{"Name":"Inherited glutathione synthetase deficiency","DiseaseID__c":"GARD:0010047","id":10047,"encodedName":"inherited-glutathione-synthetase-deficiency","IsDeleted":false,"Disease_Name_Full__c":"Inherited glutathione synthetase deficiency","Xref_IDs__c":"234589002; C128193; C536835; C5979912; DOID:0080699; MEDGEN:1876682; MONDO:0017909; ORPHA:32","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":5,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":1,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":1,"No_of_Disease_Descriptions__c":4,"Disease_Characteristics_Score__c":7,"No_of_Age_at_Onset__c":1,"Description_Source__c":"MONDO:0017909","Disease_Description__c":"A rare disorder characterised by hemolytic anemia, associated with metabolic acidosis and 5-oxoprolinuria in moderate forms, and with progressive neurological symptoms and recurrent bacterial infections in the most severe forms.","GARD_Name__c":"Inherited glutathione synthetase deficiency","GARD_Synonym__c":"5-oxoprolinuria; glutathione synthetase deficiency; gssd; inborn error of glutathione synthase activity; inborn glutathione synthase activity disorder; pyroglutamic aciduria; pyroglutamicaciduria; rare inborn error of glutathione synthase activity","Curated_Disease_Description_Source__c":"GARD:0010047","Curated_Disease_Description__c":"Glutathione synthetase deficiency is a genetic metabolic disorder that affects the body's ability to produce an important substance called glutathione. People with Glutathione synthetase deficiency do not have enough of the molecule called glutathione synthetase, which helps the body produce glutathione. People with Glutathione synthetase deficiency can have mild, moderate, or severe disease. The signs and symptoms of the deficiency may include anemia, the buildup of too much acid in the body (metabolic acidosis), frequent infections, and symptoms caused by problems in the brain including seizures, intellectual disability, and loss of coordination (ataxia). Glutathione synthetase deficiency is caused by genetic changes (pathogenic variantss) in the GSS gene. The deficiency is inherited in an autosomal recessive manner. Diagnosis of a metabolic disorder such as Glutathione synthetase deficiency may be suspected when a doctor observes signs of the deficiency including metabolic acidosis. A doctor may order tests to confirm the diagnosis including enzyme assays, urine analysis, and genetic testing.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as a Newborn","SourceID__c":"ORPHA:32","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Grouping","MONDO_ID__c":"MONDO:0017909","ORPHANET_ID__c":"ORPHA:32","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Deficiencia de glutatión sintetasa","Spanish_Description_Source__c":"ORPHA:32","Spanish_Description__c":"Es un trastorno poco frecuente caracterizado por anemia hemolítica asociada a acidosis metabólica y 5-oxoprolinuria en las formas moderadas, y a síntomas neurológicos progresivos e infecciones bacterianas recurrentes en las formas más graves.","Spanish_Disease_Name__c":"deficiencia de glutatión sintetasa","Spanish_GARD_Synonym__c":"aciduria piroglutámica","Category_Linearization__c":"ORPHA:97992","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":"Glutathione synthetase deficiency is a genetic metabolic disorder that affects the body's ability to produce an important substance called glutathione. People with Glutathione synthetase deficiency do not have enough of the molecule called glutathione synthetase, which helps the body produce glutathione. People with Glutathione synthetase deficiency can have mild, moderate, or severe disease. The signs and symptoms of the deficiency may include anemia, the buildup of too much acid in the body (metabolic acidosis), frequent infections, and symptoms caused by problems in the brain including seizures, intellectual disability, and loss of coordination (ataxia). Glutathione synthetase deficiency is caused by genetic changes (pathogenic variantss) in the GSS gene. The deficiency is inherited in an autosomal recessive manner. Diagnosis of a metabolic disorder such as Glutathione synthetase deficiency may be suspected when a doctor observes signs of the deficiency including metabolic acidosis. A doctor may order tests to confirm the diagnosis including enzyme assays, urine analysis, and genetic testing.","Curated_Disease_Description_Source__c":"GARD:0010047","GARD_Synonym__c":"5-oxoprolinuria; glutathione synthetase deficiency; gssd; inborn error of glutathione synthase activity; inborn glutathione synthase activity disorder; pyroglutamic aciduria; pyroglutamicaciduria; rare inborn error of glutathione synthase activity","Name":"Inherited glutathione synthetase deficiency","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Childhood Dementia Initiative","Website__c":"https://www.childhooddementia.org/"},{"Account_Name__c":"Metabolic Support UK","Website__c":"https://www.metabolicsupportuk.org"},{"Account_Name__c":"Organic Acidemia Association","Website__c":"https://oaanews.org/"}],"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":"Hematology","Tag_Category__c":"Disease Category;Specialist","category_description":"Blood diseases affect the blood or blood-forming organs, including red blood cells, white blood cells, platelets, plasma, and bone marrow.","curated_tag_name":"Blood 