CIMAH
MCID: CMB083
MIFTS: 23

Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia (CIMAH)

Categories: Genetic diseases, Immune diseases, Mental diseases, Metabolic diseases, Neuronal diseases

Aliases & Classifications for Combined Immunodeficiency and Megaloblastic Anemia with or...

MalaCards integrated aliases for Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia:

Name: Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia 57 74 6
Cimah 57 74
Methylenetetrahydrofolate Dehydrogenase 1 Deficiency 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable clinical presentation
patients respond to folinic acid supplementation


HPO:

32
combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 617780
MeSH 44 D008661

Summaries for Combined Immunodeficiency and Megaloblastic Anemia with or...

OMIM : 57 Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia is an inborn error of folate metabolism due to deficiency of methylenetetrahydrofolate dehydrogenase-1. Manifestations may include hemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild mental retardation, lymphopenia involving all subsets, and low T-cell receptor excision circles. Folinic acid supplementation is an effective treatment (summary by Ramakrishnan et al., 2016). (617780)

MalaCards based summary : Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia, is also known as cimah. An important gene associated with Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia is MTHFD1 (Methylenetetrahydrofolate Dehydrogenase, Cyclohydrolase And Formyltetrahydrofolate Synthetase 1). Affiliated tissues include t cells, liver and b cells, and related phenotypes are autoimmunity and seizures

UniProtKB/Swiss-Prot : 74 Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia: An autosomal recessive disorder due to an inborn error of folate metabolism. Variable clinical manifestations include hemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild mental retardation, and lymphopenia.

Related Diseases for Combined Immunodeficiency and Megaloblastic Anemia with or...

Symptoms & Phenotypes for Combined Immunodeficiency and Megaloblastic Anemia with or...

Human phenotypes related to Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 autoimmunity 32 very rare (1%) HP:0002960
2 seizures 32 HP:0001250
3 hearing impairment 32 HP:0000365
4 intellectual disability, mild 32 HP:0001256
5 vomiting 32 HP:0002013
6 pancytopenia 32 HP:0001876
7 decreased antibody level in blood 32 HP:0004313
8 lymphopenia 32 HP:0001888
9 thrombocytosis 32 HP:0001894
10 recurrent pneumonia 32 HP:0006532
11 eczema 32 HP:0000964
12 asthenia 32 HP:0025406
13 severe combined immunodeficiency 32 HP:0004430
14 megaloblastic anemia 32 HP:0001889
15 decreased methylcobalamin 32 HP:0003223
16 septic arthritis 32 HP:0003095

Symptoms via clinical synopsis from OMIM:

57
Abdomen Gastrointestinal:
vomiting

Immunology:
recurrent infections
hypogammaglobulinemia
autoimmune disease (in some patients)
low nk cells
low t cells
more
Neurologic Behavioral Psychiatric Manifestations:
asthenia

Skeletal:
septic arthritis

Abdomen Liver:
liver fibrosis

Head And Neck Ears:
hearing loss, mild (in 1 patient)

Genitourinary Kidneys:
atypical hemolytic uremic syndrome

Hematology:
pancytopenia
lymphopenia
thrombocytosis
macrocytic anemia
megaloblastic anemia
more
Skin Nails Hair Skin:
eczema

Laboratory Abnormalities:
decreased methylcobalamin
normal serum cobalamin

Respiratory:
recurrent pulmonary infections

Neurologic Central Nervous System:
seizures (in 1 patient)
mental retardation, mild (in 1 patient)

Genitourinary External Genitalia Female:
moniliasis

Metabolic Features:
hyperhomocysteinemia (in some patients)

Clinical features from OMIM:

617780

Drugs & Therapeutics for Combined Immunodeficiency and Megaloblastic Anemia with or...

Search Clinical Trials , NIH Clinical Center for Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia

Genetic Tests for Combined Immunodeficiency and Megaloblastic Anemia with or...

Anatomical Context for Combined Immunodeficiency and Megaloblastic Anemia with or...

MalaCards organs/tissues related to Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia:

41
T Cells, Liver, B Cells, Nk Cells

Publications for Combined Immunodeficiency and Megaloblastic Anemia with or...

Articles related to Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia:

# Title Authors PMID Year
1
Precision Molecular Diagnosis Defines Specific Therapy in Combined Immunodeficiency with Megaloblastic Anemia Secondary to MTHFD1 Deficiency. 8 71
27707659 2016
2
Characterization and review of MTHFD1 deficiency: four new patients, cellular delineation and response to folic and folinic acid treatment. 8 71
25633902 2015
3
Novel inborn error of folate metabolism: identification by exome capture and sequencing of mutations in the MTHFD1 gene in a single proband. 8 71
21813566 2011
4
Severe combined immunodeficiency resulting from mutations in MTHFD1. 8
23296427 2013
5
Channeling efficiency in the bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase domain: the effects of site-directed mutagenesis of NADP binding residues. 71
11004530 2000

Variations for Combined Immunodeficiency and Megaloblastic Anemia with or...

ClinVar genetic disease variations for Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 MTHFD1 NM_005956.4(MTHFD1): c.727+1G> A single nucleotide variant Pathogenic rs781065280 14:64886644-64886644 14:64419926-64419926
2 MTHFD1 NM_005956.4(MTHFD1): c.1674G> A (p.Thr558=) single nucleotide variant Pathogenic rs1456143398 14:64905890-64905890 14:64439172-64439172
3 MTHFD1 NM_005956.4(MTHFD1): c.673G> T (p.Glu225Ter) single nucleotide variant Pathogenic rs760889414 14:64886589-64886589 14:64419871-64419871
4 MTHFD1 NG_012450.1: g.(45534_?)_(?_47555)del deletion Pathogenic
5 MTHFD1 NM_005956.4(MTHFD1): c.152T> C (p.Leu51Pro) single nucleotide variant Likely pathogenic rs1555336810 14:64877833-64877833 14:64411115-64411115
6 MTHFD1 NM_005956.4(MTHFD1): c.146C> T (p.Ser49Phe) single nucleotide variant Likely pathogenic rs370444838 14:64877827-64877827 14:64411109-64411109
7 MTHFD1 NM_005956.4(MTHFD1): c.517C> T (p.Arg173Cys) single nucleotide variant Likely pathogenic rs141210410 14:64884644-64884644 14:64417926-64417926
8 MTHFD1 NM_005956.4(MTHFD1): c.806C> T (p.Thr269Ile) single nucleotide variant Likely pathogenic rs1555337681 14:64891600-64891600 14:64424882-64424882

UniProtKB/Swiss-Prot genetic disease variations for Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia:

74
# Symbol AA change Variation ID SNP ID
1 MTHFD1 p.Ser49Phe VAR_074075 rs370444838
2 MTHFD1 p.Arg173Cys VAR_074076 rs141210410
3 MTHFD1 p.Thr269Ile VAR_074077 rs155533768
4 MTHFD1 p.Leu51Pro VAR_080873 rs155533681

Expression for Combined Immunodeficiency and Megaloblastic Anemia with or...

Search GEO for disease gene expression data for Combined Immunodeficiency and Megaloblastic Anemia with or Without Hyperhomocysteinemia.

Pathways for Combined Immunodeficiency and Megaloblastic Anemia with or...

GO Terms for Combined Immunodeficiency and Megaloblastic Anemia with or...

Sources for Combined Immunodeficiency and Megaloblastic Anemia with or...

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54 NINDS
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58 OMIM via Orphanet
62 PubMed
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69 SNOMED-CT via HPO
70 TGDB
71 Tocris
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73 UMLS via Orphanet
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