Childhood hypophosphatasia with homozygous mutation of ALPL.

Objective: To describe an unusual phenotype of a case with rare homozygous ALPL gene mutation that results in mild form of hypophosphatasia.

Methods: Case presentation, description of biochemical profiles, genetic testing and a brief review of literature are presented.

Results: A 13-year-old male presented with chronic left knee pain. Radiogram of the left knee indicated two oval radiolucent lesions in the femoral metaphysis. Serum alkaline phosphatase activity (17 U/L) was markedly below normal (42 to 362 U/L). Serum pyridoxal 5' phosphate (258 μg/L) was above normal (5 to 50 μg/L). Sequence analysis of ALPL gene indicated a homozygous missense mutation c.1077 C>G (p. I359M). The mutation was previously identified in a case of perinatal hypophosphatasia with severe skeletal abnormalities in contrast to the mild phenotype of the patient we present.

Conclusion: The case of homozygous mutation of ALPL gene but mild form of hypophosphatasia suggests that functions of the mutated protein may be modified by other factors.