FIGLU-URIA
MCID: GLT005
MIFTS: 42

Glutamate Formiminotransferase Deficiency (FIGLU-URIA)

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

Aliases & Classifications for Glutamate Formiminotransferase Deficiency

MalaCards integrated aliases for Glutamate Formiminotransferase Deficiency:

Name: Glutamate Formiminotransferase Deficiency 57 12 20 43 58 72 29 13 54 6 44 15 39 70
Formiminoglutamic Aciduria 57 12 43 58 72
Formiminotransferase Deficiency 57 43 72 36
Arakawa Syndrome 1 12 20 43
Figlu-Uria 57 43 72
Formiminotransferase Cyclodeaminase Deficiency 12 58
Formiminotransferase Deficiency Syndrome 12 20
Formiminoglutamic Acidemia 12 20
Formiminoglutamicaciduria 20 72
Ftcd Deficiency 12 58
Figluria 12

Characteristics:

Orphanet epidemiological data:

58
formiminoglutamic aciduria
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
glutamate formiminotransferase deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism
Rare haematological diseases


External Ids:

Disease Ontology 12 DOID:0111679
OMIM® 57 229100
KEGG 36 H01262
MeSH 44 C537425
SNOMED-CT 67 59761008
ICD10 via Orphanet 33 E70.8
UMLS via Orphanet 71 C0268609
Orphanet 58 ORPHA51208
MedGen 41 C0268609
UMLS 70 C0268609

Summaries for Glutamate Formiminotransferase Deficiency

MedlinePlus Genetics : 43 Glutamate formiminotransferase deficiency is an inherited disorder that affects physical and mental development. There are two forms of this condition, which are distinguished by the severity of symptoms.People with the mild form of glutamate formiminotransferase deficiency have minor delays in physical and mental development and may have mild intellectual disability. They also have unusually high levels of a molecule called formiminoglutamate (FIGLU) in their urine.Individuals affected by the severe form of this disorder have profound intellectual disability and delayed development of motor skills such as sitting, standing, and walking. In addition to FIGLU in their urine, they have elevated amounts of certain B vitamins (called folates) in their blood.The severe form of glutamate formiminotransferase deficiency is also characterized by megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, and tingling or numbness in the hands and feet.

MalaCards based summary : Glutamate Formiminotransferase Deficiency, also known as formiminoglutamic aciduria, is related to homocystinuria and megaloblastic anemia. An important gene associated with Glutamate Formiminotransferase Deficiency is FTCD (Formimidoyltransferase Cyclodeaminase), and among its related pathways/superpathways are Histidine metabolism and One carbon pool by folate. Affiliated tissues include neutrophil and lung, and related phenotypes are intellectual disability and aminoaciduria

Disease Ontology : 12 A vitamin metabolic disorder characterized by elevated formiminoglutamate in urine and plasma and variable intellectual, developmental, and hematological phenotypes that has material basis in homozygous or compound heterozygous mutation in FTCD on chromosome 21q22.3.

GARD : 20 Glutamate formiminotransferase deficiency is an inherited metabolic disorder that affects physical and mental development. There are two forms of this condition, a mild form and a severe form. People with the mild form have minor delays in physical and mental development and may have mild intellectual disability. They also have unusually high levels of a molecule called formiminoglutamate (FIGLU) in their urine. Individuals with the severe form have profound intellectual disability, delayed development of motor skills (sitting, standing, and walking) and megaloblastic anemia. In addition to FIGLU in their urine, they have elevated amounts of certain B vitamins (called folates) in their blood. Glutamate formiminotransferase deficiency is caused by mutations in the FTCD gene. It is inherited in an autosomal recessive pattern. There are currently no treatments known to prevent or delay the signs and symptoms of glutamate formiminotransferase deficiency.

OMIM® : 57 Glutamate formiminotransferase deficiency is an autosomal recessive disorder and the second most common inborn error of folate metabolism. Features of a severe phenotype include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematologic abnormalities (summary by Hilton et al., 2003). (229100) (Updated 05-Apr-2021)

KEGG : 36 Formiminotransferase deficiency is an autosomal recessive disorder of folate metabolism. It is due to defects in the bifunctional enzyme glutamate formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype include megaloblastic anemia and mental retardation. Features of a mild phenotype include mild developmental delay and no hematological abnormalities.

UniProtKB/Swiss-Prot : 72 Glutamate formiminotransferase deficiency: Autosomal recessive disorder. Features of a severe phenotype, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities.

