Early Infantile Thiamine Transporter-2 Deficiency with Epileptic Spasms—A Phenotypic Spectrum with a Novel Mutation

Abstract

Epileptic seizures are a frequent feature of thiamine transporter deficiency that may present as a clinical continuum between severe epileptic encephalopathy and mixed focal or generalized seizures. Thiamine metabolism dysfunction syndrome 2 (MIM: 607483) or biotin-thiamine-responsive basal ganglia disease (BTBGD) due to biallelic pathogenic mutation in the SLC19A3 gene is a well-recognized cause of early infantile encephalopathy with a Leigh syndrome-like presentation and a lesser-known phenotype of atypical infantile spasms. We reported a 4-month-old infant who presented with progressive epileptic spasms since 1 month of age, psychomotor retardation, and lactic acidosis. Magnetic resonance imaging (MRI) revealed altered signal intensities in bilateral thalamic and basal ganglia, cerebellum, brainstem, cortical and subcortical white matter. Whole exome sequencing identified a homozygous ENST00000258403.3: c.871G > C (p.Gly291Arg) variant in the SLC19A3 gene. We elucidate the features in the proband, which were an amalgamation of both the above subtypes of the SLC19A3 associated with early infantile encephalopathy. We also highlight the features which were atypical for either “Leigh syndrome-like” or “atypical infantile spasm” phenotypes and suggest that the two separate entities can be merged as a clinical continuum. Treatment outcome with high-dose biotin and thiamine is promising. In addition, we report a novel pathogenic variant in the SLC19A3 gene.

Keywords

infantile spasms - biotin-thiamine-responsive - encephalopathy - thiamine - transporter - basal ganglia disease

Authors' Contributions

R.M. designed the study and prepared the initial draft of the manuscript. S.B.-M. made the diagnosis, supervised patient work-up, and management, revised and finalized the manuscript. R.K.S. and P.K. did the clinical evaluation of the case and R.K.S. was also in charge of overall patient management. T.B.S.B. did the MRI and its reporting. S.K. did NGS analysis and variant confirmation. J.K. did the protein modeling. D.G. performed Sanger sequencing of the identified variant. R.S. supervised Sanger sequencing and the analysis of the identified variant.

Ethical Approval

Approval of the Institute of Ethics Committee was not needed as the genetic testing of the patient was done for clinical diagnosis only. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Institutional and National) and with the 1975 Declaration of Helsinki, as received in 2008.

Informed Consent

Informed consent from the patient's parents was obtained.

Publication History

Received: 31 January 2021

Accepted: 27 April 2021

Article published online:
24 June 2021

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