Glutamine supplementation in a child with inherited GS deficiency improves the clinical status and partially corrects the peripheral and central amino acid imbalance
- Equal contributors
1 Division of Metabolism and Children’s Research Center, University Children’s Hospital Zurich, 8032, Zurich, Switzerland
2 Section of Clinical and Metabolic Genetics, Doha, Qatar
3 Section of Pediatric Neurology, Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar
4 Division of Neuropediatrics, University Children’s Hospital Zurich, Zurich, Switzerland
5 Division of Radiology, University Children’s Hospital Zurich, Zurich, Switzerland
6 Center for Magnetic Resonance Research, University Children’s Hospital Zurich, Zurich, Switzerland
7 The Biotechnology Centre and The Centre for Molecular Biology and Neuroscience, University of Oslo, Oslo, Norway
8 Department of Pediatrics and Genetic Medicine, Weil-Cornell Medical College, New York, USA
9 Department of Pediatrics and Genetic Medicine, Weil-Cornell Medical College, Doha, Qatar
Orphanet Journal of Rare Diseases 2012, 7:48 doi:10.1186/1750-1172-7-48Published: 25 July 2012
Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition.
Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy.
Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia.
In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage.