AUTHOR=Fermo Elisa , Vercellati Cristina , Marcello Anna Paola , Zaninoni Anna , Aytac Selin , Cetin Mualla , Capolsini Ilaria , Casale Maddalena , Paci Sabrina , Zanella Alberto , Barcellini Wilma , Bianchi Paola 

TITLE=Clinical and Molecular Spectrum of Glucose-6-Phosphate Isomerase Deficiency. Report of 12 New Cases

JOURNAL=Frontiers in Physiology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.00467

DOI=10.3389/fphys.2019.00467

ISSN=1664-042X

ABSTRACT=Glucose-6-phosphate isomerase (GPI, EC 5.3.1.9) is a dimeric enzyme that catalyses the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate, the second reaction step of glycolysis. GPI deficiency, transmitted as an autosomal recessive trait, is considered the second most common erythro-enzymopathy of anaerobic glycolysis after pyruvate kinase deficiency. Despite of this, the defect may be sometime misdiagnosed and only about 60 cases of GPI deficiency have been reported. GPI deficient patients are affected by chronic non-spherocytic hemolytic anemia of variable severity; in rare cases, mental retardation or neuromuscular symptoms have also been reported. The gene locus encoding GPI is located on chromosome 19q13.1 and contains 18 exons. So far, about 40 causative mutations have been identified. 
We report the clinical, hematological and molecular characteristics of 12 GPI deficient cases (8 males, 4 females) from 11 families, with a median age at admission of 13 yrs (range 1-51);  8 of them were of Italian origin. 
Patients display moderate/severe anemia that improve with aging. Splenectomy doesn’t always result in amelioration of anemia, but may be considered in transfusion-dependent patients to reduce transfusion interval. 
None of the patients here described displayed neurological impairment attributable to the enzyme defect. We identified thirteen different mutations in GPI gene, 6 of them never described before; the new mutations affect highly conserved residues, were not detected in 1000 Genomes and HGMD databases, and were considered pathogenic by several mutation algorithms. 
This is the largest series of GPI deficient patients so far reported in a single study.  The study confirms the great heterogeneity of the molecular defect and gives new insight on clinical and molecular aspects of this disease.