MCID: HRD028
MIFTS: 33

Hereditary Folate Malabsorption malady

Genetic diseases, Gastrointestinal diseases, Metabolic diseases, Blood diseases, Rare diseases, Endocrine diseases categories
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Summaries for Hereditary Folate Malabsorption

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Genetics Home Reference:21 Hereditary folate malabsorption is a disorder that interferes with the body's ability to absorb certain B vitamins (called folates) from food. Folates are important for many cell functions, including the production of DNA and its chemical cousin, RNA.

MalaCards based summary: Hereditary Folate Malabsorption, is also known as congenital folate malabsorption, and has symptoms including oral mucosa disease/cheilitis, glossitis and nausea/vomiting/regurgitation/merycism/hyperemesis. An important gene associated with Hereditary Folate Malabsorption is SLC46A1 (solute carrier family 46 (folate transporter), member 1). Affiliated tissues include thyroid, bone marrow and bone.

Description from OMIM:46 229050

GeneReviews summary for folate-mal

Aliases & Classifications for Hereditary Folate Malabsorption

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Sources:
19GeneReviews, 20GeneTests, 21Genetics Home Reference, 46OMIM, 48Orphanet, 62UMLS, 26ICD10 via Orphanet
See all sources

Hereditary Folate Malabsorption, Aliases & Descriptions:

Name: Hereditary Folate Malabsorption 19 20 21 48
Congenital Folate Malabsorption 19 21 48
Congenital Defect of Folate Absorption 21 62
 
Thyroid Hormone Plasma Membrane Transport Defect 62
Folate Malabsorption, Hereditary 46
Folic Acid Transport Defect 21


Classifications:



Characteristics (Orphanet epidemiological data):

48
hereditary folate malabsorption:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy


External Ids:

OMIM46 229050
ICD10 via Orphanet26 D52.8

Related Diseases for Hereditary Folate Malabsorption

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Symptoms for Hereditary Folate Malabsorption

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Symptoms by clinical synopsis from OMIM:

229050

Clinical features from OMIM:

229050

Symptoms:

48 (show all 27)
  • oral mucosa disease/cheilitis
  • glossitis
  • nausea/vomiting/regurgitation/merycism/hyperemesis
  • malabsorption/chronic diarrhea/steatorrhea
  • movement disorder
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • anorexia
  • anomalies of the immunitary system
  • agammaglobulinemia/hypogammaglobulinemia/b-cell deficiency
  • megaloblastic anemia
  • autosomal recessive inheritance
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • pallor
  • gastroesophageal reflux/pyrosis/esophagitis/hiatal hernia/gastroparesia
  • peripheral neuropathy
  • motor deficit/trouble
  • seizures/epilepsy/absences/spasms/status epilepticus
  • psychic/behavioural troubles
  • repeat respiratory infections
  • recurrent urinary infections
  • intracranial/cerebral calcifications
  • hypereflexia
  • muscle hypotrophy/atrophy/dystrophy/agenesis/amyotrophy
  • immunodeficiency/increased susceptibility to infections/recurrent infections
  • bone marrow failure/pancytopenia
  • eosinophils anomalies/hypereosinophilia
  • thrombocytopenia/thrombopenia

HPO human phenotypes related to Hereditary Folate Malabsorption:

(show all 44)
id Description Frequency HPO Source Accession
1 glossitis hallmark (90%) HP:0000206
2 pallor hallmark (90%) HP:0000980
3 megaloblastic anemia hallmark (90%) HP:0001889
4 nausea and vomiting hallmark (90%) HP:0002017
5 malabsorption hallmark (90%) HP:0002024
6 anorexia hallmark (90%) HP:0002039
7 hypogammaglobulinemia hallmark (90%) HP:0004313
8 abnormality of movement hallmark (90%) HP:0100022
9 cognitive impairment hallmark (90%) HP:0100543
10 cheilitis hallmark (90%) HP:0100825
11 behavioral abnormality typical (50%) HP:0000708
12 seizures typical (50%) HP:0001250
13 peripheral neuropathy typical (50%) HP:0009830
14 recurrent urinary tract infections occasional (7.5%) HP:0000010
15 hyperreflexia occasional (7.5%) HP:0001347
16 thrombocytopenia occasional (7.5%) HP:0001873
17 abnormality of eosinophils occasional (7.5%) HP:0001879
18 recurrent respiratory infections occasional (7.5%) HP:0002205
19 cerebral calcification occasional (7.5%) HP:0002514
20 amyotrophy occasional (7.5%) HP:0003202
21 bone marrow hypocellularity occasional (7.5%) HP:0005528
22 autosomal recessive inheritance HP:0000007
23 oral ulcer HP:0000155
24 irritability HP:0000737
25 intellectual disability HP:0001249
26 seizures HP:0001250
27 ataxia HP:0001251
28 muscular hypotonia HP:0001252
29 global developmental delay HP:0001263
30 failure to thrive HP:0001508
31 thrombocytopenia HP:0001873
32 neutropenia HP:0001875
33 leukopenia HP:0001882
34 diarrhea HP:0002014
35 malabsorption HP:0002024
36 basal ganglia calcification HP:0002135
37 athetosis HP:0002305
38 recurrent infections HP:0002719
39 recurrent infections HP:0002719
40 infantile onset HP:0003593
41 folate-responsive megaloblastic anemia HP:0004851
42 feeding difficulties in infancy HP:0008872
43 peripheral neuropathy HP:0009830
44 dyskinesia HP:0100660

