Endocrine Abstracts

A 28 year old female was referred to endocrinology after routine bloods during first trimester of pregnancy demonstrated a low alkaline phosphatase (ALP) of 14U/l (range 30-130U/l). Calcium, phosphate and vitamin D were normal. There is no past medical history, no fragility fractures, no dental concerns and height was normal (157.5cm). Her only family history was her mother lost her teeth prematurely. Biochemical testing showed a raised copper level of 26.0µmol/l (range 11-25µmol/l) which may be pregnancy related. PLP (pyridoxal 5′-phosphate) was raised at 423.65nmol/l (range 20-140nmol/l) and PLP:PA ratio significantly raised at 15.13. Genetic analysis confirmed hypophosphatasia (HPP) with a heterozygous pathogenic mutation in ALPL gene variant c.382G>A p. (Val128Met). HPP is a rare genetic disorder characterised by defective mineralisation of bones and teeth due to ALP deficiency. The ALPL gene encodes the tissue non-specific isoenzyme of ALP (TNSALP) and gene mutations reduces activity of ALP. This leads to extracellular accumulation of PLP which further reduces skeletal mineralisation. The features are highly variable in their expression and range from a perinatal lethal form, to presenting in child or adulthood. It can cause fragility fractures, joint pain and dental issues known as odontohypophosphatasia. Management includes genetic counselling, analgesia and enzyme replacement therapy with asfotase alfa (Strensiq). This replaces the missing enzyme and promotes bone mineralisation. It is not widely available and is reserved for those with severe disease, or who develop HPP at a younger age. Strensiq has been shown to reduce the PLP:PA ratio and improve functional outcomes. In summary, this is an unusual case of HPP presenting in the first trimester of pregnancy in an asymptomatic individual but who may be at risk of developing odontohypophosphatasia in the future. This patient had an uncomplicated pregnancy and delivered a healthy baby who does not have HPP.