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Constitutional megaloblastic anemia with severe neurologic disease

MedGen UID:
462555
Concept ID:
C3151205
Disease or Syndrome
Synonyms: DHFR DEFICIENCY; Megaloblastic anemia due to dihydrofolate reductase deficiency
SNOMED CT: Megaloblastic anemia due to dihydrofolate reductase deficiency (866092006)
 
Gene (location): DHFR (5q14.1)
 
Monarch Initiative: MONDO:0013456
OMIM®: 613839
Orphanet: ORPHA319651

Definition

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 epilepsy with learning difficulties to lack of symptoms (Cario et al., 2011). Treatment with folinic acid can ameliorate some of the symptoms. [from OMIM]

Clinical features

From HPO
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Absence seizure with eyelid myoclonia
MedGen UID:
581541
Concept ID:
C0393722
Disease or Syndrome
An absence with eyelid myoclonia seizure is a type of generalized non-motor (absence) seizure characterised by forced upward jerking of the eyelids during an absence seizure.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Eyelid myoclonus
MedGen UID:
148288
Concept ID:
C0751349
Disease or Syndrome
Marked, involuntary jerking of the eyelids.
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
Decreased CSF 5-methyltetrahydrofolate concentration
MedGen UID:
893131
Concept ID:
C4022901
Finding
A reduced concentration of 5-methyltetrahydrofolate(2-) in the cerebrospinal fluid (CSF). 5-methyltetrahydrofolate is the active folate metabolite.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterised by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
Megaloblastic anemia
MedGen UID:
1527
Concept ID:
C0002888
Disease or Syndrome
Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts).
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Increased mean corpuscular volume
MedGen UID:
81303
Concept ID:
C0302845
Finding
Larger than normal size of erythrocytes.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Secondary microcephaly
MedGen UID:
608952
Concept ID:
C0431352
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Abnormal blood folate concentration
MedGen UID:
866690
Concept ID:
C4021037
Finding
Any deviation from the normal concentration of folate in the blood circulation.
Increased circulating lactate dehydrogenase concentration
MedGen UID:
1377250
Concept ID:
C4477095
Finding
An elevated level of the enzyme lactate dehydrogenase in the blood circulation.
Pallor
MedGen UID:
10547
Concept ID:
C0030232
Finding
Abnormally pale skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVConstitutional megaloblastic anemia with severe neurologic disease
Follow this link to review classifications for Constitutional megaloblastic anemia with severe neurologic disease in Orphanet.

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