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:32"}],"Diagnosis__c":[{"Type__c":"NEWBORN","Category__c":"Other","Curie__c":"http://newbornscreeningcodes.nlm.nih.gov/nb/sc/condition/5-OXO"},{"Type__c":"GTR","Curie__c":"MEDGEN:C0398746"}],"External_Identifier_Disease__c":[{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C536835","Source__c":"MONDO:0017909","Xref__c":"C536835"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0080699","Source__c":"MONDO:0017909","Xref__c":"DOID:0080699"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=234589002","Source__c":"C5979912; MONDO:0017909","Xref__c":"234589002"},{"URL__c":"https://www.orpha.net/en/disease/detail/32","Source__c":"C5979912; MONDO:0017909","Xref__c":"ORPHA:32"},{"URL__c":"https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C128193","Source__c":"MONDO:0017909","Xref__c":"C128193"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0017909","Source__c":"GARD:0010047","Xref__c":"MONDO:0017909"},{"URL__c":"https://medlineplus.gov/genetics/condition/glutathione-synthetase-deficiency"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=1876682","Source__c":"C5979912","Xref__c":"MEDGEN:1876682"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C5979912","Source__c":"C5979912","Xref__c":"C5979912"}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Longstanding metabolic acidosis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001996","HPO_Name__c":"Chronic metabolic acidosis","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Reduced level of the enzyme glutathione synthetase, which catalyzes the last step in the synthesis of glutathione and a deficiency results in low levels of glutathione. Acidosis is due to reduced feedback inhibition of gamma-glutamyl cysteine synthetase in the gamma-glutamyl cycle, which ultimately leads to overproduction and accumulation of 5-oxoproline.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003343","HPO_Synonym__c":"Glutathione synthetase deficiency","HPO_Name__c":"Reduced glutathione synthetase level","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A functional abnormality of the immune system.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0010978","HPO_Name__c":"Abnormality of immune system physiology","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A type of anemia caused by premature destruction of red blood cells (hemolysis).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001878","HPO_Synonym__c":"Haemolytic anemia; Increased hemolysis","HPO_Name__c":"Hemolytic anemia","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An abnormality of the nervous system.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000707","HPO_Synonym__c":"Abnormality of the nervous system; Neurologic abnormalities; Neurological abnormality","HPO_Name__c":"Abnormality of the nervous system","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002718","HPO_Synonym__c":"Bacterial infections, recurrent; Frequent bacterial infections; Frequent pyogenic infections; Increased susceptibility to bacterial infections; Recurrent bacterial infections; Recurrent major bacterial infections; Recurrent pyogenic infections; Susceptibility to pyogenic infection","HPO_Name__c":"Recurrent bacterial infections","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Concentration of glutathione in red blood cells below the lower limit of normal. Glutathione (GSH) is an important redox active biomolecule critical in the maintenance and regulation of cellular and organismal health.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0034738","HPO_Name__c":"Reduced erythrocyte glutathione concentration","Feature_System__c":"Blood and Blood-Forming Tissue","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An increase in the level of L-pyroglutamic acid in the urine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0410132","HPO_Synonym__c":"Elevated urine 5-oxoproline; Increased level of 5-oxo-L-proline in urine","HPO_Name__c":"Increased level of L-pyroglutamic acid in urine","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001249","HPO_Synonym__c":"Intellectual disability; Mental deficiency; Mental retardation; Mental retardation, nonspecific; Mental-retardation; Nonprogressive intellectual disability; Nonprogressive mental retardation","HPO_Name__c":"Intellectual disability","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001257","HPO_Synonym__c":"Involuntary muscle stiffness, contraction, or spasm; Muscle spasticity; Muscular spasticity","HPO_Name__c":"Spasticity","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008872","HPO_Name__c":"Feeding difficulties in infancy","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000952","HPO_Synonym__c":"Icterus; Jaundice; Yellow skin; Yellowing of the skin","HPO_Name__c":"Jaundice","Feature_System__c":"Skin System; Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:32","HPO_Frequency__c":"Frequent (30-79%)","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":"ORPHA:32","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Ataxia refers to impaired coordination of voluntary muscle movement. 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).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001251","HPO_Synonym__c":"Cerebellar ataxia","HPO_Name__c":"Ataxia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Inborn Errors of Metabolism"],"Disease Category":["Genetics","Neurology","Hematology","Inborn Errors of Metabolism"],"Specialist":["Genetics","Neurology","Hematology","Neurodevelopmental disabilities","Pediatrics"]},"synonyms":["5-oxoprolinuria"," glutathione synthetase deficiency"," gssd"," inborn error of glutathione synthase activity"," inborn glutathione synthase activity disorder"," pyroglutamic aciduria"," pyroglutamicaciduria"," rare inborn error of glutathione synthase activity"]}