A rare mutation in hypophosphatasia: a case report of adult form and review of the literature

• Authors: Francisco Galeano-Valle, Hospital General Universitario Gregorio Marañón; Jaime Vengoechea Barrios, Emory University; Rodolfo Galindo, Emory University
• Journal Title: ARCHIVES OF ENDOCRINOLOGY METABOLISM
• Volume: Volume 63, Number 1
• Publisher: SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA | 2019-01-01, Pages 89-93
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.20945/2359-3997000000108
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Endocrinology & Metabolism; ATYPICAL FEMORAL FRACTURES; DISEASE; NOSOLOGY; BURDEN

Abstract

Hypophosphatasia is a rare inborn error of metabolism characterized by low serum alkaline phosphatase activity due to loss-of-function mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Extracellular accumulation of TNSALP substrates leads to dento-osseous and arthritic complications featuring tooth loss, rickets or osteomalacia, and calcific arthopathies. Mild hypophosphatasia usually has autosomal dominant inheritance, severe cases are either autosomal recessive or due to a dominant negative effect. Clinical manifestations of hypophosphatasia are extremely variable, ranging from life threatening to asymptomatic clinical presentations. The clinical presentation of the adult-onset hypophosphatasia is highly variable. Fractures, joint complications of chondrocalcinosis, calcifying polyarthritis and multiple pains may reveal minor forms of the disease in adults. It is important to recognize the disease to provide the best supportive treatment and to prevent the use of anti-resorption drugs in these patients. Bone-targeted enzyme-replacement therapy (asfotase alfa) was approved in 2015 to treat pediatric-onset hypophosphatasia. We present a case of a 41-year-old male diagnosed with adult form of hypophosphatasia with a rare ALPL mutation that has been previously described only once and review the literature on the adult form of the disease and its genetic mechanism.