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

Ethics Approval and Consent to Participate

Not applicable since this pertains to a clinical case description.

Consent for Publication

Written, informed consent was obtained from the parent to publish details about the index case as well as publish the genetic reports of the two parents. The father has signed the consent form giving consent for publication.

Availability of Data and Material

All clinical materials pertaining to this case are included in this article and are available with the corresponding author. We are happy to produce all information if any clarifications are requested.

Authors' Contribution

J.W. is the pediatric neurologist responsible for establishment of the diagnosis, managing the patient, and following up the infant over past 18 months. She was the main author in this case report. KJ is the author responsible for patient care during the hospital stay and has read the article and made significant contributions for improvement. EJ is the author responsible for the facilitation and interpretation of all biochemical assays in this patient. She has coordinated the molecular analysis of his gene mutation as well. She has read and made improvements to the manuscript. All authors have read the manuscript and agreed to the content of the case report.

Patient Perspective

The parents appreciated knowing the diagnosis in both their affected children. However, due to the financial and logistical difficulties in obtaining appropriate ketogenic formula, achieving optimal ketosis for the index case became a challenge.

Note

Centogene AG was generous to perform the molecular analysis of this infant free of charge.

Publication History

Received: 23 January 2023

Accepted: 15 March 2023

Article published online:
12 April 2023

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