To the Editor: An 8-y-old girl from Odisha, product of non-consanguineous marriage with uneventful antenatal and postnatal history was referred to us for workup of severe anemia. She became symptomatic from 6 mo of age, receiving regular blood transfusions at 1–2 mo intervals. On examination, she had severe pallor and icterus with splenohepatomegaly. Lab investigations were suggestive of hemolytic picture {Hb: 3.0 g/dl, LDH: 1775, Reticulocyte count: 13.5%, peripheral smear: normocytic normochromic, unconjugated hyperbilirubinemia [Bilirubin (Total/Direct): 6.9/0.7]}. HPLC of the child and both parents were normal. Direct Coombs test and osmotic fragility test were also non-contributory. Hence, a strong probability of erythrocyte enzymopathies was kept, however, G6PD and pyruvate kinase were in normal range. So, possibility of other rare enzymopathies was considered, but as their estimation is not commercially available, Next-generation sequencing (NGS) was conducted which revealed a novel homozygous missense mutation in exon 7 of Adenylate kinase (AK1) gene (c.518T>G) causing amino acid substitution of Glycine for Valine at codon 173 (p. Val173Gly).

Erythrocyte adenylate kinase (AK) deficiency is an extremely rare cause of congenital hemolytic anemia [1], to date described only in 14 unrelated families worldwide. It is inherited in autosomal recessive manner and 11 specific mutations in AK1 gene have been described in literature so far [2]. Our patient had a novel homozygous missense mutation of AK1 gene that has not yet been reported in literature. Moreover, this is the fourth case of AK deficiency to be reported from India and first such case from eastern part of country [3, 4].

In conclusion, AK deficiency should be kept in differential diagnosis of hereditary anemias unexplainable by hemoglobinopathies, RBC membrane defects or common enzymopathies like G6PD deficiency. However, enzyme assay for such rare enzymopathies is not readily available commercially, posing a diagnostic challenge to clinicians. Such cases mandate NGS for confirmation of diagnosis.