Orphanet Journal of Rare Diseases

, 7:48

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Glutamine supplementation in a child with inherited GS deficiency improves the clinical status and partially corrects the peripheral and central amino acid imbalance

  • Johannes HäberleAffiliated withDivision of Metabolism and Children’s Research Center, University Children’s Hospital Zurich Email author 
  • , Noora ShahbeckAffiliated withSection of Clinical and Metabolic Genetics
  • , Khalid IbrahimAffiliated withSection of Pediatric Neurology, Department of Pediatrics, Hamad Medical Corporation
  • , Bernhard SchmittAffiliated withDivision of Neuropediatrics, University Children’s Hospital Zurich
  • , Ianina ScheerAffiliated withDivision of Radiology, University Children’s Hospital Zurich
  • , Ruth O’GormanAffiliated withCenter for Magnetic Resonance Research, University Children’s Hospital Zurich
  • , Farrukh A ChaudhryAffiliated withThe Biotechnology Centre and The Centre for Molecular Biology and Neuroscience, University of Oslo Email author 
  • , Tawfeg Ben-OmranAffiliated withSection of Clinical and Metabolic GeneticsDepartment of Pediatrics and Genetic Medicine, Weil-Cornell Medical CollegeDepartment of Pediatrics and Genetic Medicine, Weil-Cornell Medical College Email author 


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.


Glutamine supplementation Glutamine synthetase Chronic encephalopathy Neonatal onset seizures Hyperammonemia Qatar consanguinity Therapeutic trial GABA Neurotransmitter replenishment SLC38