Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA

Parneet Kaur; Mirjam M C Wamelink; Marjo S van der Knaap; Katta Mohan Girisha; Anju Shukla

doi:10.1016/j.ejmg.2019.103708

Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA

Eur J Med Genet. 2019 Aug;62(8):103708. doi: 10.1016/j.ejmg.2019.103708. Epub 2019 Jun 25.

Authors

Parneet Kaur¹, Mirjam M C Wamelink², Marjo S van der Knaap³, Katta Mohan Girisha¹, Anju Shukla⁴

Affiliations

¹ Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.
² Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Metabolic Laboratory, Amsterdam Neuroscience, De Boelelaan, 1117, Amsterdam, the Netherlands.
³ Pediatric Neurology, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam Neuroscience, The Netherlands; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands.
⁴ Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India. Electronic address: anju.shukla@manipal.edu.

PMID: 31247379
DOI: 10.1016/j.ejmg.2019.103708

Abstract

Ribose 5-phosphate isomerase deficiency is a rare genetic leukoencephalopathy caused by pathogenic sequence variants in RPIA, that encodes ribose 5-phosphate isomerase, an enzyme in the pentose phosphate pathway. Till date, only three individuals with ribose 5-phosphate isomerase deficiency have been described in literature. We report on a subject with RPIA associated progressive leukoencephalopathy with elevated urine arabitol and ribitol levels and a novel missense variant c.770T > C p.(Ile257Thr) in exon 8 of RPIA. We also compare the phenotypes of all the four subjects. Our report confirms the phenotype and the genetic cause of this condition.

Keywords: Epilepsy; Leukoencephalopathy; Pentose phosphate pathway; RPIA; Ribose 5-phosphate isomerase deficiency.

Publication types

Case Reports

MeSH terms

Aldose-Ketose Isomerases / deficiency*
Aldose-Ketose Isomerases / genetics
Alleles
Carbohydrate Metabolism, Inborn Errors / drug therapy
Carbohydrate Metabolism, Inborn Errors / genetics*
Carbohydrate Metabolism, Inborn Errors / pathology
Humans
Leukoencephalopathies / drug therapy
Leukoencephalopathies / genetics*
Leukoencephalopathies / pathology
Male
Pentose Phosphate Pathway / genetics
Polyneuropathies / drug therapy
Polyneuropathies / genetics*
Polyneuropathies / pathology
Ribitol / administration & dosage
Sugar Alcohols / administration & dosage

Substances

Sugar Alcohols
Ribitol
Aldose-Ketose Isomerases
ribosephosphate isomerase
arabitol

Supplementary concepts

Ribose 5-Phosphate Isomerase Deficiency