Clinical Information

Adenylate kinase (AK) is a monomeric enzyme that catalyzes the nucleotide phosphoryl interconversion of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) to 2 molecules of adenosine diphosphate (ADP). The level of enzyme activity in neonates is normally mildly to moderately lower than in adults. AK deficiency (OMIM 612631) is a rare cause of autosomal recessive nonspherocytic hemolytic anemia.

Although rare, AK deficient-associated anemia has been described in multiple families of varied ethnic origin. Those individuals with heterozygous genetic alterations are predominantly asymptomatic and show a normal phenotype. Those individuals with homozygous or compound heterozygous genetic alterations display congenital chronic nonspherocytic hemolytic anemia (hemoglobin [Hb] levels of 8-9 g/dL) with hyperbilirubinemia and gallstones. Patients typically present at birth or in early childhood. Some patients have psychomotor impairment, although the pathogenesis is not well understood. Concurrent glucose 6-phosphate dehydrogenase (G6PD) deficiency exacerbates the anemia (Hb 6 g/dL). AK activity levels range from 0% to 44%, although most show less than 30% activity. Carriers have normal to only mildly decreased enzyme activity (1). Patients may respond well to splenectomy.