Searchable abstracts of presentations at key conferences on calcified tissues

ba0002p8 | (1) | ICCBH2013

Compound heterozygosity of two functional null mutations in the ALPL gene associated with deleterious neurological outcome in an infant with hypophosphatasia

Hofmann Christine , Liese Johannes , Girschick Hermann , Jakob Franz , Mentrup Birgit

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...

ba0003pp369 | Other diseases of bone and mineral metabolism | ECTS2014

A homozygous 20 bp intronic deletion in front of exon 8 of the ALPL-gene causes infantile hypophosphatasia: a functional characterization

Mentrup Birgit , Girschick Hermann , Jakob Franz , Hofmann Christine

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...

ba0003pp380 | Other diseases of bone and mineral metabolism | ECTS2014

TNSALP influences neurogenic differentiation by altering gene expression in SH-SY5Y cells

Graser Stephanie , Mentrup Birgit , Hofmann Christine , Schneider Doris , Jakob Franz

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 ...

ba0004oc18 | (1) | ICCBH2015

Improvement in bone manifestations and respiratory status in infants and young children with HPP treated with asfotase alfa: an update on the ENB-010-10 trial

Hofmann Christine , Rockman-Greenberg Cheryl , Harmatz Paul , Moseley Scott , Odrljin Tatjana , Liese Johannes

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...

ba0006oc16 | (1) | ICCBH2017

Pediatric hypophosphatasia – a retrospective single-center chart review of 50 children

Vogt Marius , Girschick Hermann Josef , Holl-Wieden Annette , Seefried Lothar , Jakob Franz , Hofmann Christine

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...

ba0006p184 | (1) | ICCBH2017

Physical activity and health-related quality of life in patients with chronic non-bacterial osteomyelitis – pilot and model project in a rare inflammatory bone disease

Nentwich Julia , Holl-Wieden Annette , Morbach Henner , Girschick Hermann Josef , Ruf Katharina , Hebestreit Helge , Hofmann Christine

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...

ba0003pp364 | Other diseases of bone and mineral metabolism | ECTS2014

Hypophosphatasia: a retrospective natural history study of the severe perinatal and infantile forms

Whyte Michael , Leung Edward , Wilcox William , Liese Johannes , Reeves Amy , Melian Agustin , Odrljin Tatjana , Zhang Hui , Hofmann Christine

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="...

ba0007p76 | (1) | ICCBH2019

Safety profile of asfotase alfa treatment of patients with hypophosphatasia: a pooled analysis

Whyte Michael P , Bishop Nick , Hasan Jawad , Hofmann Christine , Hogler Wolfgang , Rockman-Greenberg Cheryl , Sena Veruska , Zhou Shanggen , Kishnani Priya S

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...