Gabriele Haeusler's research while affiliated with Medical University of Vienna and other places

Publications (79)

Article
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Background: X‑linked hypophosphatemia (XLH) is characterized by increased serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphatemia and insufficient endogenous synthesis of calcitriol. Beside rickets, odonto‑ and osteomalacia, disproportionate short stature is seen in most affected individuals. Vitamin D analogs and phosphate su...
Article
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Background Gait deviations, lower limb pain and joint stiffness represent key symptoms in patients with X-linked hypophosphatemia (XLH, OMIM 307800), a rare disorder of mineral homeostasis. While the pathomechanism for rickets is well understood, the direct role of PHEX (Phosphate-regulating neutral endopeptidase) deficiency in non-rachitic feature...
Article
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Zusammenfassung Die Verwendung von geeigneten Referenzen zur Beurteilung von Körpermessdaten bei Kindern ist zentraler Bestandteil der kinderfachärztlichen Praxis. Es stehen seit Mai 2019 von der Fachgesellschaft empfohlene, großteils neu erstellte, österreichische Daten zur digitalen Anwendung zur Verfügung ( www.wachstum.at ). In diesem Beitrag w...
Article
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SP7/Osterix is a transcription factor critical for osteoblast maturation and bone formation. Homozygous loss-of-function mutations in SP7 cause osteogenesis imperfecta type XII, but neomorphic (gain-of-new-function) mutations of SP7 have not been reported in humans. Here we describe a de novo dominant neomorphic missense variant (c.926 C > G:p.S30...
Article
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Background: The ramifications of COVID-19 restrictions might accelerate the already rising proportion of children with overweight or obesity. Objectives: To assess the association between COVID-19 restrictions and changes in body mass index (BMI) and the proportion of children with overweight or obesity. Methods: Cohort study with baseline mea...
Article
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Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss‑of‑function mutations in the biomineralization associated alkaline phosphatase (ALPL) gene, encoding tissue-nonspecific alkaline phosphatase (TNSALP). Symptoms include skeletal hypomineralization and extra-skeletal manifestations such as pyridoxine (B6) responsive seizures due t...
Article
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Background: X-linked hypophosphatemia (XLH) is a rare genetic disorder characterized by lower limb deformity, gait and joint problems, and pain. Hence, quality of life is substantially impaired. This study aimed to assess lower limb deformity, specific radiographic changes, and gait deviations among adolescents and adults with XLH. Design: Data on...
Article
The heterogeneity of "rare bone disorders" can be explained by the number of molecules and regulatory pathways which are responsible for bone health and normal stature. In this article, the most important basic principles behind bone homeostasis from development to structure and regulation of the growing skeleton are summarized. The aim is to provi...
Poster
Acrodysostosis is a rare autosomal dominant disorder defined by skeletal abnormalities, multiple hormonal resistance and short stature. Based on the molecular findings, a new nomenclature has been proposed: iPPSD4 (ACRO1) caused by PRKAR1A alterations and iPPSD5 (ACRO2) involving PDE4D. Auxology data for both disorders are sparse and suggest a larg...
Article
Background: The acid-labile subunit (ALS) is a crucial factor in the tertiary complex. IGF-I and IGFBP-3 are routinely measured during the diagnostic work-up for growth hormone deficiency (GHD). The aim of the study is to evaluate the relevance of serum ALS as an additional biomarker in the diagnosis of GHD. Methods: Ninety-one children undergoi...
Article
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Zusammenfassung Osteoporose ist eine Erkrankung des Skelettapparats, die durch eine Beeinträchtigung der Knochenmikroarchitektur zu einer erhöhten Knochenbruchrate führt. Während Osteoporose im höheren Erwachsenenalter eine häufige Diagnose darstellt, wird der Osteoporose des Kindes- und Jugendalters erst seit relativ kurzer Zeit zunehmend Bedeutun...
Article
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Hyperphosphatemic conditions such as chronic kidney disease are associated with severe muscle wasting and impaired life quality. While regeneration of muscle tissue is known to be reliant on recruitment of myogenic progenitor cells, the effects of elevated phosphate loads on this process have not been investigated in detail so far. This study aims...
