Hypophosphatasia (HPP) is an inherited metabolic condition caused by pathogenic mutations in the ALPL gene. This leads to deficiency of tissue non-specific alkaline phosphatase (TNSALP), resulting in decreased mineralization of the bones and/or teeth and multi-systemic complications. Inheritance may be autosomal dominant or recessive, and the phenotypic spectrum, including age of onset, varies widely. We present four families demonstrating both modes of inheritance of HPP and phenotypic variability and discuss the resultant challenges in disease management, genetic counseling, and risk assessment. Failure to consider different modes of inheritance in a family with HPP may lead to an inaccurate risk assessment upon which medical and reproductive decisions may be made. We highlight the essential role of high-quality genetic counseling and meaningful biochemical and molecular testing strategies in the evaluation and management of families with HPP.

低磷血症（HPP）是由ALPL中的致病性突变引起的遗传性代谢病基因。这导致组织非特异性碱性磷酸酶（TNSALP）的缺乏，导致骨骼和/或牙齿的矿化减少以及多系统并发症。遗传可能是常染色体显性遗传或隐性遗传，并且表型谱（包括发病年龄）差异很大。我们介绍了四个家族，展示了HPP的遗传模式和表型变异性，并讨论了在疾病管理，遗传咨询和风险评估中所面临的挑战。如果不考虑HPP家庭的不同遗传方式，可能会导致风险评估不准确，从而无法做出医疗和生殖决策。我们强调了高质量的遗传咨询以及有意义的生化和分子检测策略在HPP家庭评估和管理中的重要作用。