Clinical, laboratory, and mutational profile of children with glucose phosphate isomerase deficiency: a single centre report.

Glucose phosphate isomerase (GPI) deficiency is an autosomal recessive condition with mutations in the GPI gene on chromosome 19q13.1. Patients present with congenital non-spherocytic hemolytic anemia, and occasionally intellectual disability. In this study, we describe the clinical, hematological and biochemical parameters in the largest single-center cohort consisting of 17 GPI-deficient cases. Demographic and clinical data were noted, and red cell enzyme activity levels were estimated. Mutation analysis was done by single-stranded-conformation polymorphism, restriction-fragment length polymorphism and Sanger's sequencing of exon 12 of the GPI gene. The male-to-female ratio was 0.7:1, median age at diagnosis was 5.0 years, 82.3% of patients had severe neonatal jaundice, and 13.3% had subtle neurological manifestations. Median Hb and MCV levels were 6.3 g/dl and 130.2 fl. Splenectomized patients required fewer transfusions. Sixteen of 17 patients had the pathogenic c.1040G > A (p.Arg347His) homozygous mutation in exon12 of the GPI gene, and one had the pathogenic c.1414C > T(p.Arg472Cys) homozygous mutation in exon 16. In summary, we report that neonatal jaundice, macrocytosis and high prevalence of p.Arg347His variant were predominant in GPI deficiency with prominent lack of neurological manifestations, and we emphasize the benefits of splenectomy and the need for genetic counseling.