title: Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis.
abstract: 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 humanGLULgene (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.
authors: Division of Metabolism and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032 Zurich, Switzerland. Marta.Spodenkiewicz@kispi.uzh.ch.
authors: Marta
authors: M
authors: Spodenkiewicz
authors: Division of Metabolism and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032 Zurich, Switzerland. Carmen.diez@kispi.uzh.ch.
authors: Carmen
authors: C
authors: Diez-Fernandez
authors: Division of Metabolism and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032 Zurich, Switzerland. Veronique.Ruefenacht@kispi.uzh.ch.
authors: Véronique
authors: V
authors: Rüfenacht
authors: Division of Metabolism and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032 Zurich, Switzerland. Corinne.gemperle@kispi.uzh.ch.
authors: Corinne
authors: C
authors: Gemperle-Britschgi
authors: Division of Metabolism and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032 Zurich, Switzerland. Johannes.Haeberle@kispi.uzh.ch.
authors: Johannes
authors: J
authors: Häberle
keywords: GLUL; GS deficiency; epileptic encephalopathy; glutamine synthetase; glutamine-glutamate-GABA; hyperammonemia; inborn error of metabolism; rare disease