Introduction: The clinical diagnosis of mild forms of hypophosphatasia [HPP], a rare genetic bone disease, is often made in adulthood, on the basis of persistently low serum levels of alkaline phosphatase [ALP], often coupled with signs of poor bone/teeth mineralization.
Case report: A 50-year-old male on treatment with vitamin D supplementation because of osteoporosis of lumbar spine (T-score 3.2) and femoral neck (T-score 2.4), was referred to our Center after radiological evidence of vertebral fractures, and the finding of persistently low ALP levels (27 to 29 U/L). He reported episodes of stiff neck, tingling, and upper limb paresthesias. Ultrasound revealed tendon calcifications, and lab tests confirmed persistently low levels of ALP and high levels of 25-OH vitamin D (86 ng/ml). A diagnosis of HPP was thus suspected and genetic tests were requested.
Objectives: Molecular analysis of the ALPL gene to confirm the clinical diagnosis of HPP, to be extended, as appropriate, to the patients relatives.
Methods: ALPL (NM_000478.4) sequencing was performed at our laboratory by Next Generation Sequencing [NGS] technology (MySeq Illumina).
Results: The coding sequence of exon 12 of our patient revealed the c.1328C>T (p.A443V) variant in heterozygous form a mutation already reported in HGMD Professional 2015.3 and in the ALPL gene mutation database (http://www.sesep.uvsq.fr/03_hypo_mutations.php), and associated to HPP. This confirmed the diagnosis of HPP (which required a substantial reduction of vitamin D supplementation). Upon this finding, we performed genetic analysis in our patients three daughters (respectively aged 8, 13 and 16 years), and the same genetic variant was found in the two youngest daughters. Their clinical history revealed appendicular fractures (1 and 2 respectively), and low serum levels of ALP for age (100 and 31 U/L respectively).
Conclusions: Genetic analysis is essential to confirm the diagnosis of mild forms of HPP. In this case, extending the analysis to our patients daughters allowed us to make an early diagnosis of mild HPP in two more subjects.
Disclosure: The authors declared no competing interests.