Endocrine Abstracts

Hypophosphatasia (HPP) is a genetic condition affecting teeth and bones, identified by low levels of alkaline phosphatase (ALP) activity in the blood. This deficiency is caused by mutations in the ALPL gene, leading to an accumulation of substances that hinder bone mineralization. In adults, this can result in osteomalacia, frequent fractures, premature tooth loss, and arthralgia. We describe the case of a 38 year old Caucasian woman who was 24 weeks into her third pregnancy and was referred for a persistently low alkaline phosphatase enzyme (ALP). Her ALP has been low for over a decade (see graph), likely due to a genetic predisposition. She had a history of childhood fractures from low-impact trauma. She denies early loss of baby teeth. She reported myalgia during pregnancy with increased pain over the shoulder and pelvic girdles. Her first child, had metatarsal and metacarpal fractures from low- impact trauma and had lost dentition quite early in life. Her younger child, diagnosed with Tourette syndrome, had lost dentition and broken metatarsal and metacarpal bones from repetitive involuntary muscle twitching. Testing plasma copper level and serum selenium levels revealed normal results, however her plasma zinc levels were borderline and was replaced. A genetic testing revealed that she was a heterozygous for a likely pathogenic ALPL missense variant. Although the option for amniocentesis for prenatal diagnosis was discussed, it was decided against due to the advanced stage of pregnancy and the unlikelihood of changing pregnancy plans based on the results. This woman has been referred to the clinical geneticist for further evaluation. Currently, there is no approved treatment for adult HPP in the UK, but treatment is available, in the USA for pediatric cases using Asfotase alfa. This is a human recombinant tissue-nonspecific alkaline phosphatase that promotes mineralization of the skeleton. However, in spite of the limited treatment options, endocrinologists should have high suspicion of the clinical and biochemical features of adult HPP and refer them early to clinical geneticist for genetic counselling.