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Glutamate formiminotransferase deficiency

MedGen UID:: 82823
•Concept ID:: C0268609
•: Disease or Syndrome

Synonyms:	Arakawa syndrome 1; Formiminoglutamic acidemia; Formiminoglutamic aciduria; Formiminoglutamicaciduria (FIGLU-uria); Formiminotransferase Deficiency; Formiminotransferase deficiency syndrome
SNOMED CT:	Deficiency of glutamate formiminotransferase (59761008); Deficiency of glutamate formyltransferase (59761008); Glutamate formiminotransferase deficiency (59761008); FIGLUria (59761008); Formiminoglutamic aciduria (59761008)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	FTCD (21q22.3)

Monarch Initiative:	MONDO:0009240
OMIM®:	229100
Orphanet:	ORPHA51208

Definition

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). [from OMIM]

Additional description

From MedlinePlus Genetics
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. https://medlineplus.gov/genetics/condition/glutamate-formiminotransferase-deficiency

Clinical features

From HPO

Aminoaciduria

MedGen UID:: 116067
•Concept ID:: C0238621
•: Disease or Syndrome

An increased concentration of an amino acid in the urine.

See: Feature record | Search on this feature

Elevated urinary formiminoglutamic acid level

MedGen UID:: 1841630
•Concept ID:: C5826631
•: Finding

The concentration of formiminoglutamic acid in the urine, normalized for urine concentration, is above the upper limit of normal.

See: Feature record | Search on this feature

Growth delay

MedGen UID:: 99124
•Concept ID:: C0456070
•: Pathologic Function

A deficiency or slowing down of growth pre- and postnatally.

See: Feature record | Search on this feature

Intellectual disability

MedGen UID:: 811461
•Concept ID:: C3714756
•: Mental or Behavioral Dysfunction

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

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Megaloblastic anemia

MedGen UID:: 1527
•Concept ID:: C0002888
•: Disease or Syndrome

Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts).

See: Feature record | Search on this feature

Hypersegmentation of neutrophil nuclei

MedGen UID:: 870828
•Concept ID:: C4025288
•: Finding

An excessive division of the lobes of the nucleus of a neutrophil.

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Positive ferric chloride test

MedGen UID:: 871120
•Concept ID:: C4025589
•: Finding

If positive, the ferric chloride test indicates an increased concentration of phenols in the urine or blood.

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Abnormality of blood and blood-forming tissues
- Megaloblastic anemia
Abnormality of metabolism/homeostasis
- Positive ferric chloride test
Abnormality of the genitourinary system
- Aminoaciduria
- Elevated urinary formiminoglutamic acid level
Abnormality of the immune system
- Hypersegmentation of neutrophil nuclei
Abnormality of the nervous system
- Intellectual disability
Growth abnormality
- Growth delay

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVGlutamate formiminotransferase deficiency

Constitutional megaloblastic anemia due to folate metabolism disorder
- Glutamate formiminotransferase deficiency

Follow this link to review classifications for Glutamate formiminotransferase deficiency in Orphanet.

Recent clinical studies

Diagnosis

An Unusual Peak in a Common Clinical Presentation.

Sudrié-Arnaud B, Snanoudj S, Imbard A, Dabaj I, Tebani A
Clin Chem 2021 Apr 29;67(5):799-801. doi: 10.1093/clinchem/hvab012. PMID: 33928370

Allelic spectrum of formiminotransferase-cyclodeaminase gene variants in individuals with formiminoglutamic aciduria.

Majumdar R, Yori A, Rush PW, Raymond K, Gavrilov D, Tortorelli S, Matern D, Rinaldo P, Feldman GL, Oglesbee D
Mol Genet Genomic Med 2017 Nov;5(6):795-799. Epub 2017 Sep 11 doi: 10.1002/mgg3.333. PMID: 29178637 Free PMC Article

Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate formiminotransferase deficiency.

Solans A, Estivill X, de la Luna S
Cytogenet Cell Genet 2000;88(1-2):43-9. doi: 10.1159/000015483. PMID: 10773664

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