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Pediatric Endocrinology Reviews (PER) is the most respected international peer reviewed journal in Pediatric Diabetes, Nutrition Metabolism and Genetics. Hypothyriodism, Hyperthyriodism, Glycemic Management for Children with Diabetes Glucose Monitoring Adrenal Insufficiency Turner Syndrome Late Adolescence Klinefelter Syndrome Children with Short Stature and Growth Failure: Heightism Type 1 Diabetes in Children Growth Hormone Treatment for GHD Insulin-like Growth Factor-I Growth Hormone Deficiency SGA Children with Short Stature Receiving GH Treatment Hypothalamic Obesity Adolescent Gynecomastia Hematospermia in Adolescents Gain-of-Function CDKN1C Mutations Craniopharyngioma Succinate-Dehydrogenase Deficient Paragangliomas/Pheochromocytomas Adrenal Steroidogenesis: Impact on Gonadal Function Focal Congenital Hyperinsulinism (CHI)  Longevity Hormone Klotho Pediatric Congenital Hypothyroid Lysosomal Storage Diseases Juvenile NCL (CLN3 Disease) GM1 and GM2 Gangliosidoses Types A and B Niemann-Pick Disease CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis) Krabbe Disease Fucosidosis Nuclear Factor Kappa B (NF-κB) in Growth Plate Chondrogenesis Persistent Müllerian Duct Syndrome LHX4 Gene Alterations Stunted Growth 45,X/46,XY Gonadal Dysgenesis Thyroid Hemiagenesis Nutrimetabolomics and Adipocitokines Chromosomal Microarray Analysis (CMA) Chromosomal microarray, Copy Number Variant (CNV), Prenatal, Amniocentesis, Comparative genomic hybridization, SNP array, Diagnosis, Clinical Abreviations: aCGH – array-based comparative genomic hybridization, ASD – autism spectrum disorder, BAC – bacterial artificial chromosome, CHD – congenital heart disease, CMA – chromosomal microarray analysis, CNV – copy number variant, CVS – chorionic villus sampling, DD – developmental delay, DNA – deoxyribonucleic acid, FISH – fluorescent in situ hybridization, GABA - gammaaminobutyric acid, ID – intellectual disability, LOH – loss of heterozygosity, NGS – next generation sequencing, NIPT – noninvasive prenatal testing, NOS – not otherwise specified, PGD - preimplantation genetic diagnosis, SNP – single nucleotide polymorphism, VUS – variant of unclear clinical significance Central precocious puberty, Traumatic brain injury, Pathophysiology Nephrolithiasis, Nephrocalcinosis, Hypercalciuria, Hyperoxaluria, Hypouricemia, Cystinuria, Genetics 

Vol. 15 Supplement 1

Dec 2017

 

The successful way of BKMF - Self-Help meets science

 

Ruzena Klingebiel, Karl-Heinz Klingebiel

 

Abstract

Advocacy, information and psychosocial support have been the key aims of the German Association of Short-Statured People and their Families (BKMF e.V.) since its establishment and development as a self-help organization from the late 1980s on. Since then, members and supporters have striven over around three decades for a fulfilled and self-determined life for people affected by short stature and for their equal participation in society. From the very beginning, communication and collaboration with professionals from medicine and other disciplines, with industry players and policy makers as well as with other self-help organizations were key activities of the Association. As one such step the BKMF setup a scientific advisory board to back its activities with professional expertise. Medical workshops and publications have resulted from this collaboration and have contributed to the growing reputation of the Association. Diagnostic and therapeutic guidelines were developed that are based on the experience of groups of experts, the short-statured people and the professionals. Moreover, two achievements made a major contribution to the ongoing competence provided by the BKMF e.V. The first of these was the establishment of the German Centre for People with Restricted Growth (DZK) – a conference and training centre that offers conference and show rooms, a sample apartment to test and promote supportive designs for adapted housing, a specialist library and space for a professionalized federal administration office. Second, the BMKF conducted research and participated in national and international research programmes with psychologists and physicians working at the Centre, who contributed with their expertise to the provision of information to short-statured people and their families. This dual and increasingly professional competence was of great importance for the development of the association as a self-help organization for the benefit of its members.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):73-77

doi: 10.17458/per.vol15.2017.kli.successfulwaybkmf

 

