A case of complete adenylate kinase deficiency due to a nonsense mutation in AK-1 gene (Arg 107 → Stop, CGA → TGA) associated with chronic haemolytic anaemia


Dr Alberto Zanella Divisione di Ematologia, Padiglione Granelli, IRCCS Ospedale Maggiore, Via F. Sforza 35, 20122 Milano, Italy. e-mail: div_emat@polic.cilea.it.


Two siblings of Italian origin with mild chronic haemolytic anaemia, psychomotor impairment and undetectable adenylate kinase (AK) activity are reported. The other red cell enzyme activities were normal except for a slight decrease of PFK. 2,3-DPG levels were increased in both siblings, and AMP decreased in one only. The parents were not consanguineous and displayed intermediate AK activity. The sequence of complete erythrocyte AK-1 cDNA showed the presence of a nonsense homozygous mutation at codon 107 (CGA → TGA, Arg → Stop) in the siblings. The mutation results in a truncated protein of 107 amino acids in comparison with the 194 of the normal one. Moreover a 37 bp deletion in the first part of exon 6 (from nt 326 to nt 362 of the cDNA sequence) was detected in one allele; this deletion is not likely to further affect the enzyme structure, being localized after the stop codon. The new variant was named AK Fidenza, from the origin of the patients.