Case Report
Multigenerational case examples of hypophosphatasia: Challenges in genetic counseling and disease management

https://doi.org/10.1016/j.ymgmr.2020.100661Get rights and content
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Abstract

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.

Keywords

Hypophosphatasia
Alkaline phosphatase
Family history
Genetic counseling
ALPL gene
Dominant inheritance
Recessive inheritance

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