Rare hereditary nonspherocytic hemolytic anemia caused by novel homozygous mutation, c.301C>A, (Q101K) in the AK1 gene in an Indian family

Abstract

BackgroundAdenylate kinase (AK) deficiency is an uncommon form of congenital non-spherocytic haemolytic anaemia. To date, only 13 families have been affected by this disorder exhibiting symptoms like chronic anaemia supported by recurrent blood transfusions, jaundice, hepatosplenomegaly, and mental and psychomotor retardation in exceptional cases. This study aimed to identify a pathogenic mutation in the undiagnosed case of haemolytic anemia and to offer a parental diagnosis in the subsequent pregnancy.MethodNext-generation sequencing (NGS) was performed to identify pathogenic variants in the patient. Prenatal diagnosis during the second pregnancy was performed on genetic testing was performed on chronic villus sample (CVS) collected in 11 weeks of pregnancy from the mother and intravenous blood was drawn from both the parents.ResultsNovel causative mutation (p. Gln101Lys) in the AK gene was identified in a 5-year-old male child with severe transfusion-dependent hemolytic anemia. Bioinformatics tools predicted the deleterious effect of the novel variant on the structure of the protein. Prenatal diagnosis of the fetus was found to be heterozygous for the mutation. Both the parents were heterozygous for the variant c.301C > A, p. Gln101Lys.ConclusionWe have presented a review of the literature and novel mutations in the AK1 gene (p. Gln101Lys) associated with adenylate kinase deficiency. It is first a prenatal diagnosis AK deficiency report from India where heterogeneity is too high in the population and custom of intra-community marriages are prevalent.