Glutathione Synthetase Deficiency (GSSD)

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OMIM 56 266130 KEGG 36 H02312 MESH via Orphanet 44 C536835 ICD10 via Orphanet 33 D55.1 UMLS via Orphanet 72 C0398746 C1291643

Orphanet 58 ORPHA289846 ORPHA32 MedGen 41 C0398746 SNOMED-CT via HPO 68 124706000 128613002 165517008 228156007 234589002 246545002 247578003 258211005 28835009 298282001 30721006 313307000 39112005 61261009 8011004 84757009 85102008 88425004 91138005 91175000 more UMLS 71 C0268525 C0398746

Genetics Home Reference : ²⁵ Glutathione synthetase deficiency is a disorder that prevents the production of an important molecule called glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components. Glutathione synthetase deficiency can be classified into three types: mild, moderate, and severe. Mild glutathione synthetase deficiency usually results in the destruction of red blood cells (hemolytic anemia). In addition, affected individuals may release large amounts of a compound called 5-oxoproline in their urine (5-oxoprolinuria). This compound builds up when glutathione is not processed correctly in cells. Individuals with moderate glutathione synthetase deficiency may experience symptoms beginning shortly after birth including hemolytic anemia, 5-oxoprolinuria, and elevated acidity in the blood and tissues (metabolic acidosis). In addition to the features present in moderate glutathione synthetase deficiency, individuals affected by the severe form of this disorder may experience neurological symptoms. These problems may include seizures; a generalized slowing down of physical reactions, movements, and speech (psychomotor retardation); intellectual disability; and a loss of coordination (ataxia). Some people with severe glutathione synthetase deficiency also develop recurrent bacterial infections.

MalaCards based summary : Glutathione Synthetase Deficiency, also known as pyroglutamic aciduria, is related to metabolic acidosis and hemolytic anemia, and has symptoms including vomiting, abdominal pain and diarrhea. An important gene associated with Glutathione Synthetase Deficiency is GSS (Glutathione Synthetase), and among its related pathways/superpathways are Glutathione metabolism and Ferroptosis. Affiliated tissues include brain, testes and neutrophil, and related phenotypes are hemolytic anemia and abnormality of immune system physiology

NIH Rare Diseases : ⁵² 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 variants or mutations ) 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 . Treatment for glutathione synthetase deficiency may include sodium bicarbonate to treat metabolic acidosis and taking vitamin supplements.

OMIM : ⁵⁶ Glutathione synthetase deficiency, or 5-oxoprolinuria, is an autosomal recessive disorder characterized, in its severe form, by massive urinary excretion of 5-oxoproline, metabolic acidosis, hemolytic anemia, and central nervous system damage. The metabolic defect results in decreased levels of cellular glutathione, which overstimulates the synthesis of gamma-glutamylcysteine and its subsequent conversion to 5-oxoproline (Larsson and Anderson, 2001). (266130)

KEGG : ³⁶ Glutathione synthetase deficiency is a rare autosomal recessive disorder. The clinical phenotype varies widely, and nearly 30 different mutations in the GSS gene have been identified. In severe form, it is characterized by massive urinary excretion of 5-oxoproline, metabolic acidosis, haemolytic anaemia and central nervous system damage. A milder form, which is only associated with haemolytic anaemia, has also been reported.

UniProtKB/Swiss-Prot : ⁷³ Glutathione synthetase deficiency: Severe form characterized by an increased rate of hemolysis and defective function of the central nervous system.

Wikipedia : ⁷⁴ Glutathione synthetase deficiency (GSD) is a rare autosomal recessive metabolic disorder that prevents... more...

Clinical features from OMIM:

266130

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