Related Diseases for Glutamate Formiminotransferase Deficiency

Graphical network of the top 20 diseases related to Glutamate Formiminotransferase Deficiency:



Diseases related to Glutamate Formiminotransferase Deficiency

Symptoms & Phenotypes for Glutamate Formiminotransferase Deficiency

Human phenotypes related to Glutamate Formiminotransferase Deficiency:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 aminoaciduria 31 HP:0003355
3 growth delay 31 HP:0001510
4 megaloblastic anemia 31 HP:0001889
5 hypersegmentation of neutrophil nuclei 31 HP:0004821
6 positive ferric chloride test 31 HP:0003612

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Heme:
megaloblastic anemia

Neuro:
mental deficiency

Lab:
hypersegmentation of neutrophil nuclei
positive ferric chloride test
formiminoglutamic aciduria
glutamate formiminotransferase deficiency
hyperfolicacidemia

Growth:
physical retardation

Clinical features from OMIM®:

229100 (Updated 05-Apr-2021)

Drugs & Therapeutics for Glutamate Formiminotransferase Deficiency

Search Clinical Trials , NIH Clinical Center for Glutamate Formiminotransferase Deficiency

Cochrane evidence based reviews: glutamate formiminotransferase deficiency

Genetic Tests for Glutamate Formiminotransferase Deficiency

Genetic tests related to Glutamate Formiminotransferase Deficiency:

# Genetic test Affiliating Genes
1 Glutamate Formiminotransferase Deficiency 29 FTCD

Anatomical Context for Glutamate Formiminotransferase Deficiency

MalaCards organs/tissues related to Glutamate Formiminotransferase Deficiency:

40
Neutrophil, Lung

Publications for Glutamate Formiminotransferase Deficiency

Articles related to Glutamate Formiminotransferase Deficiency:

(show all 22)
# Title Authors PMID Year
1
The molecular basis of glutamate formiminotransferase deficiency. 54 61 57 6
12815595 2003
2
Allelic spectrum of formiminotransferase-cyclodeaminase gene variants in individuals with formiminoglutamic aciduria. 6 57 61
29178637 2017
3
A case of formiminoglutamic aciduria. Clinical and biochemical studies. 61 57
7262105 1981
4
Hydantoin-5-propionic aciduria in folic acid nondependent formiminoglutamic aciduria observed in two siblings. 57 61
1272625 1976
5
Metabolic studies of a family with massive formiminoglutamic aciduria. 61 57
235753 1975
6
Folic acid non-dependent formiminoglutamic aciduria in two siblings. 61 57
4413489 1974
7
Molecular diagnostic experience of whole-exome sequencing in adult patients. 6
26633545 2016
8
Inborn errors of folate metabolism (first of two parts). 57
1099447 1975
9
Defect of incorporation of glycine-1- 14 C into urinary uric acid in formiminotransferase deficiency syndrome. 57
5038586 1972
10
Familial occurrence of formiminotransferase deficiency of syndrome. 57
5305027 1968
11
Formiminotransferase deficiency syndrome associated with megaloblastic anemia responsive to pyridoxine or folic acid. 57
5301410 1968
12
Erythrocyte formiminotransferase activity in formiminotransferase deficiency syndrome. 57
5956503 1966
13
Formiminotransferase-deficiency syndrome: a new inborn error of folic acid metabolism. 57
5897668 1965
14
Falsely elevated C4-carnitine as expression of glutamate formiminotransferase deficiency in tandem mass spectrometry newborn screening. 61 54
16421867 2006
15
Structure of the bifunctional and Golgi-associated formiminotransferase cyclodeaminase octamer. 54 61
15272307 2004
16
Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate formiminotransferase deficiency. 54 61
10773664 2000
17
Characteristics and outcomes of patients with formiminoglutamic aciduria detected through newborn screening. 61
30740726 2019
18
Update and new concepts in vitamin responsive disorders of folate transport and metabolism. 61
22108709 2012
19
[Glutamate-formiminotransferase deficiency]. 61
9645043 1998
20
Orotic aciduria, homocystinuria, formiminoglutamic aciduria and megaloblastosis associated with the formiminotransferase/cyclodeaminase deficiency. 61
3728187 1986
21
Formiminoglutamic aciduria in a slightly retarded boy with chronic obstructive lung disease. 61
6796776 1981
22
"HYPERFOLIC-ACIDEMIA WITH FORMIMINOGLUTAMIC-ACIDURIA FOLLOWING HISTIDINE LOADING". SUGGESTED FOR A CASE OF CONGENITAL DEFICIENCY IN FORMIMINOTRANSFERASE. 61
14067261 1963

