Petković Ramadža Danijela, Žigman Tamara, Čavka Mislav, Barić Ivo
Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia.
School of Medicine, University of Zagreb, Zagreb, Croatia.
Front Endocrinol (Lausanne). 2025 Jun 18;16:1587807. doi: 10.3389/fendo.2025.1587807. eCollection 2025.
Hypophosphatasia (HPP) is a rare, inherited metabolic disorder due to a deficiency of tissue-nonspecific alkaline phosphatase, characterized by defective bone and teeth mineralization with consequent problems, including respiratory failure in severe types of HPP. Severe patients exhibit other disease-related manifestations, including neurological manifestations, which make HPP complex and difficult to manage. Enzyme replacement therapy with asfotase alfa is a disease-specific treatment for skeletal manifestations in pediatric patients. We present a patient with perinatal HPP who had a severe clinical course with respiratory insufficiency during infancy requiring a higher dose of asfotase alfa than recommended (12 mg/kg/week). After improvement of respiratory function and outgrowing the higher dose, the patient was maintained on the standard dose (6 mg/kg/week) from the age of 3 years. At 6 years of age, unexplained clinical and radiographic deterioration occurred while laboratory parameters remained normal. Following a traumatic humerus fracture that occurred after several months, asfotase alfa was increased to 10 mg/kg/week. Remarkable clinical improvement was observed and the patient regained the ability to walk unassisted 3 months after the dose correction. The rickets severity score changed from 10 to 3.5 within 14 months. No side effects from the higher drug dose have been noticed. The remaining challenge in this patient was a neurodevelopmental disorder. In conclusion, the standard dose of asfotase alfa was not sufficient to treat the skeletal manifestations of HPP in our patient, indicating that some perinatal HPP patients should be treated with higher doses to reach treatment goals. Although bone disease and patient outcomes have been improved with tailored drug doses, neurological manifestations of HPP remain challenging.
低磷性骨软化症（HPP）是一种罕见的遗传性代谢紊乱疾病，由于组织非特异性碱性磷酸酶缺乏所致，其特征为骨骼和牙齿矿化缺陷，进而引发一系列问题，包括严重型HPP的呼吸衰竭。重症患者还会出现其他与疾病相关的表现，包括神经学表现，这使得HPP病情复杂且难以管理。阿法骨化醇酶替代疗法是针对儿科患者骨骼表现的一种疾病特异性治疗方法。我们报告了一名围产期HPP患者，其在婴儿期临床过程严重，伴有呼吸功能不全，需要比推荐剂量（12mg/kg/周）更高剂量的阿法骨化醇酶。在呼吸功能改善且不再需要高剂量治疗后，该患者从3岁起维持标准剂量（6mg/kg/周）。6岁时，尽管实验室参数仍正常，但出现了不明原因的临床和影像学恶化。在数月后发生肱骨创伤性骨折后，阿法骨化醇酶剂量增加至10mg/kg/周。观察到显著的临床改善，剂量校正3个月后患者恢复了独立行走能力。佝偻病严重程度评分在14个月内从10降至3.5。未发现高剂量药物有副作用。该患者面临的剩余挑战是神经发育障碍。总之，阿法骨化醇酶的标准剂量不足以治疗我们患者的HPP骨骼表现，这表明一些围产期HPP患者应使用更高剂量进行治疗以达到治疗目标。尽管通过调整药物剂量改善了骨病和患者预后，但HPP的神经学表现仍然具有挑战性。