Article
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Objective Young women with Turner syndrome (TS) are known to be at risk for loss to medical follow‐up. Recent literature indicates that there are disparities regarding transition readiness between different chronic conditions. So far, studies in young women with TS investigating their transition readiness compared to youths with other chronic condi...
Article
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Background X-linked hypophosphatemia (XLH) represents the most common genetic form of rickets featuring profound hypophosphatemia with associated skeletal and non-skeletal manifestations. Early onset gait disturbances contribute strongly to the burden of disease. However, no study has comprehensively characterized naturally occurring gait deviation...
Article
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Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. Methods: BDAT bone ultrasound was perf...
Article
X-linked hypophosphatemia (XLH) caused by PHEX mutations results in elevated serum FGF23 levels, renal phosphate wasting and low 1,25-dihydroxyvitamin D. The glycophosphoprotein osteopontin, a potent inhibitor of mineralization normally degraded by PHEX, accumulates within the bone matrix. Conventional therapy consisting of supplementation with pho...
Article
Objectives To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. Methods BDAT bone ultrasound was perfo...
Article
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X‑linked hypophosphatemic rickets (XLH, OMIM #307800) is a rare genetic metabolic disorder caused by dysregulation of fibroblast-like growth factor 23 (FGF23) leading to profound reduction in renal phosphate reabsorption. Impaired growth, severe rickets and complex skeletal deformities are direct consequences of hypophosphatemia representing major...
Presentation
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Background: Sp7, also known as Osterix (Osx), is a zinc-finger transcription factor, essential for osteoblast differentiation and bone formation. While bone formation is absent in Osx knockout mice, human loss of function mutations lead to impaired bone formation and cause recessive osteogenesis imperfecta, type XII (OMIM 613849 ). Case: The 5-yea...
Article
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Objective Transfer from pediatric care into the adult health care system is known to be a vulnerable phase in the lives of youth with special health care needs (YSHCN). Recommendations from the literature favor assessment of transition readiness rather than simply pass over YSHCN from pediatric to adult-centered care by the age of 18. Nevertheless,...
Article
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Background In developed countries high socioeconomic status (SES) is associated with lower body mass index (BMI) and greater height compared with low SES. Aim To investigate differences in BMI/height in adolescent students from two different school types with divergent SES backgrounds. Methods A total of 4579 students (2313 female), aged 11–16 ye...
Poster
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Nach wie vor gibt es in Österreich – sowie im gesamten deutschsprachigen Raum - wenig kranheitsunspezifische Instrumente, um den Übergang von pädiatrischer Betreuung in die Erwachsenenmedizin zu begleiten. Der auf Englisch erprobte krankheitsunspezifische Fragebogen TRAQ 5.0 (Transition Assessment Readiness Questionnaire) zur Erhebung der Bereitsch...
Article
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Turner syndrome (TS) is a common genetic disorder in females with high incidence of ascending aortic dilatation and even dissection occurring as early as in the second decade. Known risk factors (RF) are bicuspid aortic valves (BAV), coarctation of the aorta (CoA), and arterial hypertension. Since 10% of dissections occur in patients without RF, an...
Article
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Background: Previous studies have shown that only a minority of patients with Turner syndrome (TS) have adequate medical care after transfer to adult care. Aim of this study: To assess the status of medical care and quality of life (QoL) in adult women diagnosed with TS and followed-up until transfer. To compare the subjective and objective view...
Poster
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Mit Transition wird im medizinischen Kontext die beabsichtigte und geplante Abgabe von Jugendlichen an die Erwachsenenmedizin bezeichnet.�Der Übergang in eine neue medizinische Betreuung wird häufig nicht zufriedenstellend vollzogen und geht Hand in Hand mit einer Verschlechterung der medizinischen Parameter, Vernachlässigen von Therapiemaßnahmen u...
Article
Background Context The process of linear growth is driven by axial elongation of both long bones and vertebral bodies and accomplished by enchondral ossification. Differences in regulation between the two skeletal sites are mirrored clinically by the age course in body proportions. Whereas growth plates in long bones can easily be discriminated, ve...
Chapter
Growth in mammals is a unique and fascinating process which takes place in the growth plates (GP) of long bones and vertebrae.
