Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis
Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a...
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MDPI AG
2016-10-01
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| Series: | Biology |
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| Online Access: | http://www.mdpi.com/2079-7737/5/4/40 |
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| author | Marta Spodenkiewicz Carmen Diez-Fernandez Véronique Rüfenacht Corinne Gemperle-Britschgi Johannes Häberle |
| author_facet | Marta Spodenkiewicz Carmen Diez-Fernandez Véronique Rüfenacht Corinne Gemperle-Britschgi Johannes Häberle |
| author_sort | Marta Spodenkiewicz |
| collection | DOAJ |
| description | Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS) can cause an ultra-rare recessive inborn error of metabolism—congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy. The hallmark of GS deficiency in these patients was decreased levels of glutamine in body fluids, associated with chronic hyperammonemia. This review aims at recapitulating the clinical history of the three known patients with congenital GS deficiency and summarizes the findings from studies done along with the work-up of these patients. It is the aim of this paper to convince the reader that (i) this disorder is possibly underdiagnosed, since decreased concentrations of metabolites do not receive the attention they deserve; and (ii) early detection of GS deficiency may help to improve the outcome of patients who could be treated early with metabolites that are lacking in this condition. |
| first_indexed | 2024-03-12T09:19:00Z |
| format | Article |
| id | doaj.art-498bfb6833764ea1ba77473a2ae96ab3 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-12T09:19:00Z |
| publishDate | 2016-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-498bfb6833764ea1ba77473a2ae96ab32023-09-02T14:36:36ZengMDPI AGBiology2079-77372016-10-01544010.3390/biology5040040biology5040040Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid BiosynthesisMarta Spodenkiewicz0Carmen Diez-Fernandez1Véronique Rüfenacht2Corinne Gemperle-Britschgi3Johannes Häberle4Division of Metabolism and Children’s Research Center, University Children’s Hospital, Steinwiesstr. 75, 8032 Zurich, SwitzerlandDivision of Metabolism and Children’s Research Center, University Children’s Hospital, Steinwiesstr. 75, 8032 Zurich, SwitzerlandDivision of Metabolism and Children’s Research Center, University Children’s Hospital, Steinwiesstr. 75, 8032 Zurich, SwitzerlandDivision of Metabolism and Children’s Research Center, University Children’s Hospital, Steinwiesstr. 75, 8032 Zurich, SwitzerlandDivision of Metabolism and Children’s Research Center, University Children’s Hospital, Steinwiesstr. 75, 8032 Zurich, SwitzerlandGlutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS) can cause an ultra-rare recessive inborn error of metabolism—congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy. The hallmark of GS deficiency in these patients was decreased levels of glutamine in body fluids, associated with chronic hyperammonemia. This review aims at recapitulating the clinical history of the three known patients with congenital GS deficiency and summarizes the findings from studies done along with the work-up of these patients. It is the aim of this paper to convince the reader that (i) this disorder is possibly underdiagnosed, since decreased concentrations of metabolites do not receive the attention they deserve; and (ii) early detection of GS deficiency may help to improve the outcome of patients who could be treated early with metabolites that are lacking in this condition.http://www.mdpi.com/2079-7737/5/4/40glutamine synthetaserare diseaseGLULepileptic encephalopathyGS deficiencyglutamine-glutamate-GABAhyperammonemiainborn error of metabolism |
| spellingShingle | Marta Spodenkiewicz Carmen Diez-Fernandez Véronique Rüfenacht Corinne Gemperle-Britschgi Johannes Häberle Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis Biology glutamine synthetase rare disease GLUL epileptic encephalopathy GS deficiency glutamine-glutamate-GABA hyperammonemia inborn error of metabolism |
| title | Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis |
| title_full | Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis |
| title_fullStr | Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis |
| title_full_unstemmed | Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis |
| title_short | Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis |
| title_sort | minireview on glutamine synthetase deficiency an ultra rare inborn error of amino acid biosynthesis |
| topic | glutamine synthetase rare disease GLUL epileptic encephalopathy GS deficiency glutamine-glutamate-GABA hyperammonemia inborn error of metabolism |
| url | http://www.mdpi.com/2079-7737/5/4/40 |
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