Constitutional megaloblastic anemia with severe neurologic disease

General Information (adopted from Orphanet):

Synonyms, Signs: Dihydrofolate reductase deficiency
dhfr deficiency
Number of Symptoms 29
OrphanetNr: 319651
OMIM Id: 613839
ICD-10: D52.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Constitutional megaloblastic anemia due to folate metabolism disorder
 -Rare genetic disease
 -Rare hematologic disease
Disorder of folate metabolism and transport
 -Rare genetic disease
Other metabolic disease with epilepsy
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0005484) Postnatal microcephaly 32 / 7739
2
 (HPO:0002121) Absence seizures 62 / 7739
3
 (HPO:0001251) Ataxia 413 / 7739
4
 (HPO:0001263) Global developmental delay 853 / 7739
5
 (HPO:0001328) Specific learning disability 114 / 7739
6
 (HPO:0000952) Jaundice 105 / 7739
7
 (HPO:0002240) Hepatomegaly 467 / 7739
8
 (HPO:0011968) Feeding difficulties 240 / 7739
9
 (HPO:0000980) Pallor 52 / 7739
10
 (HPO:0001876) Pancytopenia 89 / 7739
11
 (HPO:0001873) Thrombocytopenia 224 / 7739
12
 (HPO:0001889) Megaloblastic anemia 28 / 7739
13
 (HPO:0002421) Poor head control 23 / 7739
14
 (HPO:0001324) Muscle weakness 859 / 7739
15
 (HPO:0001252) Muscular hypotonia 990 / 7739
16
 (HPO:0010547) Muscle flaccidity 466 / 7739
17
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
18
 (HPO:0003828) Variable expressivity 130 / 7739
19
 (HPO:0007360) Aplasia/Hypoplasia of the cerebellum 10 / 7739
20
 (HPO:0012448) Delayed myelination 51 / 7739
21
 (OMIM) Normal serum folate 2 / 7739
22
 (OMIM) Neuronal and vascular calcifications 1 / 7739
23
 (HPO:0002059) Cerebral atrophy 171 / 7739
24
 (OMIM) Decreased CSF tetrahydrofolate and 5-methyltetrahydrofolate 1 / 7739
25
 (OMIM) Eyelid myoclonus 1 / 7739
26
 (OMIM) Refractory seizures 15 / 7739
27
 (OMIM) Hypersegmented neutrophils 1 / 7739
28
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
29
 (OMIM) Decreased activity of dihydrofolate reductase 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Banka et al. (2011) reported a boy, born of first-cousin British Pakistani parents, who presented at age 4 months with megaloblastic anemia and acquired microcephaly. He showed poor feeding, pallor, and soon developed pancytopenia and refractory seizures. Brain ...
Molecular genetics OMIM In 6 patients with megaloblastic anemia and DHFR deficiency, Banka et al. (2011) and Cario et al. (2011) simultaneously and independently identified homozygous mutations in the DHFR gene (L80F; 126260.0001 and D153V; 126260.0002, respectively). The phenotypes were different: ...