Drugs & Therapeutics for Hereditary Folate Malabsorption

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Drug clinical trials:

Search ClinicalTrials for Hereditary Folate Malabsorption

Search NIH Clinical Center for Hereditary Folate Malabsorption

Genetic Tests for Hereditary Folate Malabsorption

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Genetic tests related to Hereditary Folate Malabsorption:

id Genetic test Affiliating Genes
1 Hereditary Folate Malabsorption20 SLC46A1

Anatomical Context for Hereditary Folate Malabsorption

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MalaCards organs/tissues related to Hereditary Folate Malabsorption:

32
Thyroid, Bone marrow, Bone, B cells

Animal Models for Hereditary Folate Malabsorption or affiliated genes

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Publications for Hereditary Folate Malabsorption

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Articles related to Hereditary Folate Malabsorption:

(show all 19)
idTitleAuthorsYear
1
Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption. (24691418)
2014
2
The first Chinese case report of hereditary folate malabsorption with a novel mutation on SLC46A1. (24534056)
2014
3
A novel deletion mutation in the proton-coupled folate transporter (PCFT; SLC46A1) in a Nicaraguan child with hereditary folate malabsorption. (23816405)
2013
4
A P425R mutation of the proton-coupled folate transporter causing hereditary folate malabsorption produces a highly selective alteration in folate binding. (22345511)
2012
5
Functional roles of the A335 and G338 residues of the proton-coupled folate transporter (PCFT-SLC46A1) mutated in hereditary folate malabsorption. (22843796)
2012
6
Prevalence of a loss-of-function mutation in the proton-coupled folate transporter gene (PCFT-SLC46A1) causing hereditary folate malabsorption in Puerto Rico. (21489556)
2011
7
A mouse model of hereditary folate malabsorption: deletion of the PCFT gene leads to systemic folate deficiency. (21346251)
2011
8
Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption. (21333572)
2011
9
Properties of the Arg376 residue of the proton-coupled folate transporter (PCFT-SLC46A1) and a glutamine mutant causing hereditary folate malabsorption. (20686069)
2010
10
A novel PCFT gene mutation (p.Cys66LeufsX99) causing hereditary folate malabsorption. (20005757)
2010
11
Mutation of the proton-coupled folate transporter gene (PCFT-SLC46A1) in Turkish siblings with hereditary folate malabsorption. (20795774)
2010
12
Functional roles of aspartate residues of the proton-coupled folate transporter (PCFT-SLC46A1); a D156Y mutation causing hereditary folate malabsorption. (20805364)
2010
13
Hereditary folate malabsorption: a positively charged amino acid at position 113 of the proton-coupled folate transporter (PCFT/SLC46A1) is required for folic acid binding. (19508863)
2009
14
A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function. (18559978)
2008
15
The clinical course and genetic defect in the PCFT gene in a 27-year-old woman with hereditary folate malabsorption. (18718264)
2008
16
The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. (17446347)
2007
17
Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. (17129779)
2006
18
Hereditary folate malabsorption: family report and review of the literature. (11807405)
2002
19
Hereditary Folate Malabsorption (20301716)
1993

Variations for Hereditary Folate Malabsorption

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UniProtKB/Swiss-Prot genetic disease variations for Hereditary Folate Malabsorption:

