Childhood hypophosphatasia: to treat or not to treat
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Childhood hypophosphatasia: to treat or not to treat Eric T. Rush1,2
Abstract Background: Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from dysfunction of the tissue non-specific alkaline phosphatase enzyme. Its manifestations are extremely variable, ranging from early lethality to disease limited to the dentition. The disease is life-threatening when manifesting within the first six months of life, excepting the extremely rare benign perinatal hypophosphatasia. Childhood hypophosphatasia, defined as onset of symptoms between six months and eighteen years, can manifest as rickets, pain, decreased mobility, deficits of growth, and fractures. Historical treatment has generally involved a combination of dietary and rehabilitative interventions. Main document: Asfotase alfa (Strensiq™), is a first-in-class bone-targeted recombinant tissue nonspecific alkaline phosphatase which has shown significant improvements in morbidity and mortality in patients with perinatal and infantile hypophosphatasia. Subsequent research has also shown improvements in morbidity for patients with childhood hypophosphatasia as measured by improvement in rickets, growth, strength, mobility, and quality of life. This enzyme replacement therapy has generally been well-tolerated, with most adverse reactions being mild-to-moderate in nature. The author shares their approach to decisions on commencement of ERT based from experience of managing approximately fifteen patients across the age spectrum. This approach focuses on assessing the severity of five key manifestations of childhood HPP: decreased mobility, pain, rickets, deficits of growth, and fractures. Keywords: Hypophosphatasia, Alkaline phosphatase, Rare bone disease, Rickets, Brittle bone disease, Asfotase alfa, Enzyme replacement therapy
Background Hypophosphatasia (HPP) is an inborn error of metabolism that is caused by mutations of the ALPL gene, which encodes the tissue nonspecific alkaline phosphatase (TNSALP) isoenzyme [1]. HPP is a rare and variable condition and presentation can occur at any time in the lifespan [2]. The incidence is not completely understood, but the incidence of 1 in 100,000 for severe disease based off of a population in Ontario [3] has been frequently cited. Estimates for less severe forms of hypophosphatasia have been made utilizing molecular data and have suggested an incidence of 1 in 6370 [4]. HPP has been divided into a number of subtypes based on clinical presentation and timing of onset and include perinatal-, infantile-, childhood-, Correspondence: [email protected] 1 Division of Clinical Genetics, Department of Pediatrics, Children’s Mercy Kansas City, 2401 Gillham Road, Kansas City, MO 64108, USA 2 Division of Endocrinology, Metabolism, and Genetics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
and adult-onset. An additional category of odontohypophosphatasia is used for disease that limited to the teeth. HPP has classically been described as an autosom
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