Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St Louis, MO; Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St Louis, MO.
Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.
J Pediatr. 2019 Jun;209:116-124.e4. doi: 10.1016/j.jpeds.2019.01.049. Epub 2019 Apr 9.
To report clinical characteristics and medical history data obtained retrospectively for a large cohort of pediatric patients with perinatal and infantile hypophosphatasia.
Medical records from academic medical centers known to diagnose and/or treat hypophosphatasia were reviewed. Patients born between 1970 and 2011 with hypophosphatasia and any of the following signs/symptoms at age <6 months were eligible: vitamin B6-dependent seizures, respiratory compromise, or rachitic chest deformity (NCT01419028). Patient demographics and characteristics, respiratory support requirements, invasive ventilator-free survival, and further complications of hypophosphatasia were followed for up to the first 5 years of life.
Forty-eight patients represented 12 study sites in 7 countries; 13 patients were alive, and 35 were dead (including 1 stillborn). Chest deformity, respiratory distress, respiratory failure (as conditioned by the eligibility criteria), failure to thrive, and elevated calcium levels were present in >70% of patients between birth and age 5 years. Vitamin B6-dependent seizures and respiratory distress and failure were associated significantly (P < .05) with the risk of early death. Serum alkaline phosphatase activity in all 41 patients tested (mean [SD]: 18.1 [15.4] U/L) was below the mean lower limit of normal of the reference ranges of the various laboratories (88.2 U/L). Among the 45 patients with relevant data, 29 had received respiratory support, of whom 26 had died at the time of data collection. The likelihood of invasive ventilator-free survival for this cohort decreased to 63% at 3 months, 54% at 6 months, 31% at 12 months, and 25% at 5 years.
Patients with perinatal or infantile hypophosphatasia and vitamin B6-dependent seizures, with or without significant respiratory distress or chest deformities, have high morbidity and mortality in the first 5 years of life.
ClinicalTrials.gov: NCT01419028.
报告回顾性收集的大量围产期和婴儿期低磷酸酶血症患儿的临床特征和病史数据。
对已知诊断和/或治疗低磷酸酶血症的学术医疗中心的病历进行了审查。出生于 1970 年至 2011 年间且在 6 个月龄前有以下任何体征/症状的低磷酸酶血症患儿符合纳入标准：维生素 B6 依赖性癫痫发作、呼吸窘迫或佝偻病性胸部畸形（NCT01419028）。对患者的人口统计学特征和临床表现、呼吸支持需求、无侵入性呼吸机存活以及低磷酸酶血症的进一步并发症进行了随访，最长可达 5 岁。
48 例患者代表了 7 个国家的 12 个研究地点；13 例患儿存活，35 例死亡（包括 1 例死产）。在出生至 5 岁之间，超过 70%的患儿存在胸部畸形、呼吸窘迫、呼吸衰竭（符合纳入标准）、生长不良和钙水平升高。维生素 B6 依赖性癫痫发作和呼吸窘迫和衰竭与早期死亡风险显著相关（P<.05）。所有 41 例接受检测的患者的血清碱性磷酸酶活性（平均[标准差]：18.1[15.4]U/L）均低于各实验室参考范围的平均下限（88.2 U/L）。在 45 例有相关数据的患者中，有 29 例接受了呼吸支持，其中 26 例在数据收集时已死亡。该队列的无侵入性呼吸机存活可能性在 3 个月时降至 63%，6 个月时降至 54%，12 个月时降至 31%，5 岁时降至 25%。
围产期或婴儿期低磷酸酶血症伴维生素 B6 依赖性癫痫发作、有或无明显呼吸窘迫或胸部畸形的患儿在生命的前 5 年有较高的发病率和死亡率。
ClinicalTrials.gov：NCT01419028。
