Clinical profiles of treated and untreated adults with hypophosphatasia in the Global HPP Registry

Abstract

Background The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stage of life. The age at which a patient’s symptoms are reported can impact access to targeted treatment with enzyme replacement therapy (asfotase alfa), as this treatment is indicated for patients with pediatric-onset HPP in most countries. As such, many patients reported to have adult-onset HPP typically do not receive treatment. Comparison of the disease in treated and untreated adult patients is confounded by the approved indication. To avoid this confounding factor, a comparison between baseline disease manifestations prominent among treated versus untreated adult patients was limited to those with pediatric-onset HPP using data collected from the Global HPP Registry. The hypothesis was that treated adults will have a greater disease burden at baseline than untreated adults. The analysis of disease manifestations in adults with adult-onset HPP was conducted separately. Results A total of 398 adults with HPP were included; 213 with pediatric-onset (114 treated, 99 untreated) and 141 with adult-onset HPP (2 treated and 139 untreated). The treated, pediatric-onset patients were more likely to have a history of pain (prevalence ratio [PR]: 1.3, 95% confidence interval [CI] 1.1, 1.4), skeletal (PR: 1.3, 95% CI 1.1, 1.6), constitutional/metabolic (PR: 1.7, 95% CI 1.3, 2.0), muscular (PR: 1.8, 95% CI 1.4, 2.1) and neurological (PR: 1.7, 95% CI 1.1, 2.3) manifestations of HPP, and also had poorer measures for health-related quality of life, pain, and disability compared with untreated pediatric-onset patients. In patients with adult-onset HPP, the most frequent signs and symptoms were chronic bone pain (52.5%), dental manifestations (42.6%), fatigue (23.4%), recurrent fractures or pseudofractures (22.0%), and generalized body pain (22.0%). Conclusions Along with the more classical skeletal signs and symptoms, pain, muscular, and constitutional/metabolic manifestations are common in adults with HPP, regardless of age of disease onset, highlighting a full spectrum of HPP manifestations.

Praxisrelevante Aspekte zur biochemischen und molekulargenetischen Diagnostik bei seltenen Knochenerkrankungen – vom Netzwerk Seltene Osteopathien (NetsOs*)

“…Die HPP ist eine Multisystemerkrankung mit einem breiten Spektrum an Schweregraden. Die klinisch schwersten, lebensbedrohlichen Fälle (perinatale und infantile HPP) sind fast ausschließlich rezessiv vererbt, während das moderat bis milde Spektrum der Erkrankung (childhood, adult, odonto) meist dominant vererbt ist [34]. Individuelle Komplikationen können aber auch zu schwerwiegenden Verläufen führen.…”

Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia

“…According to the data from the global HPP Registry, over half of patients reported experiencing chronic bone pain (52.5%) [ 18 ]. Joint pain associated with arthropathy and chondrocalcinosis are also common [ 17 , 19 ].…”

“…Joint pain associated with arthropathy and chondrocalcinosis are also common [ 17 , 19 ]. Dental complications such as tooth pain, periodontitis, and dental caries can occur [ [17] , [18] , [19] ]. The excess presence of pyrophosphate (PPi) can cause various complications, including calcium pyrophosphate dihydrate (CPPD) deposition (CPPD arthropathy), PPi arthropathy, or pseudogout.…”

“…These criteria are also characteristic of atypical femur fracture associated with prolonged anti-resorptive use [ 24 , 25 ]. In adult HPP patients, approximately 20%–50% have experienced at least 1 fracture, and many of them have had multiple events [ 18 , 19 , 24 ]. Atypical fracture or HPP-related fracture occurs in up to 20% of adult HPP patients [ 24 , 26 , 27 ].…”

Systemic Effects of Hypophosphatasia. Characterization of Two Novel Variants in the Alpl Gene

“…The clinical features of this disease range from completely asymptomatic patients to complete absence of bone mineralization and fetal death 15 . The disease conditions can affect different organs and systems including skeletal 15,16 , muscular 17 , dental 18 , neurological 19 , respiratory 15 , renal 20 and articular 21 due to accumulation of their substrates (Fig. 1C).…”