Buyukyilmaz Gonul, Koca Serkan Bilge, Gören Refika, Uzdogan Andac, Adıguzel Keziban Toksoy, Uğurlu Aylin Kılınç, Yardimci Gonul, Kocaay Pınar, Tepe Derya, Boyraz Mehmet, Kilic Esra, Gürbüz Fatih
Department of Pediatric Endocrinology, Ankara Bilkent City Hospital, Ankara Yıldırım Beyazıt University Faculty of Medicine, Ankara, Türkiye.
Department of Pediatric Endocrinology, Kayseri City Education and Research Hospital, Kayseri, Türkiye.
Calcif Tissue Int. 2025 Aug 19;116(1):111. doi: 10.1007/s00223-025-01424-3.
Persistent low serum alkaline phosphatase (ALP) levels are crucial in identifying genetic disorders such as hypophosphatasia (HPP). This study investigates the causes of low ALP levels in children, aiming to evaluate the demographic and clinical characteristics of those diagnosed with HPP.We evaluated 2243 children and adolescents, ranging from 0 to 19 years old between September 2019 and July 2024, who exhibited at least two ALP levels below the age- and gender-specific lower limit.In the patient group, 95.4% (2140 patients) exhibited transient low ALP levels, while 4.6% (103 patients) showed persistently low levels. In the persistent group, eleven additional medical conditions were identified, excluding HPP, with calorie depletion (anorexia, malnutrition) being the most common cause. The study identified 16 HPP patients (10 females, 6 males) with high phenotypic variability even within the same variants, comprising 0.71% of the whole group. Genetic testing identified 13 pathogenic/likely pathogenic ALPL gene variants (10 heterozygous, 3 homozygous), two of which were novel. Among HPP patients, 56.2% presented with HPP-related symptoms, most commonly short stature. We found a significant negative correlation between total ALP and serum pyridoxal phosphate (PLP) levels (Rho = - 0.55, p = 0.039), but no correlation with urine phosphoethanolamine.Persistently low ALP levels are a vital clinical indicator for a wide range of disorders, especially HPP. This study expands the phenotypic and genotypic profiles of HPP while improving our understanding of the disease in children. Increasing disease awareness, particularly for milder forms, is essential to avoid delayed diagnosis.
持续低血清碱性磷酸酶（ALP）水平对于识别诸如低磷酸酯酶症（HPP）等遗传性疾病至关重要。本研究调查儿童低ALP水平的原因，旨在评估诊断为HPP的儿童的人口统计学和临床特征。我们评估了2019年9月至2024年7月期间年龄在0至19岁之间的2243名儿童和青少年，他们至少有两次ALP水平低于年龄和性别特异性下限。在患者组中，95.4%（2140例患者）表现为短暂性低ALP水平，而4.6%（103例患者）表现为持续性低水平。在持续性低水平组中，除HPP外还确定了另外11种疾病情况，热量消耗（厌食、营养不良）是最常见的原因。该研究确定了16例HPP患者（10名女性，6名男性），即使在相同变异类型中也具有高度的表型变异性，占整个研究组的0.71%。基因检测确定了13种致病/可能致病的ALPL基因变异（10种杂合子，3种纯合子），其中两种是新发现的。在HPP患者中，56.2%出现了与HPP相关的症状，最常见的是身材矮小。我们发现总ALP与血清磷酸吡哆醛（PLP）水平之间存在显著负相关（Rho = -0.55，p = 0.039），但与尿磷酸乙醇胺无相关性。持续低ALP水平是多种疾病尤其是HPP的重要临床指标。本研究扩展了HPP的表型和基因型谱，同时增进了我们对儿童期该疾病的理解。提高对该疾病的认识，特别是对较轻形式的认识，对于避免延迟诊断至关重要。