Variations for Glutamate Formiminotransferase Deficiency

ClinVar genetic disease variations for Glutamate Formiminotransferase Deficiency:

6 (show top 50) (show all 78)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FTCD NM_206965.2(FTCD):c.896G>C (p.Arg299Pro) SNV Pathogenic 4018 rs119469015 GRCh37: 21:47570043-47570043
GRCh38: 21:46150129-46150129
2 FTCD NM_206965.2(FTCD):c.763C>T (p.Arg255Ter) SNV Pathogenic 632385 rs140217223 GRCh37: 21:47570313-47570313
GRCh38: 21:46150399-46150399
3 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.403C>T (p.Arg135Cys) SNV Pathogenic 4017 rs28941768 GRCh37: 21:47571859-47571859
GRCh38: 21:46151945-46151945
4 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.378C>G (p.Tyr126Ter) SNV Pathogenic 459967 rs374724805 GRCh37: 21:47571884-47571884
GRCh38: 21:46151970-46151970
5 FTCD NM_206965.2(FTCD):c.211C>T (p.Arg71Ter) SNV Pathogenic 488890 rs8133955 GRCh37: 21:47574090-47574090
GRCh38: 21:46154176-46154176
6 FTCD NM_206965.2(FTCD):c.1607T>A (p.Leu536Ter) SNV Pathogenic 194395 rs149266909 GRCh37: 21:47556920-47556920
GRCh38: 21:46137006-46137006
7 FTCD NM_206965.2(FTCD):c.750C>G (p.Tyr250Ter) SNV Pathogenic 1030123 GRCh37: 21:47570326-47570326
GRCh38: 21:46150412-46150412
8 FTCD NM_206965.2(FTCD):c.990dup (p.Pro331fs) Duplication Pathogenic/Likely pathogenic 4019 rs398124234 GRCh37: 21:47565839-47565840
GRCh38: 21:46145925-46145926
9 FTCD NM_206965.2(FTCD):c.1358C>T (p.Thr453Met) SNV Conflicting interpretations of pathogenicity 209155 rs200283734 GRCh37: 21:47558507-47558507
GRCh38: 21:46138593-46138593
10 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.476C>T (p.Ala159Val) SNV Uncertain significance 340435 rs200652518 GRCh37: 21:47571632-47571632
GRCh38: 21:46151718-46151718
11 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.425G>A (p.Arg142Gln) SNV Uncertain significance 529458 rs375990689 GRCh37: 21:47571837-47571837
GRCh38: 21:46151923-46151923
12 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.469G>A (p.Asp157Asn) SNV Uncertain significance 657170 rs532226691 GRCh37: 21:47571639-47571639
GRCh38: 21:46151725-46151725
13 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.521C>T (p.Thr174Met) SNV Uncertain significance 962891 GRCh37: 21:47571587-47571587
GRCh38: 21:46151673-46151673
14 FTCD NM_206965.2(FTCD):c.197C>T (p.Ala66Val) SNV Uncertain significance 502351 rs199867833 GRCh37: 21:47574104-47574104
GRCh38: 21:46154190-46154190
15 FTCD NM_206965.2(FTCD):c.1615C>T (p.Arg539Trp) SNV Uncertain significance 958004 GRCh37: 21:47556912-47556912
GRCh38: 21:46136998-46136998
16 FTCD NM_206965.2(FTCD):c.1273C>T (p.Leu425Phe) SNV Uncertain significance 971763 GRCh37: 21:47558825-47558825
GRCh38: 21:46138911-46138911
17 FTCD NM_206965.2(FTCD):c.1166C>G (p.Thr389Arg) SNV Uncertain significance 340424 rs545214029 GRCh37: 21:47565425-47565425
GRCh38: 21:46145511-46145511
18 FTCD NM_206965.2(FTCD):c.1015T>A (p.Ser339Thr) SNV Uncertain significance 577189 rs1195012799 GRCh37: 21:47565815-47565815
GRCh38: 21:46145901-46145901
19 FTCD NM_206965.2(FTCD):c.764_765GA[1] (p.Glu256fs) Microsatellite Uncertain significance 631885 rs1568979227 GRCh37: 21:47570309-47570310
GRCh38: 21:46150395-46150396
20 FTCD NM_206965.2(FTCD):c.*1C>T SNV Uncertain significance 340411 rs144773622 GRCh37: 21:47556900-47556900
GRCh38: 21:46136986-46136986
21 FTCD NM_006657.3(FTCD):c.*113C>T SNV Uncertain significance 340407 rs886057173 GRCh37: 21:47556298-47556298
GRCh38: 21:46136384-46136384
22 FTCD NM_206965.2(FTCD):c.1291del (p.Glu431fs) Deletion Uncertain significance 631883 rs775788856 GRCh37: 21:47558807-47558807
GRCh38: 21:46138893-46138893
23 FTCD NM_206965.2(FTCD):c.997del (p.Arg333fs) Deletion Uncertain significance 631884 rs1568974130 GRCh37: 21:47565833-47565833
GRCh38: 21:46145919-46145919
24 FTCD NM_206965.2(FTCD):c.1312G>A (p.Ala438Thr) SNV Uncertain significance 645399 rs1162672679 GRCh37: 21:47558553-47558553