 

 

 

 

Self-Awareness of Growing Up with Short Stature

Structured Social Care for Children

Patricia Carl, Julika Innig, Marco Frerichs

Abstract

In this article two short statured young women talk about their particular challenges when growing up. To be short means, you are always the centre of attention with advantages and disadvantages. At the age of 30 years both resumed, it balances itself out. Attention may be positive but is sometimes exhausting and offending to always be the middle of attention.

In order to cope with today’s achievement-orientated society BKMF e.V. developed for children and adolescents with restricted growth a structured program how to cope with the challenges and barriers of today’s life. Exchange of experiences as well as transfer of knowledge gives them support for self-determination in life. Especially for short-statured adolescents, their brothers and sisters, the BKMF e.V. has been holding different seminars giving information on job training, gaining skills as well as recreational activities.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):78-81

doi: 10.17458/per.vol15.2017.cif.selfawarenessgrowingup

 

The Annual Convention at Hohenroda

Mischa Henze

 

Abstract

Each year the annual convention for people with restricted growth predominantly due to skeletal dysplasia, a 4-day event, is taking place in the middle of Germany with more than 600 participants and speakers. Beside an outstanding leisure program for kids and families, the meeting enclose workshops on various topics, including legal, social and medical aspects. Participants are children, adolescents and adults with restricted growth with different diagnoses and professionals. Apart from the organized workshops the focus has always been on the direct exchange between participants.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):82-84

doi: 10.17458/per.vol15.2017.hen.annualconventionhohenroda

 

Patients with Silver-Russell-Syndrome from Birth to Adulthood: Diagnosis, Development and Medical Care

Hartmut A Wollmann, MD, PhD, Michael B Ranke, MD, Prof emeritus

Abstract

Silver-Russell syndrome (SRS) is a rare congenital disorder, characterized by a wide spectrum of signs and symptoms, which vary significantly between affected individuals. The understanding of the genetic basis of the phenotype has advanced greatly during the past decades. Together with the typical clinical picture intrauterine growth retardation and severe short stature are the key features. Failure to thrive in conjunction with frequent feeding problems in infancy and early childhood are a major challenge for the parents. In parallel to the genetic research, medical care of these children improved dramatically, and this article describes the most important issues. Treatment of short stature with rhGH as part of the approved SGA indication is able to improve growth and final height in these children. This article reviews some of the major aspects related to some of these issues.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):85-91

doi: 10.17458/per.vol15.2017.wor.patientssilverrussell

 

The Importance of Networking in Pseudohypoparathyroidism: EuroPHP Network and Patient Support Associations

Agnès Linglart, MD, PhD, Giovanna Mantovani, MD, PhD, Intza Garin, PhD, Alessia Usardi, PhD, Francesca Marta Elli, MS, PhD, Guiomar Perez de Nanclares, PhD

Abstract

Pseudohypoparathyroidism is a rare endocrine disorder with an estimated prevalence of 1/100,000. It is characterized by hypocalcemia and hyperphosphatemia in the absence of vitamin D deficiency or impaired renal function. Research studies during the last 20 years have led to the identification of the molecular underlying cause of the disease, the characterization of the clinical and biochemical characteristics and the observation of an overlap between genetic and clinical manifestations.

