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Developmental and epileptic encephalopathy, 50(DEE50)

MedGen UID:
904125
Concept ID:
C4225320
Disease or Syndrome
Synonyms: DEE50; Epileptic encephalopathy, early infantile, 50
SNOMED CT: Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase congenital disorder of glycosylation (1237417007); CAD-CDG - carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase congenital disorder of glycosylation (1237417007); Carbohydrate deficient glycoprotein syndrome type Iz (1237417007); Congenital disorder of glycosylation type 1z (1237417007)
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).
 
Gene (location): CAD (2p23.3)
 
Monarch Initiative: MONDO:0014647
OMIM®: 616457
Orphanet: ORPHA448010

Definition

Developmental and epileptic encephalopathy-50 (DEE50) is an autosomal recessive progressive neurodegenerative neurometabolic disorder characterized by delayed psychomotor development, early-onset refractory seizures, severe developmental regression, and normocytic anemia. Onset is within the first months or years of life. Evidence suggests that affected children can have a favorable response to treatment with uridine (summary by Koch et al., 2017). For a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Clinical features

From HPO
Oroticaciduria
MedGen UID:
78642
Concept ID:
C0268128
Finding
An increased concentration of orotic acid in the urine.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Global brain atrophy
MedGen UID:
66840
Concept ID:
C0241816
Pathologic Function
Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size.
Epileptic encephalopathy
MedGen UID:
452596
Concept ID:
C0543888
Disease or Syndrome
A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death.
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.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Poor speech
MedGen UID:
341172
Concept ID:
C1848207
Finding
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Schistocytosis
MedGen UID:
576247
Concept ID:
C0344386
Laboratory or Test Result
The presence of an abnormal number of fragmented red blood cells (schistocytes) in the blood.
Acanthocytosis
MedGen UID:
195801
Concept ID:
C0687751
Disease or Syndrome
Acanthocytosis is a type of poikilocytosis characterized by the presence of spikes on the cell surface. The cells have an irregular shape resembling many-pointed stars.
Anisopoikilocytosis
MedGen UID:
436556
Concept ID:
C2675920
Finding
A type of poikilocytosis characterized by the presence in the blood of erythrocytes of varying sizes and abnormal shapes.
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.
Renal tubular acidosis
MedGen UID:
90
Concept ID:
C0001126
Disease or Syndrome
Acidosis owing to malfunction of the kidney tubules with accumulation of metabolic acids and hyperchloremia, potentially leading to complications including hypokalemia, hypercalcinuria, nephrolithiasis and nephrocalcinosis.
Abnormal glycosylation
MedGen UID:
868547
Concept ID:
C4022946
Finding
An anomaly of a glycosylation process, i.e., a process involved in the covalent attachment of a glycosyl residue to a substrate molecule.
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDevelopmental and epileptic encephalopathy, 50

Professional guidelines

PubMed

Lattanzi S, Trinka E, Striano P, Rocchi C, Salvemini S, Silvestrini M, Brigo F
CNS Drugs 2021 Mar;35(3):265-281. Epub 2021 Mar 22 doi: 10.1007/s40263-021-00807-y. PMID: 33754312Free PMC Article
Strzelczyk A, Schubert-Bast S
CNS Drugs 2021 Jan;35(1):61-83. Epub 2021 Jan 21 doi: 10.1007/s40263-020-00784-8. PMID: 33479851Free PMC Article
Hebbar M, Mefford HC
F1000Res 2020;9 Epub 2020 Mar 12 doi: 10.12688/f1000research.21366.1. PMID: 32201576Free PMC Article

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