seizures 32 HP:0001250
5 lethargy 32 HP:0001254
6 metabolic acidosis 32 HP:0001942
7 lactic acidosis 32 HP:0003128
8 hyperphosphaturia 32 HP:0003109
9 vomiting 32 HP:0002013
10 coma 32 HP:0001259
11 intellectual disability 32 HP:0001249
12 hypoglycemia 32 HP:0001943
13 cirrhosis 32 HP:0001394
14 hyperuricemia 32 HP:0002149
15 hepatic steatosis 32 HP:0001397
16 abdominal pain 32 HP:0002027
17 hyperbilirubinemia 32 HP:0002904
18 nausea 32 HP:0002018
19 malnutrition 32 HP:0004395
20 hypophosphatemia 32 HP:0002148
21 proximal renal tubular acidosis 32 HP:0002049
22 glycosuria 32 HP:0003076
23 elevated hepatic transaminases 32 HP:0002910
24 proximal tubulopathy 32 HP:0000114
25 gastrointestinal hemorrhage 32 HP:0002239
26 hyperuricosuria 32 HP:0003149
27 bicarbonaturia 32 HP:0003646
28 fructose intolerance 32 HP:0005973
29 transient aminoaciduria 32 HP:0008273

UMLS symptoms related to Fructose Intolerance, Hereditary:


abdominal pain, icterus, lethargy, nausea, seizures, vomiting

GenomeRNAi Phenotypes related to Fructose Intolerance, Hereditary according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased substrate adherent cell growth GR00193-A-1 9.61 CDK2 MAPK1
2 Decreased substrate adherent cell growth GR00193-A-2 9.61 CDK2 IRAK1
3 Decreased substrate adherent cell growth GR00193-A-3 9.61 MAPK1 CDK2 IRAK1
4 Decreased substrate adherent cell growth GR00193-A-4 9.61 MAPK1 CDK2
5 Increased cell death HMECs cells GR00103-A-0 9.1 CDK2 CLU GLUL MAPK1 PTPN1 TF

MGI Mouse Phenotypes related to Fructose Intolerance, Hereditary:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.03 GLUL HP MAPK1 PMM2 PTPN1 TALDO1
2 cellular MP:0005384 10.02 ALG2 CDK2 GLUL HP IRAK1 MANBA
3 cardiovascular system MP:0005385 9.97 CCND3 CDK2 CLU HP IRAK1 MANBA
4 immune system MP:0005387 9.85 ALDOB CCND3 CDK2 CLU HP IRAK1
5 liver/biliary system MP:0005370 9.61 ALDOB CCND3 CDK2 GLUL HP MANBA
6 mortality/aging MP:0010768 9.4 ALDOB ALG2 CCND3 CDK2 GLUL HP

Drugs & Therapeutics for Fructose Intolerance, Hereditary

Drugs for Fructose Intolerance, Hereditary (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pharmaceutical Solutions Phase 4
2
Pancrelipase Approved 53608-75-6
3 Alpha 1-Antitrypsin
4 Liver Extracts
5 pancreatin
6 Protein C Inhibitor
7
Levan 9013-95-0 22833608
8 Calcium polycarbophil
9 Cathartics
10 Gastrointestinal Agents
11 Laxatives
12 alanine Nutraceutical
13 Psyllium Nutraceutical

Interventional clinical trials:

(show all 11)

id Name Status NCT ID Phase Drugs
1 Oral Versus Intravenous Rehydration for Prevention of Dehydration in Premature Babies, During the First Days of Life. Completed NCT00715000 Phase 4
2 Is the Expression of the GLUT5 Specific Fructose Transport Protein Abnormal in Patients With Fructose Intolerance? Completed NCT01705171
3 Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance Completed NCT02979106
4 Endomicroscopy, IBS and Food Intolerance Completed NCT01692613
5 Shear Wave Sonoelastography in Pediatric Liver Fibrosis Recruiting NCT02372682
6 Investigation of Alanine in Fructose Intolerance: A Dose Ranging Study Active, not recruiting NCT01185210
7 Fructose and Lactose Intolerance and Malabsorption in Functional Gastrointestinal Disorders Active, not recruiting NCT02085889
8 FODMAP Reintroduction in Irritable Bowel Syndrome Enrolling by invitation NCT03245645
9 Fructose Breath-testing in Irritable Bowel Syndrome (IBS) Not yet recruiting NCT02614313
10 Clinical Utility of Breath Tests in GI Not yet recruiting NCT03261856
11 Long Term Fructose Terminated NCT01288495

