MCID: MGL012
MIFTS: 29

Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Blood diseases

Aliases & Classifications for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

MalaCards integrated aliases for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:

Name: Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency 57 53 75 29 13 6 40 73
Dhfr Deficiency 57 53 59 75
Constitutional Megaloblastic Anemia with Severe Neurologic Disease 53 59
Dihydrofolate Reductase Deficiency 53 59
Deficiency of Dihydrofolate Reductase 73
Dihydrofolate Reductase Deficiency 37
Dihydrofolate Reductase 13
Dhfrd 75

Characteristics:

Orphanet epidemiological data:

59
constitutional megaloblastic anemia with severe neurologic disease
Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
severe form with onset at 3 to 4 months of age and severe developmental delay
milder form with onset in childhood, absence seizures, and learning difficulties
treatment with folinic acid offers some benefit for anemia and seizure control


HPO:

32
megaloblastic anemia due to dihydrofolate reductase deficiency:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

UniProtKB/Swiss-Prot : 75 Megaloblastic anemia due to dihydrofolate reductase deficiency: An inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.

MalaCards based summary : Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency, also known as dhfr deficiency, is related to fetal aminopterin syndrome and hyperphenylalaninemia, bh4-deficient, a, and has symptoms including ataxia, icterus and absence seizures. An important gene associated with Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency is DHFR (Dihydrofolate Reductase), and among its related pathways/superpathways are One carbon pool by folate and Folate biosynthesis. Affiliated tissues include neutrophil, and related phenotypes are jaundice and pallor

OMIM : 57 Dihydrofolate reductase deficiency is an autosomal recessive metabolic disorder characterized by the hematologic findings of megaloblastic anemia and variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy (Banka et al., 2011) to childhood absence epilepsy with learning difficulties to lack of symptoms (Cario et al., 2011). Treatment with folinic acid can ameliorate some of the symptoms. (613839)

Related Diseases for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Diseases related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 fetal aminopterin syndrome 11.3
2 hyperphenylalaninemia, bh4-deficient, a 11.2
3 neural tube defects 10.8
4 leukemia 10.5
5 malaria 10.4
6 leukemia, acute lymphoblastic 10.3
7 lymphoblastic leukemia 10.3
8 endotheliitis 10.2
9 breast cancer 10.2
10 megaloblastic anemia 10.1
11 cerebritis 9.9
12 cerebral folate deficiency 9.9

Graphical network of the top 20 diseases related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:



Diseases related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Symptoms & Phenotypes for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
ataxia
absence seizures
cerebral atrophy
poor head control
delayed myelination
more
Hematology:
pancytopenia
thrombocytopenia
megaloblastic anemia
hypersegmented neutrophils

Muscle Soft Tissue:
hypotonia

Laboratory Abnormalities:
normal serum folate
decreased csf tetrahydrofolate and 5-methyltetrahydrofolate
decreased activity of dihydrofolate reductase

Head And Neck Eyes:
icterus
eyelid myoclonus

Abdomen Liver:
hepatomegaly

Skin Nails Hair Skin:
pallor

Growth Other:
poor feeding

Head And Neck Head:
microcephaly, acquired


Clinical features from OMIM:

613839

Human phenotypes related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 jaundice 32 HP:0000952
2 pallor 32 HP:0000980
3 ataxia 32 HP:0001251
4 global developmental delay 32 HP:0001263
5 generalized hypotonia 32 HP:0001290
6 thrombocytopenia 32 HP:0001873
7 pancytopenia 32 HP:0001876
8 megaloblastic anemia 32 HP:0001889
9 cerebral atrophy 32 HP:0002059
10 absence seizures 32 HP:0002121
11 hepatomegaly 32 HP:0002240
12 poor head control 32 HP:0002421
13 postnatal microcephaly 32 HP:0005484
14 feeding difficulties 32 HP:0011968
15 delayed myelination 32 HP:0012448
16 eyelid myoclonus 32 HP:0025097

UMLS symptoms related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:


ataxia, icterus, absence seizures

Drugs & Therapeutics for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Search Clinical Trials , NIH Clinical Center for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Genetic Tests for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Genetic tests related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:

# Genetic test Affiliating Genes
1 Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency 29 DHFR

Anatomical Context for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

MalaCards organs/tissues related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:

41
Neutrophil

Publications for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Articles related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:

# Title Authors Year
1
Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency. ( 21310276 )
2011
2
Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. ( 21310277 )
2011
3
Conditional dihydrofolate reductase deficiency due to transposon Tn5tac1 insertion downstream from the folA gene in Escherichia coli. ( 8383626 )
1993
4
Hereditary dihydrofolate reductase deficiency with megaloblastic anemia. ( 4080268 )
1985
5
Dihydrofolate reductase deficiency causing megaloblastic anemia in two families. ( 1060915 )
1976

Variations for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:

75
# Symbol AA change Variation ID SNP ID
1 DHFR p.Leu80Phe VAR_065818 rs387906619
2 DHFR p.Asp153Val VAR_065819 rs121913223

ClinVar genetic disease variations for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 DHFR NM_000791.3(DHFR): c.238C> T (p.Leu80Phe) single nucleotide variant Pathogenic rs387906619 GRCh37 Chromosome 5, 79945212: 79945212
2 DHFR NM_000791.3(DHFR): c.238C> T (p.Leu80Phe) single nucleotide variant Pathogenic rs387906619 GRCh38 Chromosome 5, 80649393: 80649393
3 DHFR NM_000791.3(DHFR): c.458A> T (p.Asp153Val) single nucleotide variant Pathogenic rs121913223 GRCh37 Chromosome 5, 79929723: 79929723
4 DHFR NM_000791.3(DHFR): c.458A> T (p.Asp153Val) single nucleotide variant Pathogenic rs121913223 GRCh38 Chromosome 5, 80633904: 80633904

Expression for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Search GEO for disease gene expression data for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency.

Pathways for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Pathways related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 One carbon pool by folate hsa00670
2 Folate biosynthesis hsa00790

GO Terms for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Sources for Megaloblastic Anemia Due to Dihydrofolate Reductase 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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