Autosomal Recessively Inherited Glucose Transporter-1 Deficiency Syndrome with Acanthocytosis: A Case Report

Abstract

Glucose transporter-1 deficiency syndrome (GLUT-1DS) is a rare, autosomal dominantly inherited disorder due to a heterozygous mutation in the gene solute channel 2A1 (SLC2A1).This gene encodes the glucose transporter protein-1. Autosomal recessive inheritance is extremely rare. Similarly, only very few reports are found in the literature of hematological manifestations in this syndrome. We report an autosomal recessively inherited GLUT-1DS, due to a de novo mutation, with the classical infantile presentation associated with concomitant acanthocytosis. In this case report, the second child born to consanguineous parents with initial refractory neonatal seizures and subsequent poorly controlled epilepsy and developmental regression is discussed. The most notable investigation findings supportive of his underlying diagnosis were very low cerebrospinal fluid (CSF) glucose and CSF lactate levels. His CSF:plasma glucose ratio was 1:7.6. He was anemic with a hemoglobin of 8.8 g/dL with his blood film showing marked acanthocytosis. His elder brother who also had refractory epilepsy and developmental regression had similar hypoglycorrhachia, low CSF:plasma glucose ratio, and mild anemia with acanthocytosis, and he died before establishment of a diagnosis. Our patient was diagnosed to have a novel mutation SLC2A1 c.184A > G p.(Thr62Ala), for which both parents were heterozygous, confirming autosomal recessive inheritance. Commencement of a ketogenic diet resulted in improvement of his seizures and slow gain in development. It also resulted in gradual disappearance of acanthocytes from his peripheral blood. This case describes a rare case of classical GLUT-1DS, autosomal recessively inherited, due to a novel mutation. The acanthocytosis in his blood smear is another rare association minimally reported in GLUT-1DS. The cause of his abnormal red blood cell morphology is unclear. It is possibly related to cation leakage reported in some rare mutations of the SLC2A1 gene needs reference.

Keywords

classical - glucose transporter-1 deficiency syndrome - red cell morphology

• References

• 1 Koepsell H. Glucose transporters in brain in health and disease. Pflugers Arch 2020; 472 (09) 1299-1343
• 2 Pascual JM, Wang D, Lecumberri B. et al. GLUT1 deficiency and other glucose transporter diseases. Eur J Endocrinol 2004; 150 (05) 627-633
• 3 Leen WG, Klepper J, Verbeek MM. et al. Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain 2010; 133 (Pt 3): 655-670
• 4 Gallagher PG. Disorders of erythrocyte hydration. Blood 2017; 130 (25) 2699-2708
• 5 Glogowska E, Gallagher PG. Disorders of erythrocyte volume homeostasis. Int J Lab Hematol 2015; 37 (01, Suppl 1): 85-91
• 6 Flatt JF, Guizouarn H, Burton NM. et al. Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome. Blood 2011; 118 (19) 5267-5277
• 7 Weber YG, Storch A, Wuttke TV. et al. GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak. J Clin Invest 2008; 118 (06) 2157-2168
• 8 Bawazir WM, Gevers EF, Flatt JF. et al. An infant with pseudohyperkalemia, hemolysis, and seizures: cation-leaky GLUT1-deficiency syndrome due to a SLC2A1 mutation. J Clin Endocrinol Metab 2012; 97 (06) E987-E993
• 9 Klepper J, Scheffer H, Elsaid MF, Kamsteeg EJ, Leferink M, Ben-Omran T. Autosomal recessive inheritance of GLUT1 deficiency syndrome. Neuropediatrics 2009; 40 (05) 207-210
• 10 Khan AA, Hanada T, Mohseni M. et al. Dematin and adducin provide a novel link between the spectrin cytoskeleton and human erythrocyte membrane by directly interacting with glucose transporter-1. J Biol Chem 2008; 283 (21) 14600-14609
• 11 Schwantje M, Verhagen LM, van Hasselt PM, Fuchs SA. Glucose transporter type 1 deficiency syndrome and the ketogenic diet. J Inherit Metab Dis 2020; 43 (02) 216-222