Search NIH Clinical Center for Fructose Intolerance, Hereditary

Cochrane evidence based reviews: fructose intolerance

Genetic Tests for Fructose Intolerance, Hereditary

Genetic tests related to Fructose Intolerance, Hereditary:

id Genetic test Affiliating Genes
1 Hereditary Fructose Intolerance 24 ALDOB

Anatomical Context for Fructose Intolerance, Hereditary

MalaCards organs/tissues related to Fructose Intolerance, Hereditary:

39
Liver, Kidney, Testes

Publications for Fructose Intolerance, Hereditary

Variations for Fructose Intolerance, Hereditary

UniProtKB/Swiss-Prot genetic disease variations for Fructose Intolerance, Hereditary:

71 (show all 16)
id Symbol AA change Variation ID SNP ID
1 ALDOB p.Cys135Arg VAR_000551
2 ALDOB p.Ala150Pro VAR_000553 rs1800546
3 ALDOB p.Ala175Asp VAR_000554 rs76917243
4 ALDOB p.Leu257Pro VAR_000555 rs764701775
5 ALDOB p.Arg304Trp VAR_000556 rs555935217
6 ALDOB p.Asn335Lys VAR_000557 rs78340951
7 ALDOB p.Ala338Val VAR_000558 rs77718928
8 ALDOB p.Ile74Thr VAR_020822 rs781023784
9 ALDOB p.Pro185Arg VAR_020824
10 ALDOB p.Val222Phe VAR_020826
11 ALDOB p.Leu229Pro VAR_020827
12 ALDOB p.Arg304Gln VAR_020828 rs145078268
13 ALDOB p.Cys178Arg VAR_058211
14 ALDOB p.Leu284Pro VAR_058212
15 ALDOB p.Arg46Trp VAR_075348 rs41281039
16 ALDOB p.Tyr343His VAR_075349 rs369586696

ClinVar genetic disease variations for Fructose Intolerance, Hereditary:

