Homocystinuria due to methylene tetrahydrofolate reductase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: MTHFR DEFICIENCY MTHFR DEFICIENCY, THERMOLABILE TYPE, INCLUDED
METHYLENETETRAHYDROFOLATE REDUCTASE DEFICIENCY
MTHFR deficiency
Methylene tetrahydrofolate reductase deficiency
Number of Symptoms 14
OrphanetNr: 395
OMIM Id: 236250
ICD-10: E72.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of folate metabolism and transport
 -Rare genetic disease
Rare hereditary metabolic disease with peripheral neuropathy
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0002156) Homocystinuria 12 / 7739
2
(HPO:0000252) Microcephaly 832 / 7739
3
(HPO:0000708) Behavioral abnormality 212 / 7739
4
(HPO:0001288) Gait disturbance 318 / 7739
5
(HPO:0001250) Seizures 1245 / 7739
6
(HPO:0001263) Global developmental delay 853 / 7739
7
(HPO:0003401) Paresthesia 42 / 7739
8
(HPO:0002311) Incoordination 84 / 7739
9
(HPO:0001297) Stroke 44 / 7739
10
(HPO:0002160) Hyperhomocystinemia 10 / 7739
11
(HPO:0001324) Muscle weakness 859 / 7739
12
(OMIM) Low to normal plasma methionine 1 / 7739
13
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739
14
(MedDRA:10070309) Methylenetetrahydrofolate reductase deficiency 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Methylenetetrahydrofolate reductase deficiency is a common inborn error of folate metabolism. The phenotypic spectrum ranges from severe neurologic deterioration and early death to asymptomatic adults. In the classic form, both thermostable and thermolabile enzyme variants have been identified ...
Diagnosis OMIM - Prenatal Diagnosis

Christensen and Brandt (1985) made a prenatal diagnosis of MTHFR deficiency.
Clinical Description OMIM Freeman et al. (1972) studied a 15-year-old mildly retarded black female with a 2-year history of progressive withdrawal, hallucinations, delusions, and catatonia unresponsive to psychotherapy. Homocystinuria without elevation of plasma methionine was found. Psychotic symptoms gradually disappeared with ...
Genotype-Phenotype Correlations OMIM - Coronary Artery Disease

Morita et al. (1997) studied 362 Japanese male patients with angiographically confirmed coronary artery disease and 778 controls. They reported a significantly higher frequency of the 677C-T allele (607093.0003) in the disease ...

Molecular genetics OMIM By RT-PCR of RNA from MTHFR-deficient patients, followed by single-strand conformation polymorphism (SSCP) analysis, Goyette et al. (1994) identified 3 substitutions in the MTHFR gene: 2 missense mutations (in residues conserved in the enzyme and bacteria) and 1 ...