GRCh38: 21:46138639-46138639
25 FTCD NM_206965.2(FTCD):c.857G>A (p.Cys286Tyr) SNV Uncertain significance 656937 rs372299678 GRCh37: 21:47570082-47570082
GRCh38: 21:46150168-46150168
26 FTCD NM_206965.2(FTCD):c.959G>A (p.Arg320Gln) SNV Uncertain significance 665224 rs77740289 GRCh37: 21:47566189-47566189
GRCh38: 21:46146275-46146275
27 FTCD NC_000021.9:g.(?_46136967)_(46155543_?)dup Duplication Uncertain significance 831105 GRCh37: 21:47556881-47575457
GRCh38:
28 FTCD NM_206965.2(FTCD):c.1539+4_1539+11del Deletion Uncertain significance 842677 GRCh37: 21:47557142-47557149
GRCh38: 21:46137228-46137235
29 FTCD NM_206965.2(FTCD):c.984G>C (p.Glu328Asp) SNV Uncertain significance 862049 GRCh37: 21:47565846-47565846
GRCh38: 21:46145932-46145932
30 FTCD NM_206965.2(FTCD):c.319T>C (p.Cys107Arg) SNV Uncertain significance 665719 rs377359525 GRCh37: 21:47572869-47572869
GRCh38: 21:46152955-46152955
31 COL6A2 , FTCD NM_206965.2(FTCD):c.1540-17_1540-16del Deletion Uncertain significance 340413 rs747091513 GRCh37: 21:47557003-47557004
GRCh38: 21:46137089-46137090
32 COL6A2 , FTCD NM_006657.3(FTCD):c.*15C>A SNV Uncertain significance 340410 rs114980528 GRCh37: 21:47556396-47556396
GRCh38: 21:46136482-46136482
33 COL6A2 , FTCD NM_006657.3(FTCD):c.*67C>T SNV Uncertain significance 340408 rs139773262 GRCh37: 21:47556344-47556344
GRCh38: 21:46136430-46136430
34 COL6A2 , FTCD NM_006657.3(FTCD):c.*127C>A SNV Uncertain significance 340405 rs538433909 GRCh37: 21:47556284-47556284
GRCh38: 21:46136370-46136370
35 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.532G>T (p.Ala178Ser) SNV Uncertain significance 998469 GRCh37: 21:47571576-47571576
GRCh38: 21:46151662-46151662
36 FTCD NM_206965.2(FTCD):c.161C>T (p.Pro54Leu) SNV Uncertain significance 1000243 GRCh37: 21:47574140-47574140
GRCh38: 21:46154226-46154226
37 FTCD NM_206965.2(FTCD):c.214C>T (p.Leu72Phe) SNV Uncertain significance 1003070 GRCh37: 21:47574087-47574087
GRCh38: 21:46154173-46154173
38 FTCD NM_206965.2(FTCD):c.1429C>T (p.Arg477Trp) SNV Uncertain significance 1005867 GRCh37: 21:47558436-47558436
GRCh38: 21:46138522-46138522
39 FTCD NM_206965.2(FTCD):c.1352C>T (p.Pro451Leu) SNV Uncertain significance 340418 rs376845160 GRCh37: 21:47558513-47558513
GRCh38: 21:46138599-46138599
40 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.439G>A (p.Glu147Lys) SNV Uncertain significance 459968 rs754659947 GRCh37: 21:47571823-47571823
GRCh38: 21:46151909-46151909
41 FTCD NM_206965.2(FTCD):c.1364C>T (p.Ala455Val) SNV Uncertain significance 666112 rs61735840 GRCh37: 21:47558501-47558501
GRCh38: 21:46138587-46138587
42 FTCD NM_206965.2(FTCD):c.774+4A>G SNV Uncertain significance 846678 GRCh37: 21:47570298-47570298
GRCh38: 21:46150384-46150384
43 FTCD NM_206965.2(FTCD):c.61G>A (p.Asp21Asn) SNV Uncertain significance 846913 GRCh37: 21:47574240-47574240
GRCh38: 21:46154326-46154326
44 FTCD-AS1 , FTCD NM_206965.2(FTCD):c.530G>A (p.Gly177Glu) SNV Uncertain significance 962892 GRCh37: 21:47571578-47571578
GRCh38: 21:46151664-46151664
45 FTCD NM_206965.2(FTCD):c.625G>A (p.Gly209Arg) SNV Uncertain significance 340431 rs367906516 GRCh37: 21:47571483-47571483
GRCh38: 21:46151569-46151569
46 FTCD NM_206965.2(FTCD):c.1016C>A (p.Ser339Tyr) SNV Uncertain significance 1021953 GRCh37: 21:47565814-47565814
GRCh38: 21:46145900-46145900
47 FTCD NM_206965.2(FTCD):c.35C>T (p.Ser12Leu) SNV Uncertain significance 529459 rs201753824 GRCh37: 21:47575403-47575403
GRCh38: 21:46155489-46155489
48 FTCD NM_206965.2(FTCD):c.862_864del (p.Lys288del) Deletion Uncertain significance 944780 GRCh37: 21:47570075-47570077
GRCh38: 21:46150161-46150163
49 FTCD NM_206965.2(FTCD):c.274C>T (p.Pro92Ser) SNV Uncertain significance 282695 rs749149640 GRCh37: 21:47572914-47572914
GRCh38: 21:46153000-46153000
50 FTCD NM_206965.2(FTCD):c.1366dup (p.Glu456fs) Duplication Uncertain significance 194078 rs777099958 GRCh37: 21:47558498-47558499
GRCh38: 21:46138584-46138585

