Strandbech Olivia Sarah, Lund Allan, Ostergaard Elsebet
Department of Clinical Genetics Copenhagen University Hospital Copenhagen Denmark.
Centre Inherited Metabolic Diseases, Departments of Clinical Genetics and Pediatrics Copenhagen University Hospital Copenhagen Denmark.
JIMD Rep. 2021 Feb 3;59(1):10-15. doi: 10.1002/jmd2.12198. eCollection 2021 May.
Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of alkaline phosphatase, causing defective mineralization of bones and teeth. The symptoms vary from no symptoms to stillbirth or skeletal manifestations. Since 2015, asfotase alfa, an enzyme replacement treatment, has been approved for pediatric use in some jurisdictions. We describe the clinical outcome of asfotase alfa therapy in an adolescent patient with childhood HPP. The patient was diagnosed with HPP at 13 months. She had a history of hypertonia and failure to thrive from age 3 months. During childhood the patient experienced chronic skeletal pain, requiring daily use of analgesics and school absences. Her plasma pyridoxal-5-phosphate was elevated at >2500 mmol/L, phosphoethanolamine at 11 μM, and ALP decreased at 25 U/L. On the visual analog scale (VAS), a scale used to determine pain intensity, she stated an average of 7 (maximum 10) at age 13. She had no abnormalities on radiography. At age 13 the patient was started on asfotase alfa 1 mg/kg given subcutaneously 6 times weekly. Three months after treatment the patient had a decreased P-pyridoxal-5-phosphate level of 41 mmol/L, used fewer analgesics, and a lower average VAS-score. At every follow-up, she continued to exhibit improved biochemical values, along with lower VAS-scores. In conclusion, asfotase alfa significantly improved the patient's quality of life. This case suggests an association between children with HPP without radiographic abnormalities, but a debilitating pain phenotype, and a significant pain reduction on enzyme replacement therapy. Thus, this therapy should be considered in such patients.
低磷酸酯酶症（HPP）是一种罕见的遗传性代谢紊乱疾病，其特征是碱性磷酸酶活性不足，导致骨骼和牙齿矿化缺陷。症状从无症状到死产或骨骼表现不等。自2015年以来，阿法骨化醇酶，一种酶替代疗法，已在一些司法管辖区被批准用于儿科。我们描述了阿法骨化醇酶治疗一名患有儿童期HPP的青少年患者的临床结果。该患者在13个月时被诊断为HPP。她从3个月大起就有肌张力亢进和发育不良的病史。在儿童期，该患者经历了慢性骨骼疼痛，需要每天使用止痛药并缺课。她的血浆磷酸吡哆醛-5-磷酸升高至>2500 mmol/L，磷酸乙醇胺为11 μM，碱性磷酸酶降至25 U/L。在用于确定疼痛强度的视觉模拟量表（VAS）上，她在13岁时表示平均疼痛评分为7分（满分10分）。她的X光检查没有异常。13岁时，该患者开始皮下注射阿法骨化醇酶，剂量为1 mg/kg，每周6次。治疗三个月后，患者的磷酸吡哆醛-5-磷酸水平降至41 mmol/L，使用的止痛药减少，平均VAS评分降低。在每次随访中，她的生化指标持续改善，VAS评分也更低。总之，阿法骨化醇酶显著改善了患者的生活质量。该病例表明，患有HPP但无影像学异常但有使人衰弱的疼痛表型的儿童与酶替代疗法能显著减轻疼痛之间存在关联。因此，这类患者应考虑采用这种疗法。