The creation of networks both for specialists (including endocrinologists, pediatricians, dermatologists, geneticists, molecular biologists…) and patients support groups brings up the opportunity of research advance, synergism and common objectives for families and investigators, improving the quality of information about the disease and its outcome, that, at the end, will improve both the knowledge and life of the patients and their families.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):92-97

doi: 10.17458/per.vol15.2017.lmg.pseudohypoparathyroidism

 

The Importance of Collaboration in Advancing Understanding of Rare Disorders:

US/EU Joint Initiative on Silver-Russell Syndrome

Jennifer B. Salem, MA, Irène Netchine, MD, PhD, Madeleine D. Harbison, MD

Abstract

Patient-support organizations can facilitate a significant change in the way rare disorders are approached. Besides connecting families with each other and directing patients to experienced medical specialists, these groups, by collaborating with government initiatives like COST, can effect the direction and funding of rare disease research. By concentrating the rare disease patient population and funneling them to specific centers of excellence, these organizations help build specialists’ experience and their study populations. It requires a basic spirit of collaboration, driven parent leaders, a well-organized support platform, sources of funding, supportive clinical and research professionals and finally an effective method of collecting and disseminating information. Silver-Russell Syndrome is an excellent example of a rare disorder that has become better recognized, understood and treated because patient-support organizations, using the internet as a critical tool, have worked together with clinical care/research specialists and public funding agencies to build collaboration.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):98-101

doi: 10.17458/per.vol15.2017.snh.importancecollaborationadvancing

 

Guiding Registry for Skeletal Dysplasia. Rational Approach in Classification

Bernhard Zabel, MD, Jürgen Spranger, MD

Abstract

The official nosology and classification of genetic skeletal disorders lists more than 500 recognized diagnostic entities and groups them by clinical, radiographic and - if available - molecular data. The list helps in the diagnosis of individual cases, in the delineation of novel disorders, and in building bridges between clinicians and scientists. It can be the basis of a nosology-guided skeletal dysplasia registry and archive. An archive using a slightly modified classification system has been established in Magdeburg/Germany. Its benefits include: i. guidance of molecular testing, ii. disclosure of genetic heterogeneity, iii. delineation of new disorders, iv. disclosure of etiopathogenetic relationships, v. individual prognostication through follow-up. These items are illustrated with examples from classification subgroup 7, the spondylometaphyseal dysplasias. In contrast to usual, passive depositories we expect classifying registries to be living tools connecting researchers, students, patients and their relatives with each other and with self-help organisations.

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):102-108

 

 

doi: 10.17458/per.vol15.2017.zas.guidingregistryskeletaldysplasia

 

Understanding, Assessing and Improving Health-Related Quality of Life of Young People with Achondroplasia-

A Collaboration between a Patient Organization and Academic Medicine

Stefanie Witt, MA, PhD. student, Anja Rohenkohl, Dr. phil, Monika Bullinger, Prof. Dr. phil, Rachel Sommer, Dr. rer. biol. hum, Sabine Kahrs, Dipl. Psych, Karl-Heinz Klingebiel, Dipl. Soz. Arb, Ruzena Klingebiel, Julia Quitmann, Dr. phil

 

Abstract

Achondroplasia (ACH) is a rare, genetically determined health condition. Patients suffer from disproportional short stature and multiple physical and functional impairments as well as socioemotional problems. Despite the burden of disease, only few studies focus on health-related quality of life (HrQoL) of young ACH patients.

In a series of studies, the BKMF e.V. in cooperation with the UKE studied ACH patients’ and parents’ experience of HrQoL, their responses to HrQoL questionnaires and their evaluation of a HrQoL based intervention. Both qualitative and quantitative approaches were used.

Psychometrically appropriate instruments were identified and the wellbeing of young patients with ACH was analyzed showing no difference from a healthy norm sample using generic instruments. However, disease-specific instruments showed discrepancies between patients with proportional and disproportional short stature. Still, results show a significant effect by age and the evaluation of the counselling concept reveals that young ACH-patients especially benefit from such intervention.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):109-118

doi: 10.17458/per.vol15.2017.wrm.improvinghealthrelatedquality

 

Spontaneous Growth and Effect of Early Therapy with Calcitriol and Phosphate in X-linked Hypophosphatemic Rickets

Michele Cagnoli, MD, Roland Richter, MD, Peter Böhm, Kathrin Knye, MD, Susann Empting, Klaus Mohnike, MD, PhD

 

 

Abstract

Whereas nutritional vitamin D deficient rickets affects many people world-wide, X-linked hypophosphatemic rickets (XLH, MIM 307800) has a prevalence of only 1:25.000. Like other rare diseases burden of disease in XLH and the effect of the current standard of care are inadequately described.

