{"Name":"Congenital brain dysgenesis due to glutamine synthetase deficiency","DiseaseID__c":"GARD:0009848","id":9848,"encodedName":"congenital-brain-dysgenesis-due-to-glutamine-synthetase-deficiency","IsDeleted":false,"Disease_Name_Full__c":"Congenital brain dysgenesis due to glutamine synthetase deficiency","Xref_IDs__c":"C1864910; C536832; DOID:0070544; MEDGEN:400638; MONDO:0012393; OMIM:610015; ORPHA:71278","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":4,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":0,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":0,"No_of_Disease_Descriptions__c":2,"Disease_Characteristics_Score__c":6,"No_of_Age_at_Onset__c":2,"Description_Source__c":"ORPHA:71278","Disease_Description__c":"A rare neurometabolic disease characterized by neonatal onset of severe epileptic encephalopathy with brain malformations (including cerebral and cerebellar atrophy, white matter abnormalities, delayed gyration or complete agyria, and thin corpus callosum), generalized hypotonia, and lack of normal development. Additional features include facial dysmorphism and necrolytic erythema of the skin. Biochemical hallmarks are decreased levels of glutamine in body fluids and chronic hyperammonemia. Death may occur in the early post-natal period due to multiple organ failure.","GARD_Name__c":"Congenital brain dysgenesis due to glutamine synthetase deficiency","GARD_Synonym__c":"glnd; glutamine synthase deficiency, congenital systemic; inherited glutamine synthetase deficiency; inherited gs deficiency","Curated_Disease_Description_Source__c":"ORPHA:71278","Curated_Disease_Description__c":"A rare neurometabolic disease characterized by neonatal onset of severe epileptic encephalopathy with brain malformations (including cerebral and cerebellar atrophy, white matter abnormalities, delayed gyration or complete agyria, and thin corpus callosum), generalized hypotonia, and lack of normal development. Additional features include facial dysmorphism and necrolytic erythema of the skin. Biochemical hallmarks are decreased levels of glutamine in body fluids and chronic hyperammonemia. Death may occur in the early post-natal period due to multiple organ failure.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as a Newborn and as an Infant","SourceID__c":"ORPHA:71278","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0012393","ORPHANET_ID__c":"ORPHA:71278","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Disgenesia cerebral congénita por deficiencia de glutamina sintetasa","Spanish_Description_Source__c":null,"Spanish_Description__c":null,"Spanish_Disease_Name__c":"disgenesia cerebral congénita por deficiencia de glutamina sintetasa","Spanish_GARD_Synonym__c":"deficiencia de glutamina sintetasa hereditaria; deficiencia de gs hereditario; deficiencia hereditaria de glutamina sintetasa; deficiencia hereditaria de gs","Category_Linearization__c":"ORPHA:98006","icd10_id__c":null,"mesh_id__c":null,"omim_id__c":null,"snomed_id__c":null,"umls_id__c":null,"GARD_Disease__c":[{"Curated_Disease_Description__c":"A rare neurometabolic disease characterized by neonatal onset of severe epileptic encephalopathy with brain malformations (including cerebral and cerebellar atrophy, white matter abnormalities, delayed gyration or complete agyria, and thin corpus callosum), generalized hypotonia, and lack of normal development. Additional features include facial dysmorphism and necrolytic erythema of the skin. Biochemical hallmarks are decreased levels of glutamine in body fluids and chronic hyperammonemia. Death may occur in the early post-natal period due to multiple organ failure.","Curated_Disease_Description_Source__c":"ORPHA:71278","GARD_Synonym__c":"glnd; glutamine synthase deficiency, congenital systemic; inherited glutamine synthetase deficiency; inherited gs deficiency","Name":"Congenital brain dysgenesis due to glutamine synthetase deficiency","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"GARD_Disease_Tag__c":[{"Tag_Name__c":"Genetics","Tag_Category__c":"Cause;Disease Category;Specialist","category_description":"Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.","curated_tag_name":"Genetic diseases"},{"Tag_Name__c":"Neurology","Tag_Category__c":"Disease Category;Specialist","category_description":"Neurological diseases affect the brain, spinal cord, cranial nerves, autonomic nerves, or other peripheral nerves.","curated_tag_name":"Neurological diseases"},{"Tag_Name__c":"Inborn Errors of Metabolism","Tag_Category__c":"Cause;Disease Category","category_description":"Inherited metabolic diseases, or inborn errors of metabolism, are a group of genetic diseases that affect the ability of the body's cells to convert food into