6 (show all 30)
id Gene Variation Type Significance SNP ID Assembly Location
1 ALDOB NM_000035.3(ALDOB): c.448G> C (p.Ala150Pro) single nucleotide variant Pathogenic rs1800546 GRCh37 Chromosome 9, 104189856: 104189856
2 ALDOB NM_000035.3(ALDOB): c.524C> A (p.Ala175Asp) single nucleotide variant Pathogenic rs76917243 GRCh37 Chromosome 9, 104189780: 104189780
3 ALDOB NM_000035.3(ALDOB): c.865_867delCTT (p.Leu289del) deletion Pathogenic rs118204425 GRCh37 Chromosome 9, 104187257: 104187259
4 ALDOB NM_000035.3(ALDOB): c.720C> A (p.Cys240Ter) single nucleotide variant Pathogenic rs118204426 GRCh37 Chromosome 9, 104187814: 104187814
5 ALDOB NM_000035.3(ALDOB): c.1005C> G (p.Asn335Lys) single nucleotide variant Pathogenic rs78340951 GRCh37 Chromosome 9, 104184181: 104184181
6 ALDOB ALDOB, 7-BP DEL/1-BP INS, 3-PRIME IVS8 indel Pathogenic
7 ALDOB NM_000035.3(ALDOB): c.10C> T (p.Arg4Ter) single nucleotide variant Pathogenic/Likely pathogenic rs118204428 GRCh37 Chromosome 9, 104193160: 104193160
8 ALDOB NM_000035.3(ALDOB): c.178C> T (p.Arg60Ter) single nucleotide variant Pathogenic/Likely pathogenic rs118204429 GRCh37 Chromosome 9, 104192183: 104192183
9 ALDOB ALDOB, IVS6AS, G-A, -1 single nucleotide variant Pathogenic
10 ALDOB NM_000035.3(ALDOB): c.547_552delCTGGTA (p.Leu183_Val184del) deletion Pathogenic rs387906226 GRCh37 Chromosome 9, 104188909: 104188914
11 ALDOB NM_000035.3(ALDOB): c.442T> C (p.Trp148Arg) single nucleotide variant Pathogenic rs118204430 GRCh37 Chromosome 9, 104189862: 104189862
12 ALDOB NM_000035.3(ALDOB): c.-10-2043_624+62del deletion Pathogenic GRCh37 Chromosome 9, 104188775: 104195222
13 ALDOB NM_000035.3(ALDOB): c.136A> T (p.Arg46Trp) single nucleotide variant Pathogenic rs41281039 GRCh37 Chromosome 9, 104192225: 104192225
14 ALDOB NM_000035.3(ALDOB): c.1027T> C (p.Tyr343His) single nucleotide variant Pathogenic rs369586696 GRCh37 Chromosome 9, 104184159: 104184159
15 ALDOB NM_000035.3(ALDOB): c.1013C> T (p.Ala338Val) single nucleotide variant Likely pathogenic rs77718928 GRCh37 Chromosome 9, 104184173: 104184173
16 ALDOB NM_000035.3(ALDOB): c.625-2A> G single nucleotide variant Likely pathogenic rs786204503 GRCh37 Chromosome 9, 104187911: 104187911
17 ALDOB NM_000035.3(ALDOB): c.612T> A (p.Tyr204Ter) single nucleotide variant Pathogenic/Likely pathogenic rs370793608 GRCh38 Chromosome 9, 101426567: 101426567
18 ALDOB NM_000035.3(ALDOB): c.360_363delCAAA (p.Asn120Lysfs) deletion Pathogenic/Likely pathogenic rs387906225 GRCh37 Chromosome 9, 104190767: 104190770
19 ALDOB NM_000035.3(ALDOB): c.324G> A (p.Lys108=) single nucleotide variant Likely pathogenic rs750026492 GRCh37 Chromosome 9, 104192037: 104192037
20 ALDOB NM_000035.3(ALDOB): c.113-1_115delGGTA deletion Likely pathogenic rs786204598 GRCh37 Chromosome 9, 104192246: 104192249
21 ALDOB NM_000035.3(ALDOB): c.865delC (p.Leu289Phefs) deletion Pathogenic rs864309533 GRCh37 Chromosome 9, 104187259: 104187259
22 ALDOB NM_000035.3(ALDOB): c.324+1G> A single nucleotide variant Pathogenic rs764826805 GRCh37 Chromosome 9, 104192036: 104192036
23 ALDOB NM_000035.3(ALDOB): c.888G> A (p.Trp296Ter) single nucleotide variant Likely pathogenic rs1057517133 GRCh38 Chromosome 9, 101424954: 101424954
24 ALDOB NM_000035.3(ALDOB): c.546delA (p.Leu183Trpfs) deletion Likely pathogenic rs1057517091 GRCh38 Chromosome 9, 101426633: 101426633
25 ALDOB NM_000035.3(ALDOB): c.444G> A (p.Trp148Ter) single nucleotide variant Likely pathogenic rs1057516902 GRCh37 Chromosome 9, 104189860: 104189860
26 ALDOB NM_000035.3(ALDOB): c.420delA (p.Asp141Metfs) deletion Likely pathogenic rs1057517421 GRCh38 Chromosome 9, 101427602: 101427602
27 ALDOB NM_000035.3(ALDOB): c.379+1G> A single nucleotide variant Likely pathogenic rs138121153 GRCh37 Chromosome 9, 104190750: 104190750
28 ALDOB NM_000035.3(ALDOB): c.324+2T> A single nucleotide variant Likely pathogenic rs1057516379 GRCh38 Chromosome 9, 101429753: 101429753
29 ALDOB NM_000035.3(ALDOB): c.112+1delG deletion Likely pathogenic rs1057516534 GRCh37 Chromosome 9, 104193057: 104193057
30 ALDOB NM_000035.3(ALDOB): c.911G> A (p.Arg304Gln) single nucleotide variant Likely pathogenic rs145078268 GRCh38 Chromosome 9, 101424931: 101424931

Expression for Fructose Intolerance, Hereditary

Search GEO for disease gene expression data for Fructose Intolerance, Hereditary.

Pathways for Fructose Intolerance, Hereditary

Pathways related to Fructose Intolerance, Hereditary according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.25 CCND3 CDK2 IRAK1 MAPK1 TRAF3
2 11.96 CCND3 CCNH CDK2 MAPK1
3 11.23 CCND3 CDK2 MAPK1 TRAF3
4 10.96 CCND3 CDK2 MAPK1
5 10.68 CDK2 MAPK1

GO Terms for Fructose Intolerance, Hereditary

Cellular components related to Fructose Intolerance, Hereditary according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.61 ALDOB CLU GLUL HP MAPK1 PMM2
2 cyclin-dependent protein kinase holoenzyme complex GO:0000307 8.62 CCND3 CDK2

Biological processes related to Fructose Intolerance, Hereditary according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 platelet degranulation GO:0002576 9.43 CLU SERPINA1 TF
2 positive regulation of receptor-mediated endocytosis GO:0048260 9.16 CLU TF
3 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 8.96 MAPK1 PTPN1
4 regulation of insulin receptor signaling pathway GO:0046626 8.62 CCND3 PTPN1

Molecular functions related to Fructose Intolerance, Hereditary according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.55 ALDOB ALG2 CCND3 CCNH CDK2 CLU
2 RNA polymerase II carboxy-terminal domain kinase activity GO:0008353 8.96 CCNH MAPK1

Sources for Fructose Intolerance, Hereditary

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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