Clinical, anthropometric, radiological and molecular characteristics of Egyptian achondroplasia patients

Background: Achondroplasia is the most common form of non lethal skeletal dysplasia. It is a fully penetrant autosomal dominant disorder and the majority of cases are sporadic resulting from de novo mutations associated with advanced paternal age. The phenotype of achondroplasia is related to disturbance in endochondral bone formation due to mutations in the fi broblast growth factor receptor-3 (FGFR3) gene. Aim of the Work: Evaluation of the cardinal phenotypic features in achondroplasia, the body physique using anthropometric measurements, the characteristic radiological signs in the patients as a main tool for diagnosis and detection of the most common mutations in achondroplasia patients in the studied sample.Subjects and Methods: From 42 cases referred to us as achondroplasia, we selected 20 cases where clinical manifestations were consistent with achondroplasia. Cases were subjected to full clinical examination, detailed anthropometric measurements, whole body skeletal survey and molecular studies of the most common mutations of the FGFR3 gene using PCR amplifi cation technique. Results: Nineteen cases were sporadic (95%) and one case had an affected father (5%). A paternal age above 35 years at the time of child’s birth was present in 7 cases (35%). Paternal exposure to occupational heat was noted in 6 cases (30%) and parental exposure to chemicals in 3 cases (15%). All cases showed typical clinical and radiological manifestations of achondroplasia. Anthropometricmeasurements quantitatively confi rmed the body physique in thestudied cases. G380R common mutations of the FGFR3 gene were detected in 15/18 cases (83%) with the G to A transition at nucleotide 1138 in 14 cases (77%). Agenesis of corpus callosum, not previously reported in association with achondroplasia, was present in the only case with the G-C transversio nmutation at nucleotide 1138 (5%).Conclusions: Awareness of the cardinal features of achondroplasia, properanthropometric measurements and detailed skeletal survey are the key foraccurate diagnosis, genetic counseling and avoidance of over diagnosis. The majority of studied Egyptian achondroplasia patients have the same common mutation that has been most often defi ned in patients with achondroplasia from other countries.Keywords: Achondroplasia, fi broblast growth factor receptor3,skeletal dysplasia, paternal heat exposure

Modification of myocardial substrate use as a therapy for heart failure

Despite advances in treatment, chronic heart failure is still associated with significant morbidity and a poor prognosis. The scope for further advances based on additional neurohumoral blockade is small. Effective adjunctive therapies acting via a different cellular mechanism would, therefore, be attractive. Energetic impairment seems to contribute to the pathogenesis of heart failure. The findings from several studies have shown that the so-called metabolic agents could have potential as adjunctive therapies in heart failure. These agents cause a shift in the substrate used by the heart away from free fatty acids, the oxidation of which normally provides around 70% of the energy needed, towards glucose. The oxygen cost of energy generation is lessened when glucose is used as the substrate. In this review we aim to draw attention to the metabolic alteration in heart failure and we present evidence supporting the use of metabolic therapy in heart failure