64
id Symbol AA change Variation ID SNP ID
1SLC46A1p.Arg113SerVAR_032825rs80338770
2SLC46A1p.Gly147ArgVAR_032826rs80338771
3SLC46A1p.Ser318ArgVAR_032827rs80338772
4SLC46A1p.Arg376TrpVAR_032828rs80338773
5SLC46A1p.Pro425ArgVAR_032829rs80338774
6SLC46A1p.Arg113CysVAR_058210rs80338770
7SLC46A1p.Asp156TyrVAR_067960rs281875210
8SLC46A1p.Ala335AspVAR_067961rs281875208
9SLC46A1p.Gly338ArgVAR_067962rs281875209
10SLC46A1p.Arg376GlnVAR_067963rs281875211

Clinvar genetic disease variations for Hereditary Folate Malabsorption:

6 (show all 17)
id Gene Name Type Significance SNP ID Assembly Location
1NM_080669.5(SLC46A1): c.1274C> G (p.Pro425Arg)single nucleotide variantPathogenicrs80338774GRCh37Chr 17, 26727674: 26727674
2SLC46A1NM_080669.5(SLC46A1): c.197_198delGCinsAA (p.Cys66Ter)indelPathogenicrs154623632GRCh37Chr 17, 26732935: 26732936
3SLC46A1NM_080669.5(SLC46A1): c.439G> C (p.Gly147Arg)single nucleotide variantPathogenicrs80338771GRCh37Chr 17, 26732276: 26732276
4SLC46A1SLC46A1, 1-BP INS, 17CinsertionPathogenic
5SLC46A1NM_080669.5(SLC46A1): c.1004C> A (p.Ala335Asp)single nucleotide variantPathogenicrs281875208GRCh37Chr 17, 26731711: 26731711
6SLC46A1NM_080669.5(SLC46A1): c.204_205delCC (p.Asn68Lysfs)deletionPathogenicrs397515391GRCh37Chr 17, 26732928: 26732929
7SLC46A1NM_080669.5(SLC46A1): c.1012G> C (p.Gly338Arg)single nucleotide variantPathogenicrs281875209GRCh37Chr 17, 26731703: 26731703
8SLC46A1NM_080669.5(SLC46A1): c.1127G> A (p.Arg376Gln)single nucleotide variantPathogenicrs281875211GRCh37Chr 17, 26729294: 26729294
9SLC46A1NM_080669.5(SLC46A1): c.194dupG (p.Cys66Leufs)duplicationPathogenicrs397515573GRCh37Chr 17, 26732939: 26732939
10SLC46A1NM_080669.5(SLC46A1): c.23dupC (p.Glu9Glyfs)duplicationPathogenicrs397515574GRCh37Chr 17, 26733109: 26733110
11SLC46A1NM_080669.5(SLC46A1): c.466G> T (p.Asp156Tyr)single nucleotide variantPathogenicrs281875210GRCh37Chr 17, 26732249: 26732249
12SLC46A1NM_080669.5(SLC46A1): c.1082-1G> Asingle nucleotide variantPathogenicrs80338775GRCh37Chr 17, 26729340: 26729340
13SLC46A1NM_080669.5(SLC46A1): c.194delG (p.Gly65Alafs)deletionPathogenicrs80338769GRCh37Chr 17, 26732939: 26732939
14SLC46A1NM_080669.5(SLC46A1): c.337C> A (p.Arg113Ser)single nucleotide variantPathogenicrs80338770GRCh37Chr 17, 26732378: 26732378
15SLC46A1NM_080669.5(SLC46A1): c.954C> G (p.Ser318Arg)single nucleotide variantPathogenicrs80338772GRCh37Chr 17, 26731761: 26731761
16SLC46A1NM_080669.5(SLC46A1): c.1126C> T (p.Arg376Trp)single nucleotide variantPathogenicrs80338773GRCh37Chr 17, 26729295: 26729295
17SLC46A1NM_080669.5(SLC46A1): c.337C> T (p.Arg113Cys)single nucleotide variantPathogenicrs80338770GRCh37Chr 17, 26732378: 26732378

Expression for genes affiliated with Hereditary Folate Malabsorption

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Expression patterns in normal tissues for genes affiliated with Hereditary Folate Malabsorption

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Pathways for genes affiliated with Hereditary Folate Malabsorption

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Compounds for genes affiliated with Hereditary Folate Malabsorption

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GO Terms for genes affiliated with Hereditary Folate Malabsorption

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Biological processes related to Hereditary Folate Malabsorption according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1transmembrane transportGO:0550859.3SLC46A1, SLC37A1

Products for genes affiliated with Hereditary Folate Malabsorption

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  • Antibodies
  • Proteins
  • Lysates

Sources for Hereditary Folate Malabsorption

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet