Diagnosis of red blood cell hexokinase deficiency and literature review

Abstract

Objective To investigate the value of gene sequencing and protein conformation in the diagnosis process by reporting a case of erythrocyte hexokinase deficiency and reviewing relevant literature. Methods One patient with erythrocyte hexokinase deficiency and his families in the pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University on May 23, 2016 were selected as the research objects. Clinical data was collected from the initial records by retrospective analysis. Pathogenic gene was detected by target sequence capture and next generation high-throughput sequencing, and the effects of mutant genes on hexokinase function were studied by observing changes in the 3-dimensional structure of proteins. Results The patient exhibited chronic hemolytic anemia after birth. The high-throughput second-generation gene sequencing result of the DNA sample of the child showed that a de novo mutation in the HK1 gene located on chromosome 10, the substitution of cytidine at site 34 of exon1 by thymine : NM_033496: exon1: c. C34T: p. Arg12X, which was a nonsense mutation. Bioinformatics analysis and protein function simulation confirmed that the mutation of the gene can lead to the premature termination of the synthesis of the peptide chain. The short peptide synthesized after the mutation does not contain the binding group and catalytic group of the erythrocyte hexokinase, resulting in the loss of enzyme activity. The patient was eventually diagnosed with erythrocyte hexokinase-deficient hemolytic anemia caused by the HK1 gene mutation. Conclusions In clinical practice, patients with chronic non-spherical erythrocyte hemolytic anemia should be alert to erythrocyte hexosaminidase deficiency disease. Those with conditions should be diagnosed by gene sequencing and protein configuration analysis. Key words: Hexokinase deficiency; Hemolytic anemia; Sequence analysis; Protein structure, quaternary; HK1 gene