Only few height data of untreated patients with XLH have been published. Here we report on height before start of therapy of 127 patients with XLH from 49 centres. One investigator collected all data from patient files documented at regular visits by treating physicians. Height standard deviation score (HSDS) was calculated and the geometrical mean was analysed. At birth all patients had a documented height within the healthy reference population. In this cross-sectional analysis of documented height at time of diagnosis decelerates until a mean age of 4.3 years to a nadir, i.e. lowest HSDS of -3.2 HSDS. Afterwards a spontaneous catch-up growth of +1.3 HSDS occurs until start of puberty.

To assess the impact of calcitriol and phosphate supplementation on growth we analysed from a cohort of 18 patients treated at the Dept. of Paediatrics at O.-v.-Guericke-University Magdeburg. In this subgroup, size at birth and all time lowest HSDS (r=0.56 p=0.002) are correlated as well as all time low HSDS and last height during puberty (r=0.62 p=0.001).

10 of 18 patients were treated before age 18 months. Within this group the mean HSDS decelerates to -2.2 SDS at age 4.4 y. and increased to -1.4 SDS at age 9.9 years. Adult height, i.e. mean age 17.6 years was -2.4 HSDS.

In conclusion, untreated children with XLR are characterized by normal length at birth, diminished growth rate compared to reference children until 4.3 years and spontaneous catch-up growth of 1.3 HSDS until start of puberty. Improved growth rate in XLR children occured by combined phosphate and calcitriol treatment before 18 months.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):119-122

doi: 10.17458/per.vol15.2017.crb.spontaneousgrowtheffect

 

Correlation of Bone Mineral Density on Quality of Life in Patients with Osteogenesis Imperfecta during Treatment with Denosumab

Heike Hoyer-Kuhn, MD, Christina Stark, MD, Jeremy Franklin, PhD, Eckhard Schoenau, MD, Oliver Semler, MD

Abstract

Osteogenesis imperfecta (OI) is a rare hereditary skeletal disease leading to recurrent fractures, short stature and impaired mobility. The phenotype varies from mildly affected patients to perinatal lethal forms. In most cases an impaired collagen production due to mutations in COL1A1 or COL1A2 cause this hereditary bone fragility syndrome with an autosomal dominant inheritance. Currently an interdisciplinary therapeutic approach with antiresorptive drugs, physiotherapy and surgical procedures is the state of the art therapy. The effect of such a therapy is evaluated by measuring different surrogate parameters like areal bone mineral density or by using different mobility tests or questionnaires. Up till now the impact of these parameters on quality of life of the patients is not evaluated. Currently pharmacological strategies are based on antiresorptive treatment with bisphosphonates. In this trial we investigated the effect of an antiresorptive therapy with the monoclonal antibody denosumab decreasing the activity of osteoclasts. Denosumab was administered subcutaneously in a dose of 1mg/kg body weight in 10 children with OI (5-10 years of age) every 12 weeks for 48 weeks. Areal bone mineral density, mobility, pain scores and quality of life were measured. The results showed a good effect of the treatment on bone mineral density but this improvement showed no correlation to pain and quality of life. In conclusion further trials have to define parameters to assess interventions which influence activities of daily life of the patients. An interdisciplinary approach including physicians, basic researchers and patient organisation is needed to focus research on topics improving quality of life of patients with severe skeletal diseases.

 

Ref: Ped. Endocrinol. Rev. 2017;15(Suppl1):123-129

doi: 10.17458/per.vol15.2017.hsf.correlationbonemineraldensity