Congenital adrenal hyperplasia (CAH) due to CYP21A2 gene mutations is associated with a variety of clinical phenotypes (salt wasting, SW; simple virilizing, SV; nonclassical, NC) depending on residual 21-hydroxylase activity. Phenotypes and genotypes correlate well in 80–90% of cases. We set out to test the predictive value of CAH phenotype assignment based on genotype classification in a large multicenter cohort. A retrospective evaluation of genetic data from 538 CAH patients (195 screened) collected from 28 tertiary centers as part of a German quality control program was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C) and assigned clinical phenotypes correlated with predicted phenotypes, including analysis of Prader stages. Ultimately, concordance of genotypes with clinical phenotypes was compared in patients diagnosed before or after the introduction of nationwide CAH-newborn screening. Severe genotypes (null and A) correlated well with the expected phenotype (SW in 97 and 91%, respectively), whereas less severe genotypes (B and C) correlated poorly (SV in 45% and NC in 57%, respectively). This was underlined by a high degree of virilization in girls with C genotypes (Prader stage >1 in 28%). SW was diagnosed in 90% of screening-positive babies with classical CAH compared with 74% of prescreening patients. In our CAH series, assigned phenotypes were more severe than expected in milder genotypes and in screened vs prescreening patients. Diagnostic discrimination between phenotypes based on genotypes may prove overcome due to the overlap in their clinical presentations.
Stefan Riedl, Friedrich-Wilhelm Röhl, Walter Bonfig, Jürgen Brämswig, Annette Richter-Unruh, Susanne Fricke-Otto, Markus Bettendorf, Felix Riepe, Gernot Kriegshäuser, Eckhard Schönau, Gertrud Even, Berthold Hauffa, Helmuth-Günther Dörr, Reinhard W Holl, Klaus Mohnike and the AQUAPE CAH Study Group
Anita Hokken-Koelega, Aart-Jan van der Lely, Berthold Hauffa, Gabriele Häusler, Gudmundur Johannsson, Mohamad Maghnie, Jesús Argente, Jean DeSchepper, Helena Gleeson, John W Gregory, Charlotte Höybye, Fahrettin Keleştimur, Anton Luger, Hermann L Müller, Sebastian Neggers, Vera Popovic-Brkic, Eleonora Porcu, Lars Sävendahl, Stephen Shalet, Bessie Spiliotis and Maithé Tauber
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.
An expert panel meeting comprised of European paediatric and adult endocrinologists was convened to explore the current gaps in managing the healthcare of patients with endocrine diseases during transition from paediatric to adult care settings.
While a consensus was reached that a team approach is best, discussions revealed that a ‘one size fits all’ model for transition is largely unsuccessful in these patients. They need more tailored care during adolescence to prevent complications like failure to achieve target adult height, reduced bone mineral density, morbid obesity, metabolic perturbations (obesity and body composition), inappropriate/inadequate puberty, compromised fertility, diminished quality of life and failure to adapt to the demands of adult life. Sometimes it is difficult for young people to detach emotionally from their paediatric endocrinologist and/or the abrupt change from an environment of parental responsibility to one of autonomy. Discussions about impending transition and healthcare autonomy should begin in early adolescence and continue throughout young adulthood to ensure seamless continuum of care and optimal treatment outcomes.
Even amongst a group of healthcare professionals with a great interest in improving transition services for patients with endocrine diseases, there is still much work to be done to improve the quality of healthcare for transition patients.