UniProtKB/Swiss-Prot genetic disease variations for Glutamate Formiminotransferase Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 FTCD p.Arg135Cys VAR_015887 rs28941768
2 FTCD p.Arg299Pro VAR_015888 rs119469015

Expression for Glutamate Formiminotransferase Deficiency

Search GEO for disease gene expression data for Glutamate Formiminotransferase Deficiency.

Pathways for Glutamate Formiminotransferase Deficiency

Pathways related to Glutamate Formiminotransferase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Histidine metabolism hsa00340
2 One carbon pool by folate hsa00670

Pathways related to Glutamate Formiminotransferase Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.56 UROC1 NAGA MTR MTHFD1L MMAA LMBRD1
2
Show member pathways
12.06 MTR MTHFD1L MMAA LMBRD1
3
Show member pathways
11.59 MTR MTHFD1L FTCD
4
Show member pathways
11.37 MTR MMAA
5
Show member pathways
10.84 UROC1 FTCD
6 10.12 MTR MMAA LMBRD1
7 9.65 UROC1 FTCD

GO Terms for Glutamate Formiminotransferase Deficiency

Biological processes related to Glutamate Formiminotransferase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular metabolic process GO:0044237 9.43 MTR FTCD
2 tetrahydrofolate interconversion GO:0035999 9.4 MTHFD1L FTCD
3 histidine catabolic process GO:0006548 9.37 UROC1 FTCD
4 histidine metabolic process GO:0006547 9.32 UROC1 FTCD
5 histidine catabolic process to glutamate and formate GO:0019557 9.26 UROC1 FTCD
6 histidine catabolic process to glutamate and formamide GO:0019556 9.16 UROC1 FTCD
7 folic acid-containing compound metabolic process GO:0006760 8.96 MTHFD1L FTCD
8 cobalamin metabolic process GO:0009235 8.8 MTR MMAA LMBRD1

Molecular functions related to Glutamate Formiminotransferase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cobalamin binding GO:0031419 8.62 MTR LMBRD1

Sources for Glutamate Formiminotransferase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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