Article
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Turner syndrome (TS), although considered a rare disease, is the most common sex chromosome abnormality in women, with an incident of 1 in 2,500 female births. TS is characterized by distinctive physical features such as short stature, ovarian dysgenesis, an increased risk for heart and renal defects as well as a specific cognitive and psychosocial...
Article
Core areas in voluminous pieces of permanent cartilage are metabolically supplied via vascular canals (VCs). We studied cartilage corrosion and removal of matrix degradation products during the development of VCs in nose and rib cartilage of piglets. Conventional staining methods were used for glycosaminoglycans, immunohistochemistry was performed...
Article
Background: A female infant was admitted to hospital due to failure to thrive. She presented hypercalcemia (4.09 mmol/L, normal range: 2.2-2.65 mmol/L), high 25-hydroxyvitamin D (283 nmol/L, normal range: 75-250 nmol/L), 1,25-dihydroxyvitamin D in the upper normal range, and low parathyroid hormone. Vitamin D intoxication was suspected. The patien...
Article
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Objective: Seamless transition of endocrine patients from the paediatric to adult setting is still suboptimal, especially in patients with complex disorders, i.e., Small for Gestational Age, Turner or Prader-Willi Syndromes; Childhood Cancer Survivors, and those with Childhood Onset Growth Hormone Deficiency. Methods: An Expert Panel meeting com...
Article
Background: Disturbance of systemic phosphate homeostasis is often associated with musculoskeletal dysfunction. Multiple factors related to the underlying condition such as calcium levels and endocrine mechanisms are thought to contribute. Distinct effects of inorganic phosphate itself as well as its main regulator FGF23 by activation of similar pa...
Article
Background: The measurement of insulin-like growth factors (IGF-I) and insulin-like growth factor-binding protein (IGFBP-3) often serves as first-line testing in children with growth disorders. The role of acid-labile subunit (ALS) as a screening parameter for homozygous or heterozygous mutations of the ALS gene still has to be determined. Method...
Article
Background: BMI reference charts are widely used to diagnose overweight, obesity and underweight in children and adolescents. Aim: To provide up-to-date national reference values for Austria. Methods: A cross-sectional sample of over 14 500 children and adolescents (4-19 years) stratified by provinces according to age- and sex-specific populat...
Article
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Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are importa...
Article
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Alterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, par...
Article
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Context: Aromatase deficiency due to a CYP19A1 defect leads to fetoplacental inability to convert androgens into estrogens. Pregnant mothers experience virilization caused by excess nonaromatized fetal androgens entering the maternal circulation. Biochemical normalization is believed to take place shortly after delivery. Objective: We report pro...
Article
Background: Previous studies have demonstrated differences between national and the WHO reference curves in children older than 5 years. Moreover, reference curves for body proportions (sitting height, subischial leg length and their ratio) based on state-of-the-art statistics are not available. Aim: To develop reference curves for height and bo...
Article
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Introduction: Regulation of phosphate homeostasis is essential for mineralization and enchondral ossification. Fibroblast growth factor 23 (FGF23) and its obligatory co-receptor Klotho (KL) play a key role in this process by influencing both renal phosphate reabsorption and vitamin D metabolism. In disease, excessive action of FGF23 leads to hypop...
Article
Case report: A female patient with consanguineous parents presented with severe symptomatic hypocalcemia (1.62mmol/l) at the age of 4 months. Treatment with oral 1,25-(OH)2-vitamin D and calcium carbonate was started and serum calcium concentrations were stabilized at the lower end of the normal range. Subsequently she developed normally and had n...
Article
IGF-I and IGF-II are key regulators of growth and metabolism. Still, data about their expression and distribution within the growth plate in different animal models remain contradictory. Inferences drawn from rodent animal models can only be applied to human conditions to a limited extent as the rodent's growth plate never fuses. In this study, we...
Article
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The mechanism behind disabling muscle weakness in tumor-induced hypophosphatemic rickets is obscure. Histological investigation of growth plate tissue of patients with tumor-induced osteomalacia has so far not been reported. A mesenchymal tumor was detected in the left distal fibula by (68)Ga-DOTATOC in a 17-yr-old boy with adolescent onset of seve...
Article
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To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown. The study evaluates the impact of heterozygous expression of IGFALS mutations on phenotype based on data collected by the International ALS Consortium. Patient information...
Article
In this study we compared the expression of hormone receptors and markers of differentiation in growth plate chondrocytes (GPC) and articular chondrocytes (AC) under different culture conditions by real-time PCR and immunofluorescence. After one week of monolayer culture, porcine GPC and AC of 6-8-week-old piglets were either seeded in alginate bea...
Article
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Der „Carney-Komplex“ (CRC, OMIM 160980) ist ein 1981 von J. A. Carney erstmals beschriebenes, sehr seltenes Neoplasiesyndrom, das häufig mit einem Glukokortikoidexzess einhergeht. In den meisten Fällen liegt eine Mutation des PRKAR1A-Gens vor, welches für eine Untereinheit der Proteinkinase A kodiert und cAMP-mediierte Signalkaskaden reguliert. Mut...
Article
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Primary GH insensitivity (GHI) or Laron syndrome, caused by mutations of the GH receptor (GHR) gene, has a clinical phenotype of postnatal growth failure associated with normal elevated serum concentrations of GH and low serum levels of IGF-I. We investigated the clinical and biochemical implications of molecular defects in the GHR gene in an Austr...
Article
Primary IGF deficiency (IGFD) describes the condition in which serum concentrations of IGF-I are low in the face of normal to elevated GH production. Because IGF-I, which circulates as part of a ternary complex with IGF binding protein (IGFBP)-3 and acid-labile subunit (ALS), mediates the growth-promoting effects of GH, IGFD is associated with seve...
Article
Numerous studies have focused on the expression, regulation, and biological significance of matrix metalloproteinases (MMPs) in the growth plate. Findings in mouse knockout models and in vitro data from various species indicate that MMPs not only degrade extracellular matrix components but may regulate the activity of local growth factors. In this...
Article
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SHOX mutations causing haploinsufficiency were reported in Leri-Weill dyschondrosteosis (LWD), which is characterized by mesomelic short stature and Madelung deformity of the wrists. The aim of this study was to determine the prevalence of SHOX mutations in LWD and to investigate the degree of growth failure in relation to mutation, sex, age of men...
Article
The growth plate is a highly specialized layer of cartilage where chondrocytes proliferate and differentiate in order to bring forth longitudinal bone growth. Interaction of cells with the extracellular matrix significantly influences differentiation and growth. These processes involve integrin as well as nonintegrin cell surface receptors, like an...
Article
Interaction of chondrocytes with the surrounding matrix significantly influences differentiation and growth. These processes involve cell surface proteins, particularly integrins. The aim of this study was to compare the expression of integrins (alpha1, alpha2, alpha3, alpha5, alpha6, alphav, beta1, beta3, and beta5 subunits) together with matching...
Article
To localize estrogen receptor-alpha (ER-alpha) and estrogen receptor-beta (ER-beta) within the growth plate and adjacent bony tissue of children in the prepubertal and pubertal age period. Tissue was taken during orthopedic surgery (epiphysiodesis) for correction of congenital or traumatic leg length difference in 2 prepubertal females and 2 adoles...
Article
The presence of Y-chromosomal sequences in the cells of patients with Turner-Syndrome (TS) is a risk factor for the development of gonadal tumors. Therefore and since demonstration of Y-material usually results in prophylactic gonadectomy optimal sensitivity and specifity of the diagnosis have to be attempted. We wanted to evaluate the diagnostic p...
Article
This article summarizes the published data on final height after growth-promoting therapy in Turner syndrome. Using growth hormone (GH) doses ranging between 0.5 and 1.2 IU/kg/week, final height after therapy is improved by 1.5-9.3 cm [final height after therapy vs. projected adult height (PAH)] within various studies. There is no obvious GH dose-r...
Article
This article summarizes the published data on final height after growth-promoting therapy in Turner syndrome. Using growth hormone (GH) doses ranging between 0.5 and 1.2 IU/kg/week, final height after therapy is improved by 1.5-9.3 cm [final height after therapy vs. projected adult height (PAH)] within various studies. There is no obvious GH dose-r...
Article
In 41 girls with Turner syndrome, the growth hormone (GH) peak values during stimulation tests and parameters of spontaneous nocturnal GH secretion were studied and compared with respect to different karyotypes, short-term growth response to GH therapy, and final height. 22.0% of the girls tested had a subnormal (peak < 11 ng/ml) and 9.7% a patholo...
Article
Two boys are presented with the clinical features of cerebral gigantism and chromosomal variants which have not been described so far in this syndrome. In the first boy a de novo pericentric inversion of chromosome Y was found, the karyotypes of all other investigated family members were normal. The patient had an obstructive hypertrophic cardiomyo...
Article
A potential relation was evaluated between nocturnal urinary growth hormone (GH) excretion as a parameter for integrated GH secretion and the course of blood glucose (BG) levels during night and morning hours. Twelve diabetic children aged 11.6 +/- 2.0 years (mean +/- SD), with diabetes duration 4.4 +/- 1.6 years, took part in the study. Urine for...
Article
A 3-year-old Libyan boy with the XXXXY syndrome is described. MRI examination of the brain showed hypoplasia of the corpus callosum. He had growth retardation and endocrine studies demonstrated growth hormone (GH) deficiency. Dermatoglyphic pattern was different from previous reports. At histological examination of the undescended testes, Leydig ce...
Article
The effect of GH administration on various metabolic parameters and on growth and bone age development was studied in patients with Turner's syndrome. Patients were treated with daily s.c. GH (20 IU/m2/week) and ethinyloestradiol p.o. (100 ng/kg/day) during the first year and with additional oxandrolone (0.125 mg/kg/day) during the second year. The...

Citations

... In most cases, these neomorphs and the ensuing altered expression of genes predisposes to malignancies (26)(27)(28). Furthermore, neomorphic germline mutations cause osteogenesis imperfecta in SP7 (29), anemia in EKLF (30), and arteriopathy in NOTCH3 (31), to mention a few. However, we are not aware of human diseases caused by the multimorphic combination of hypermorphic, hypomorphic, and neomorphic activity as displayed by IRF4 T95R . ...
... In addition, according to 30 million FitBit users, there was a significant decline in step counts (week ending on March 22, 2020 compared to same week in 2019) (35). Together, these changes may have long term adverse consequences on chronic disease risk and health, and could subsequently impact the health of the population in the future (25). In addition to changes in PA, there were also changes in dietary patterns during the COVID-19 pandemic (33). ...
... Die komplexen Veränderungen der Beinachse haben krankheitsspezifische Gangveränderungen zur Folge [3][4][5][6] und wirken sich auf die Lebensqualität von PatientInnen mit XLH aus [7]. ...
... More data regarding the impact of achondroplasia on different domains of HRQoL, age-specific surgical burden, and the relationship between height and specific medical complications is expected from the LIAISE study, a multinational, observational, retrospective study with a cross-sectional patient-reported outcome component. Preliminary data of LIAISE showed reduced physical and psychosocial domain scores across several questionnaires and a high surgical burden in individuals with achondroplasia [23,25]. The data also suggested a positive correlation between HRQoL and height Z-score [25]. ...
... In addition to disproportionate short stature, medical complications may impact on the HRQoL of individuals with achondroplasia. Complications may result in frequent surgeries such as ear-nose-throat (mainly in children) and orthopedic procedures [4,23], chronic pain, reduced work participation (e.g. due to symptomatic spinal stenosis in adults) and, in some cases, reduced life expectancy [19,24]. ...
... Several potential alternatives to IGF-1 have been proposed but despite clinical correlation with GH-related diseases in those markers, none of them got established in clinical diagnostics [29][30][31][32][33]. So there is still the need for a more accurate biomarker, which can be used for diagnosis as well as assessment of disease activity [34]. ...
... On the other hand, in vitro studies on a C2C12 mouse model have shown that the elevation of phosphate levels impairs myoblast differentiation, significantly decreasing myoblast differentiation gene expression [64,65]. Moreover, it has been shown that hyperphosphatemia promotes cellular senescence of culture myoblasts and reduces their proliferative activity [66]. ...
... These individuals therefore do not receive the recommended screening and care for disease-associated comorbidities, leading to poor health outcomes (25). Notably, adequate medical care following the transition occurs in only 3.5% of individuals with TS (172). ...
... MRI could be helpful to determine closure of growth plates in adolescents and to monitor changes in bone quality (43,44). Additional tools such as EOS 2D/3D imaging and Gait lab could be useful to determine changes in bone quality and bone deformity, especially in older children (4,45). ...