Rare Etiology of Isolated Macrocytosis: Adenosine Kinase Deficiency With a Novel Mutation

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Adenosine kinase (ADK) deficiency is a rare autosomal recessive disorder affecting methionine and adenosine metabolism.
• It typically presents with psychomotor delay, epilepsy, dysmorphic features, and liver disease.

Purpose of the Study:

• To report a novel mutation in the ADK gene.
• To highlight ADK deficiency in the differential diagnosis of isolated macrocytosis, even in the absence of neurological symptoms.

Main Methods:

• Whole-exome sequencing was employed to identify genetic mutations.
• Clinical and laboratory findings of the patient were analyzed.

Main Results:

• A novel homozygous mutation (NM_006721.4 c.515A>C, p.Asn172Thr) in the ADK gene was identified.
• The patient presented with reticulocytosis, hyperbilirubinemia, elevated mean corpuscular volume, and hypermethioninemia, but without mental-motor developmental delay.

Conclusions:

• ADK deficiency should be considered in patients with isolated macrocytosis, irrespective of the presence of neurological delay.
• This finding expands the clinical spectrum of ADK deficiency and emphasizes the importance of biochemical screening.