Bone Abstracts

Background: Hypophosphatasia (HPP) is a heterogeneous rare, inherited disorder of bone and mineral metabolism caused by different mutations in the ALPL gene encoding the isoenzyme, tissue-nonspecific alkaline phosphatase (TNAP). Prognosis is very poor in severe perinatal forms with most patients dying from pulmonary complications of their skeletal disease. TNAP, a ubiquitous enzyme, is mostly known for its role in bone mineralization. TNAP deficiency, however, may als...

Mutations of the ALPL-gene are closely related to hypophosphatasia (HPP), an inherited disorder of bone and mineral metabolism with clinically heterogeneous symptoms. To date 278 different mutations have been described, leading to reduction or completely loss of enzymatic activity of the tissue nonspecific alkaline phosphatase (TNAP).We present the case of a 6-year-old boy with clinical features and laboratory results consistent with infantile H...

Hypophosphatasia (HPP) is a rare disease characterized by low enzymatic activity of tissue-nonspecific alkaline phosphatase (TNSALP) resulting in an accumulation of its endogenous substrates like pyridoxal phosphate (PLP) and inorganic pyrophosphate (PPi). The ectoenzyme plays an important role during bone mineralization and might contribute to proper function of kidney and muscle. Neurological symptoms of HPP like seizures, anxiety disorders and depression provide ...

Objectives: Hypophosphatasia (HPP) is a rare metabolic disease caused by loss-of-function mutation(s) in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). HPP in infants is characterized by poor skeletal mineralization, respiratory compromise, and a high risk of mortality. We previously reported improved mineralization and respiratory function in 15 patients enrolled in this second study of asfotase alfa, a bone-targeted recombinant human TNSALP, in infants a...

Objectives: Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical presentation is highly heterogeneous with a remarkably wide-ranging severity. HPP affects patients of all age. Therefor diagnosis is often difficult and delayed. To improve the understanding of HPP in children and in order to shorten the diagnostic time span in th...

Objectives: Chronic non-bacterial osteomyelitis (CNO) is an inflammatory, non-bacterial disorder of the skeletal system of yet unknown etiology (ORPHA 324964). CNO predominantly affects the metaphyses of long bones, but lesions can occur at any sites of the skeleton. Patients present with local bone pain and inflammation and - to our experience - often suffer from functional impairment with significant disabilities of daily life. The objective of this study was to assess physi...

Background: Hypophosphatasia (HPP) is caused by inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase. Extracellular accumulation of inorganic pyrophosphate can lead to profound hypomineralization resulting in limb and chest deformity, respiratory complications and vitamin B6-dependent seizures in the severe forms of HPP. The natural history of HPP is poorly understood, but the perinatal and infantile forms are often considered lethal.<p class="...

Objectives: Asfotase alfa (AA), an enzyme replacement therapy, is the only approved treatment for pediatric-onset hypophosphatasia (HPP). We evaluated the safety profile of AA from the clinical trial program spanning pediatric and adult patients.Methods: Safety data were pooled from 4 open-label, multicenter studies in children aged ≤3 years (study 002/003 [NCT00744042/NCT01205152]; n=11) and ≤5 years (study 010-10 [NCT01176266]; <em...