Congenital brain dysgenesis due to glutamine synthetase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: GLUTAMINE SYNTHASE DEFICIENCY, CONGENITAL SYSTEMIC
Inherited glutamine synthetase deficiency
Inherited GS deficiency
Number of Symptoms 38
OrphanetNr: 71278
OMIM Id: 610015
ICD-10: E72.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 2 cases [Orphanet]
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of glutamine metabolism
 -Rare genetic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0005280) Depressed nasal bridge 381 / 7739
2
 (HPO:0000431) Wide nasal bridge 290 / 7739
3
 (HPO:0000369) Low-set ears 372 / 7739
4
 (HPO:0001298) Encephalopathy 72 / 7739
5
 (HPO:0001250) Seizures 1245 / 7739
6
 (HPO:0001347) Hyperreflexia 363 / 7739
7
 (HPO:0011344) Severe global developmental delay 46 / 7739
8
 (HPO:0009829) Phocomelia 20 / 7739
9
 (HPO:0001371) Flexion contracture rare [HPO:skoehler] 220 / 7739
10
 (HPO:0005011) Mesomelic arm shortening 13 / 7739
11
 (HPO:0003027) Mesomelia 58 / 7739
12
 (HPO:0002983) Micromelia rare [HPO:skoehler] 130 / 7739
13
 (HPO:0009827) Amelia 12 / 7739
14
 (HPO:0000988) Skin rash 98 / 7739
15
 (HPO:0001662) Bradycardia 41 / 7739
16
 (HPO:0001987) Hyperammonemia 50 / 7739
17
 (HPO:0002104) Apnea 106 / 7739
18
 (HPO:0002093) Respiratory insufficiency 410 / 7739
19
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
20
 (HPO:0001324) Muscle weakness 859 / 7739
21
 (HPO:0010547) Muscle flaccidity 466 / 7739
22
 (HPO:0001252) Muscular hypotonia 990 / 7739
23
 (OMIM) Blistering erythematous rash 1 / 7739
24
 (OMIM) Delayed development, severe 2 / 7739
25
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
26
 (HPO:0012444) Brain atrophy 24 / 7739
27
 (OMIM) Decreased glutamine in bodily fluids 1 / 7739
28
 (HPO:0002119) Ventriculomegaly 253 / 7739
29
 (OMIM) Attenuated gyri 1 / 7739
30
 (OMIM) Necrotic epidermolysis 1 / 7739
31
 (HPO:0002416) Subependymal cysts 6 / 7739
32
 (OMIM) Abnormal gyri 3 / 7739
33
 (HPO:0001522) Death in infancy occasional [HPO:skoehler] 275 / 7739
34
 (HPO:0003429) CNS hypomyelination 21 / 7739
35
 (OMIM) Small, smooth cerebellum 1 / 7739
36
 (HPO:0007109) Periventricular cysts 4 / 7739
37
 (OMIM) Broad, flat nasal root 4 / 7739
38
 (HPO:0002079) Hypoplasia of the corpus callosum 161 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Congenital glutamine deficiency is a severe autosomal recessive disorder characterized by onset at birth of encephalopathy, lack of normal development, seizures, and hypotonia associated with variable brain abnormalities. Three patients have been reported (summary by Haberle et al., ...
Clinical Description OMIM Haberle et al. (2005) described 2 presumably unrelated newborns of consanguineous Turkish ancestry who had congenital glutamine synthetase deficiency with severe brain malformations resulting in multiorgan failure and neonatal death. Glutamine was largely absent from their serum, urine, ...
Molecular genetics OMIM Haberle et al. (2005) detected homozygous mutations in the GLUL gene (138290) in each of 2 Turkish patients with a systemic glutamine deficiency. One patient carried an arg324-to-cys substitution (R324C; 138290.0001), and the other an arg341-to-cys substitution (R341C; ...