DHFRD
MCID: MGL012
MIFTS: 29

Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency (DHFRD)

Categories: Blood diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare 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 56 52 73 29 13 6 39 71
Dhfr Deficiency 56 52 58 73
Dihydrofolate Reductase Deficiency 52 58 36
Constitutional Megaloblastic Anemia with Severe Neurologic Disease 52 58
Deficiency of Dihydrofolate Reductase 71
Dhfrd 73

Characteristics:

Orphanet epidemiological data:

58
constitutional megaloblastic anemia with severe neurologic disease
Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM:

56
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:

31
megaloblastic anemia due to dihydrofolate reductase deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Rare haematological diseases


External Ids:

OMIM 56 613839
KEGG 36 H01197
ICD10 via Orphanet 33 D52.8
UMLS via Orphanet 72 C3151205
Orphanet 58 ORPHA319651
MedGen 41 C3151205
UMLS 71 C0268608 C3151205

Summaries for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

UniProtKB/Swiss-Prot : 73 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 megaloblastic anemia and transcobalamin ii deficiency, 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 ataxia and global developmental delay

OMIM : 56 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)

KEGG : 36 Dihydrofolate reductase (DHFR) deficiency is a recessive inborn error of metabolism characterized by megaloblastic anemia and cerebral folate deficiency, with variable neurological findings. It is caused by mutations in the DHFR gene.

Wikipedia : 74 Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid,... more...

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 11)
# Related Disease Score Top Affiliating Genes
1 megaloblastic anemia 10.3
2 transcobalamin ii deficiency 10.2
3 neurodegeneration due to cerebral folate transport deficiency 10.2
4 deficiency anemia 10.2
5 alzheimer disease 10.0
6 parkinson disease, late-onset 10.0
7 homocystinuria-megaloblastic anemia, cble complementation type 10.0
8 pancytopenia 10.0
9 childhood absence epilepsy 10.0
10 tetrahydrobiopterin deficiency 10.0
11 homocystinuria without methylmalonic aciduria 10.0

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

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

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 global developmental delay 31 HP:0001263
3 hepatomegaly 31 HP:0002240
4 feeding difficulties 31 HP:0011968
5 pancytopenia 31 HP:0001876
6 pallor 31 HP:0000980
7 generalized hypotonia 31 HP:0001290
8 thrombocytopenia 31 HP:0001873
9 jaundice 31 HP:0000952
10 cerebellar hypoplasia 31 HP:0001321
11 absence seizure 31 HP:0002121
12 poor head control 31 HP:0002421
13 delayed myelination 31 HP:0012448
14 cerebral atrophy 31 HP:0002059
15 postnatal microcephaly 31 HP:0005484
16 megaloblastic anemia 31 HP:0001889
17 eyelid myoclonus 31 HP:0025097

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
ataxia
poor head control
delayed myelination
cerebral atrophy
absence seizures
more
Hematology:
pancytopenia
thrombocytopenia
megaloblastic anemia
hypersegmented neutrophils

Head And Neck Eyes:
icterus
eyelid myoclonus

Growth Other:
poor feeding

Head And Neck Head:
microcephaly, acquired

Abdomen Liver:
hepatomegaly

Skin Nails Hair Skin:
pallor

Muscle Soft Tissue:
hypotonia

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

Clinical features from OMIM:

613839

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:

40
Neutrophil

Publications for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

Articles related to Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency:

# Title Authors PMID Year
1
Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. 6 61 56
21310277 2011
2
Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency. 61 56 6
21310276 2011
3
Hereditary abnormal transcobalamin II previously diagnosed as congenital dihydrofolate reductase deficiency. 56
6700662 1984
4
Dihydrofolate reductase deficiency causing megaloblastic anemia in two families. 56
1060915 1976
5
Inborn errors of folate metabolism (first of two parts). 56
1099447 1975
6
Knockout of dihydrofolate reductase in mice induces hypertension and abdominal aortic aneurysm via mitochondrial dysfunction. 61
30954686 2019
7
Supplementation of serum free media with HT is not sufficient to restore growth properties of DHFR-/- cells in fed-batch processes - Implications for designing novel CHO-based expression platforms. 61
21345355 2011
8
Identification of Cryptosporidium parvum dihydrofolate reductase inhibitors by complementation in Saccharomyces cerevisiae. 61
10722506 2000
9
Expression and amplification of engineered mouse dihydrofolate reductase minigenes. 61
6835212 1983

Variations for Megaloblastic Anemia Due to Dihydrofolate Reductase Deficiency

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

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DHFR NM_000791.4(DHFR):c.238C>T (p.Leu80Phe)SNV Pathogenic 29673 rs387906619 5:79945212-79945212 5:80649393-80649393
2 DHFR NM_000791.4(DHFR):c.458A>T (p.Asp153Val)SNV Pathogenic 29674 rs121913223 5:79929723-79929723 5:80633904-80633904

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

73
# Symbol AA change Variation ID SNP ID
1 DHFR p.Leu80Phe VAR_065818 rs387906619
2 DHFR p.Asp153Val VAR_065819 rs121913223

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:

36
# 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 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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