energy.","curated_tag_name":"Inherited metabolic diseases"},{"Tag_Name__c":"Neurodevelopmental disabilities","Tag_Category__c":"Specialist","curated_tag_name":"Neurodevelopmental disabilities"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Neonatal","Provided_By__c":"ORPHA:71278"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:71278"}],"Diagnosis__c":[{"Type__c":"GTR","Curie__c":"MEDGEN:C1864910"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0009848","Source__c":"RareSource"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0070544","Source__c":"MONDO:0012393","Xref__c":"DOID:0070544"},{"URL__c":"https://www.orpha.net/en/disease/detail/71278","Source__c":"C1864910; MONDO:0012393","Xref__c":"ORPHA:71278"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C1864910","Source__c":"C1864910","Xref__c":"C1864910"},{"URL__c":"https://www.omim.org/entry/610015","Source__c":"C1864910; MONDO:0012393; ORPHA:71278","Xref__c":"OMIM:610015"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C536832","Source__c":"MONDO:0012393","Xref__c":"C536832"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=400638","Source__c":"C1864910","Xref__c":"MEDGEN:400638"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0012393","Source__c":"GARD:0009848","Xref__c":"MONDO:0012393"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"GLUL","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Increased breadth of the nasal bridge (and with it, the nasal root).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000431","HPO_Synonym__c":"Broad nasal bridge; Broad nasal root; Broadened nasal bridge; Increased breadth of bridge of nose; Increased breadth of nasal bridge; Increased width of bridge of nose; Increased width of nasal bridge; Nasal bridge broad; Nasal bridge, wide; Wide bridge of nose; Wide nasal bridge; Widened nasal bridge","HPO_Name__c":"Wide nasal bridge","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Abnormally decreased levels of glutamine in cerebrospinal fluid.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0500198","HPO_Synonym__c":"Low glutamine levels in cerebrospinal fluid","HPO_Name__c":"Decreased CSF glutamine concentration","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002205","HPO_Synonym__c":"Frequent respiratory infections; Multiple respiratory infections; Recurrent respiratory infections; respiratory infections, recurrent; Susceptibility to respiratory infections","HPO_Name__c":"Recurrent respiratory infections","Feature_System__c":"Respiratory system; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The presence of abnormally small extremities.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002983","HPO_Synonym__c":"Smaller or shorter than typical limbs","HPO_Name__c":"Micromelia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"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).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000463","HPO_Synonym__c":"Anteverted nose; Anteverted nostrils; Nasal tip, upturned; Nostrils anteverted; Upturned nares; Upturned nasal tip; Upturned nose; Upturned nostrils","HPO_Name__c":"Anteverted nares","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Increased intensity of the a reflex in the leg.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002395","HPO_Synonym__c":"Brisk lower extremity reflexes; Hyperreflexia in lower limbs; Hyperreflexia in the lower limbs; Increased deep tendon reflexes in the lower limbs; Leg hyperreflexia; Overactive lower leg reflex","HPO_Name__c":"Lower limb hyperreflexia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001250","HPO_Synonym__c":"Epileptic seizure; Seizures","HPO_Name__c":"Seizure","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","Feature__r":{"HPO_Description__c":"Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001298","HPO_Name__c":"Encephalopathy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001371","HPO_Synonym__c":"Flexed joint that cannot be straightened; Flexion contractures; Flexion contractures of joints","HPO_Name__c":"Flexion contracture","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001252","HPO_Synonym__c":"Low muscle tone; Low or weak muscle tone; Muscle hypotonia; Muscular hypotonia","HPO_Name__c":"Hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012385","HPO_Synonym__c":"Permanent flexion of the finger or toe","HPO_Name__c":"Camptodactyly","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0006956","HPO_Synonym__c":"Dilatation of lateral cerebral ventricles; Dilation of lateral ventricles; Enlarged lateral ventricles; Lateral ventricle dilatation","HPO_Name__c":"Lateral ventricle dilatation","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","Feature__r":{"HPO_Description__c":"Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003429","HPO_Name__c":"CNS hypomyelination","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Respiratory difficulty as newborn.