vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v18i6.2065vsp-2259Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONSИнфантильная форма гипофосфатазии: клинический случайInfantile Hypophosphatasia: Clinical Casehttps://orcid.org/0000-0002-7931-2263ГабрусскаяТ. В.GabrusskayaTatyana V.https://orcid.org/0000-0002-0570-1266ПанютинаЯ. В.PanutinaYana V.https://orcid.org/0000-0002-3537-7372РевноваМ. О.RevnovaMaria O.https://orcid.org/0000-0002-1180-8086КостикМ. М.KostikMikhail M.

Костик Михаил Михайлович - доктор медицинских наук, профессор кафедры госпитальной педиатрии СПбГПМУ.

194100, Санкт-Петербург, ул. Литовская, д. 2,  тел.: +7 (812) 416-52-98

kost-mikhail@yandex.ruСанкт-Петербургский государственный педиатрический медицинский университетРоссияSt. Petersburg State Pediatric Medical UniversityRussian FederationСанкт-Петербургский государственный педиатрический медицинский университет; Национальный медицинский исследовательский центр им. В.А. АлмазоваРоссияSt. Petersburg State Pediatric Medical University; Almazov National Medical Research CentreRussian Federation201917022020186452457Copyright © Габрусская Т.В., Панютина Я.В., Ревнова М.О., Костик М.М., 20202020Габрусская Т.В., Панютина Я.В., Ревнова М.О., Костик М.М.Gabrusskaya T.V., Panutina Y.V., Revnova M.O., Kostik M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/2259Обоснование

Обоснование. Гипофосфатазия — редкое наследственное заболевание, вызванное дефицитом изофермента тканенеспецифичной щелочной фосфатазы, проявляется нарушением минерализации костей и зубов, электролитными и дыхательными нарушениями, судорожным синдромом, задержкой физического развития, нефрокальцинозом. Редкость заболевания, полиморфизм клинических проявлений, неспецифичность жалоб являются причиной поздней диагностики гипофосфатазии. Для лечения тяжелых форм заболевания применяется ферментозаместительная терапия рекомбинантной щелочной фосфатазой — асфотазой альфа.

Описание клинического случая. Девочка, возраст 1 год 4 мес, госпитализирована в плановом порядке с жалобами на задержку физического и психомоторного развития, деформацию нижних конечностей, грудной клетки, нарушение походки, выпадение зубов, с диагнозом «белково-калорийная недостаточность». Отмечены рахитоподобные изменения скелета, миопатический синдром, раннее выпадение неизмененных зубов, гепатомегалия. Выявлена сниженная активность щелочной фосфатазы в сыворотке крови (33 Ед/л; норма 156–369 Ед/л). Диагностирована инфантильная форма гипофосфатазии. При молекулярногенетическом исследовании в гене ALPL обнаружены патогенные варианты c.526G>A (p.Ala176Thr) и c.1375G>A (p/Val459Met) в компаунд-гетерозиготном состоянии, подтвердившие диагноз. В возрасте 1 года 10 мес была начата терапия асфотазой альфа в дозировке 2 мг/кг массы тела подкожно 3 раза в неделю. За 6 мес терапии наблюдали значительное увеличение активности щелочной фосфатазы (максимально 4400 Ед/л), массы тела (+2 кг), роста (+6 см), уменьшение выраженности костных деформаций, восстановление мышечного тонуса, нормализацию походки, повышение толерантности к физическим нагрузкам. Введение препарата переносила удовлетворительно. Редко в месте инъекции отмечали появление гиперемии до 4 см в диаметре с умеренным уплотнением, которая самостоятельно разрешалась в течение 2–3 сут.

Заключение

Заключение. Пациентам с рахитоподобными заболеваниями с низкой активностью щелочной фосфатазы необходима генетическая диагностика для подтверждения гипофосфатазии. Своевременная диагностика и назначение ферментозаместительной терапии может существенно улучшить качество жизни детей с гипофосфатазией.

Background

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

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.

детигипофосфатазиярахитоподобные заболеваниящелочная фосфатазаасфотаза альфаген ALPLchildrenhypophosphatasiarickets-like diseasesalkaline phosphataseasfotase alfaALPL geneСтатья опубликована при поддержке компании «Свикс Биофарма». Вместе с тем авторы заявляют, что исследование клинического случая проводилось независимо от компании-производителя асфотазы альфаThe article has been funded by Swixx BioPharma. However, the authors state that the study of this clinical case was carried out independently from the company producing the asphotase alphaReferencesWhyte MP. Hypophosphatasia — aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016; 12(4):233–246. doi: 10.1038/nrendo.2016.Whyte MP. Hypophosphatasia — aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016; 12(4):233–246. doi: 10.1038/nrendo.2016.Whyte MP. Hypophosphatasia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. 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The authors declare that there are no conflicts of interest present.