Инфантильная форма гипофосфатазии: клинический случай

Abstract

Background . Hypophosphatasia is rare hereditary disease caused by deficiency of the tissue-nonspecific alkaline phosphatase isozyme. It manifests with bone and teeth mineralisation defects, electrolyte imbalance, respiratory disorders, convulsive syndrome, physical developmental delay, nephrocalcinosis. The rarity of this disease, clinical polymorphism, non-specificity of complains and signs are the major reasons of hypophosphatasia late diagnosis. The enzyme replacement therapy with recombinant alkaline phosphatase (asfotase alfa) can be used for treatment of severe forms of disease. Clinical Case Description . The girl (1 y 4 m) was routinely admitted with complains of physical developmental delay and psychomotor retardation, deformation of lower limbs, chest, gait abnormality, teeth loss and with diagnosis «protein-calorie malnutrition». Rickets-like changes in skeleton, myopathic syndrome, early normal teeth loss, hepatomegaly were revealed. Reduced activity of alkaline phosphatase in blood serum (33 u/l; reference range 156–369 u/l) was revealed. The infantile hypophosphatasia has been diagnosed. Due to molecular genetic testing of ALPL gene we revealed pathogenic variants c.526G>A (p.Ala176Thr) and c.1375G>A (p.Val459Met) in compound heterozygous state. The asphotase alpha therapy was initiated at the age of 1 y 10 m, the dose was 2 mg/kg subcutaneously 3 times a week. The results of 6 months of the therapy are the following: significant increase in the activity of alkaline phosphatase (maximum 4400 u/l), body weight (+ 2 kg), growth (+ 6 cm), reduction of bone deformation, normalisation of muscle tone and gait, exercise tolerance. The patient tolerated the drug administration well. Rarely there were hyperemia zones up to 4 cm in diameter with moderate induration at the injection site but they spontaneous disappeared in 2–3 days though. Conclusion. Patients with rickets-like diseases and low alkaline phosphatase activity requires performing of molecular genetic testing to confirm hypophosphatasia. Timely diagnosis and early initiation of enzyme replacement therapy can significantly improve the quality of life of children with hypophosphatasia.