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002643","HPO_Synonym__c":"Infantile respiratory distress; Neonatal respiratory distress; Newborn respiratory distress; Respiratory distress, neonatal","HPO_Name__c":"Neonatal respiratory distress","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003196","HPO_Synonym__c":"Decreased length of nose; Hypoplastic nose; Nasal hypoplasia; Short nose; Shortened nose","HPO_Name__c":"Short nose","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002104","HPO_Synonym__c":"Absence of spontaneous respiration; Apneic episodes; Apnoea","HPO_Name__c":"Apnea","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000369","HPO_Synonym__c":"Low set ears; Low-set ears; Low-set pinnae; Lowset ears; Melotia","HPO_Name__c":"Low-set ears","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0010783","HPO_Synonym__c":"Redness of skin or mucous membrane","HPO_Name__c":"Erythema","Feature_System__c":"Skin System; Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Decreased amount of glutamine in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0500147","HPO_Synonym__c":"Decreased blood glutamine concentration; Low blood glutamine level","HPO_Name__c":"Hypoglutaminemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A slower than normal heart rate (in adults, slower than 60 beats per minute).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001662","HPO_Synonym__c":"Brachycardia; Slow heartbeats","HPO_Name__c":"Bradycardia","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"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.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002416","HPO_Synonym__c":"Subependymal germinolytic cyst; Subependymal pseudocyst","HPO_Name__c":"Subependymal cysts","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Posterior positioning of the nasal root in relation to the overall facial profile for age.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0005280","HPO_Synonym__c":"Depressed bridge of nose; Depressed nasal bridge; Depressed nasal root; Flat bridge of nose; Flat nasal bridge; Flat nasal root; Flat, nasal bridge; Flattened nasal bridge; Low nasal bridge; Low nasal root; Retruded bridge of nose; Retruded nasal bridge","HPO_Name__c":"Depressed nasal bridge","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An increased concentration of ammonia in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001987","HPO_Synonym__c":"High blood ammonia levels","HPO_Name__c":"Hyperammonemia","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Underdevelopment of the corpus callosum.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002079","HPO_Synonym__c":"Corpus callosum hypoplasia; Hypoplasia of corpus callosum; Hypoplastic corpus callosum; Underdevelopment of part of brain called corpus callosum","HPO_Name__c":"Hypoplasia of the corpus callosum","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"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).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000233","HPO_Synonym__c":"Decreased volume of lip; Decreased volume of lip vermillion; Thin lips; Thin vermillion","HPO_Name__c":"Thin vermilion border","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A severe delay in the achievement of motor or mental milestones in the domains of development of a child.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011344","HPO_Synonym__c":"Global developmental delay, severe","HPO_Name__c":"Severe global developmental delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Partial or complete wasting (loss) of brain tissue that was once present.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012444","HPO_Synonym__c":"Brain degeneration; Brain wasting","HPO_Name__c":"Brain atrophy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"OMIM:610015","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Generalized muscular hypotonia (abnormally low muscle tone).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001290","HPO_Synonym__c":"Generalized decreased muscle tone; Generalized muscular hypotonia; Hypotonia, generalized","HPO_Name__c":"Generalized hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism"],"Disease Category":["Genetics","Neurology","Inborn Errors of Metabolism"],"Specialist":["Genetics","Neurology","Neurodevelopmental disabilities","Pediatrics"]},"synonyms":["glnd"," glutamine synthase deficiency, congenital systemic"," inherited glutamine synthetase deficiency"," inherited gs deficiency"]}