Neuropediatrics 2019; 50(01): 051-053
DOI: 10.1055/s-0038-1675637
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

A Very Rare Etiology of Hypotonia and Seizures: Congenital Glutamine Synthetase Deficiency

Özlem Ünal
1   Division of Metabolism and Nutrition, University of Health Sciences, Ankara Child Health and Diseases, Hematology Oncology Training and Research Hospital, Kurtdereli Sokak, Ankara, Turkey
,
Serdar Ceylaner
2   Intergen Genetic Diagnosis Center, Kavaklıdere, Ankara, Turkey
,
Rıdvan Akın
3   Division of Pediatric Neurology, Lösante Children's and Adult Hospital, Gölbaşı, Ankara, Turkey
› Author Affiliations
Further Information

Publication History

05 February 2018

30 September 2018

Publication Date:
15 November 2018 (online)

Abstract

Mutations in the human GLUL gene, which encodes the enzyme glutamine synthetase (GS), may cause congenital glutamine synthetase deficiency. The disease was first described in 2005 and only three patients have been reported to date. We report a fourth patient suffering from congenital GS deficiency who was found to have some distinctive clinical findings. The patient was a 30-month-old girl who was referred to us due to developmental delay and seizures which began at 5 months of age. She was seizure free for 5 months with valproic acid and vigabatrin. At presentation, she was found to have microcephaly and hypotonia. Her plasma glutamine concentration was near normal and she had mild hyperammonemia. Cranial magnetic resonance imaging (MRI) showed mild changes. Whole exome sequencing (WES) revealed a homozygous c.121C > T (p.R41C) (p.Arg41Cys) pathogenic variant of the GLUL gene. The diagnosis of this patient underlines the importance of careful evaluation of patients with borderline low glutamine levels. Treatment was begun with L-glutamine and nicotinamide and biochemical improvements have been observed at 6 months of follow-up. The outcome of this patient may provide important data about the effectiveness of glutamine and nicotinamide treatment in patients with congenital GS deficiency.

 
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