Endocrine Abstracts

Introduction: Hypophosphatasia (HPP) is a rare genetic disease of very variable severity (from letal to mild). HPP results from APL gene mutations, which lead to a deficiency of tissue-nonspecifc alcaline phosphatase (TNAP), and accumulation of inorganic pyrophosphate, a potent inhibitor of mineralization that is also a natural substrate of TNAP in the extracelular space. HPP causes mineralization disorders including soft bones (rickets, osteomalacia, fractures) and defects in teeth. The broad-ranging expressivity that is largely explained by its autosomal recessive and autosomal dominant patterns of inheritance involving at least 300 different mutation (predominantly missense) in the TNSALP gen. Five principal subtypes of HPP are described: perinatal lethal, infantile, childhood, adult, odontohypophosphatasia and perinatal benign. We report a case of adult hypophosphatasia.

Case report: A 35 years old male patient with a history of loss of permanent teeth at a young age and pain bone (thigh, hip) was referred to our endocrine clinic to study after a recent family history sugestive of HPP.

Laboratory investigations revealed low serum alcaline phosphatase (ALP) (25 Ui/l; N 40–150), normal-low bone alcaline phophotase (6 μg/l N 6–30 μg/l), and normal levels of plasma and urine phosphoethanolamine (PEA), pyridoxal 5′-phosphate (PLP) and vitamine D.

Mutation analysis revelead a novel, heterozygous mutation within TNSALP gen (c.567_568 insT; p. Asn190stop)

Conclusions: As this condition is not well known by healthcare professionals, the time to diagnosis and initiation of adecuate treatment is postponed. HPP must be suspect when clinical o laboratory clues include premature loss of primary dentition, pseudofractures or recurrent poorly healing metatarsal stress fractures, a family history sugestive of HPP or low serum ALP activity. Recently has been aproved a fosfatase alfa, a first-in-class bone targeted human recobinant TNSALP replacement therapy with paediatric onset HPP. Bisphosphonates or too high doses of vitamine D are contraindicated.