U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Congenital brain dysgenesis due to glutamine synthetase deficiency(GLND)

MedGen UID:
400638
Concept ID:
C1864910
Disease or Syndrome
Synonyms: GLND; Glutamine deficiency, congenital; GLUTAMINE SYNTHASE DEFICIENCY, CONGENITAL SYSTEMIC; Glutamine synthetase deficiency, congenital systemic
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): GLUL (1q25.3)
 
Monarch Initiative: MONDO:0012393
OMIM®: 610015
Orphanet: ORPHA71278

Definition

Congenital glutamine deficiency (GLND) 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 (summary by Haberle et al., 2011). [from OMIM]

Clinical features

From HPO
Micromelia
MedGen UID:
10031
Concept ID:
C0025995
Congenital Abnormality
The presence of abnormally small extremities.
Bradycardia
MedGen UID:
140901
Concept ID:
C0428977
Finding
A slower than normal heart rate (in adults, slower than 60 beats per minute).
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
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.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Subependymal cysts
MedGen UID:
318876
Concept ID:
C1833431
Anatomical Abnormality
Cerebral cysts, usually located in the wall of the caudate nucleus or in the caudothalamic groove. They are found in up to 5.2% of all neonates, using transfontanellar ultrasound in the first days of life.
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Lateral ventricle dilatation
MedGen UID:
383904
Concept ID:
C1856409
Pathologic Function
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Brain atrophy
MedGen UID:
1643639
Concept ID:
C4551584
Disease or Syndrome
Partial or complete wasting (loss) of brain tissue that was once present.
Decreased CSF glutamine concentration
MedGen UID:
1707750
Concept ID:
C5139583
Finding
Abnormally decreased levels of glutamine in cerebrospinal fluid.
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.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Hypoglutaminemia
MedGen UID:
1671003
Concept ID:
C4732901
Finding
Decreased amount of glutamine in the blood.
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital brain dysgenesis due to glutamine synthetase deficiency
Follow this link to review classifications for Congenital brain dysgenesis due to glutamine synthetase deficiency in Orphanet.

Recent clinical studies

Diagnosis

Chang MC, Staklinski SJ, Malut VR, Pierre GL, Kilberg MS, Merritt ME
Nutrients 2023 Apr 18;15(8) doi: 10.3390/nu15081938. PMID: 37111157Free PMC Article

Therapy

Häberle J, Görg B, Toutain A, Rutsch F, Benoist JF, Gelot A, Suc AL, Koch HG, Schliess F, Häussinger D
J Inherit Metab Dis 2006 Apr-Jun;29(2-3):352-8. doi: 10.1007/s10545-006-0256-5. PMID: 16763901

Prognosis

Häberle J, Görg B, Toutain A, Rutsch F, Benoist JF, Gelot A, Suc AL, Koch HG, Schliess F, Häussinger D
J Inherit Metab Dis 2006 Apr-Jun;29(2-3):352-8. doi: 10.1007/s10545-006-0256-5. PMID: 16763901

Clinical prediction guides

Chang MC, Staklinski SJ, Malut VR, Pierre GL, Kilberg MS, Merritt ME
Nutrients 2023 Apr 18;15(8) doi: 10.3390/nu15081938. PMID: 37111157Free PMC Article
Staklinski SJ, Chang MC, Yu F, Collins Ruff K, Franz DN, Qian Z, Bloom LB, Merritt ME, McKenna R, Kilberg MS
J Biol Chem 2022 Sep;298(9):102385. Epub 2022 Aug 17 doi: 10.1016/j.jbc.2022.102385. PMID: 35985424Free PMC Article
Häberle J, Görg B, Toutain A, Rutsch F, Benoist JF, Gelot A, Suc AL, Koch HG, Schliess F, Häussinger D
J Inherit Metab Dis 2006 Apr-Jun;29(2-3):352-8. doi: 10.1007/s10545-006-0256-5. PMID: 16763901

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...