Bruck syndrome - a rare syndrome of bone fragility and joint contracture and novel homozygous FKBP10 mutation.

Bruck syndrome is an autosomal recessive syndrome consisting of bone fragility and congenital joint contractures. According to the genotype, it has been classified into types 1 and 2. Recently, mutations in FKBP10, localised to chromosome 17q21, have been identified in some patients of Bruck syndrome. Twenty-seven patients of this syndrome have been reported so far. We present a new patient of this syndrome, with frequent fractures, congenital joint contractures, kyphoscoliosis, bilateral clubfoot, and pectus carinatum. The clinical and genetic features of all previously reported cases are also reviewed.

Effect of pubertal suppression on linear growth and body mass index; a two-year follow-up in girls with genetic short stature and rapidly progressive puberty.

OBJECTIVE: Gonadotropin-Releasing Hormone agonists (GnRHa) are used to improve the final adult height in short stature children. There are limited studies which address the potential side effect of these agents: excessive weight gain. We have followed girls with rapidly progressive puberty receiving GnRHa and results were focused on the effect of treatment on final height, weight and body mass index Methods: Thirty girls between 8.5 and 12 years with short stature and predicted adult height of less than 155 cm were enrolled in the study. All had rapidly progressive puberty. Weight and height measurements were done at the beginning of treatment, 6 and 12 months after starting and 6 and 12 months after the cessation of treatment. Bone age and stages of puberty were estimated at the beginning of treatment, after 12 months of starting and 12 months after the treatment was stopped. Findings : Predicted adult height (PAH) changes during treatment were not significant. There was no significant difference between final height and weight according to the body mass index (BMI), PAH or bone age. CONCLUSION: We conclude that girls with genetic short stature and rapidly progressive puberty will not benefit receiving a one-year course of GnRHa and there is no significant difference between the final height and final weigh among children according to BMI.

The side effects of gonadotropin releasing hormone analog (diphereline) in treatment of idiopathic central precocious puberty.

Treatment of central precocious puberty (CPP) is the administration of GnRH analogs. Metabolic syndrome comprised metabolic disturbances that confer increased risk of (CVD) diabetes mellitus (DM) and cardiovascular disease. This study is a longitudinal prospective study in pediatric endocrinology clinic. 30 non-obese children with idiopathic CPP were involved. Total body weight, height, blood pressure, BMI and waist circumference of the patients along with their triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting plasma sugar (FPS) were evaluated at the beginning and during 3 and 6 months GnRH analog therapy. All of the patients involved in this study were female with age 9.5±1.02 years. Waist circumference, weight and BMI were 69.3 cm, 37.21 kg, and 19.13 kg/cm(2) before therapy and 72.25 cm, 40.11 kg, and 19.54 kg/m(2) 6 months after therapy respectively. Mean systolic and diastolic blood pressure of the patients before therapy was 96.83 mmHg, 66mmHg and after 6 months therapy was 98.66 mmHg, 89.63 mmHg respectively. Mean TG, LDL, HDL and FPS were 90.06 mg/dl, 91.6 mg/dl, 43.7 mg/dl and 89.6 mg/dl before therapy and 96.4 mg/dl, 93.1 mg/dl, 44.7 mg/dl and 91.36 after 6 months therapy respectively. GnRH analog therapy doesn't cause metabolic syndrome after 3 and 6 month therapy but it may cause hyperlipidemia and central obesity.

Cardiovascular involvement in children with osteogenesis imperfecta.

OBJECTIVE: Osteogenesis imperfecta is a hereditary disease resulting from mutation in type I procollagen genes. One of the extra skeletal manifestations of this disease is cardiac involvement. The prevalence of cardiac involvement is still unknown in the children with osteogenesis imperfecta. The present study aimed to investigate the prevalence of cardiovascular abnormalities in these patients. METHODS: 24 children with osteogenesis imperfecta and 24 normal children who were matched with the patients regarding sex and age were studied. In both groups, standard echocardiography was performed, and heart valves were investigated. Dimensions of left ventricle, aorta annulus, sinotubular junction, ascending and descending aorta were measured and compared between the two groups. FINDINGS: The results revealed no significant difference between the two groups regarding age, sex, ejection fraction, shortening fraction, mean of aorta annulus, sinotubular junction, ascending and descending aorta, but after correction based on the body surface area, dimensions of aorta annulus, sinotubular junction, ascending and descending aorta in the patients were significantly higher than those in the control group (P<0.05). Two (8.3%) patients had aortic insufficiency and five (20%) patients had tricuspid regurgitation, three of whom had gradient >25 mmHg and one patient had pulmonary insufficiency with indirect evidence of pulmonary hypertension. According to Z scores of aorta annulus, sinotubular junction and ascending aorta, 5, 3, and 1 out of 24 patients had Z scores >2 respectively. CONCLUSION: The prevalence of valvular heart diseases and aortic root dilation was higher in children with osteogenesis imperfecta. In conclusion, cardiovascular investigation is recommended in these children.

Does congenital hypothyroidism have different etiologies in iran?

OBJECTIVE: To determine the prevalence of congenital hypothyroidism (CH), permanent and transient CH. METHODS: From November 2006 to September 2007, 63031 newborns were screened by measuring serum TSH obtained by heel prick. The neonates who had a TSH≥5mU/L were recalled for measurement of serum T(4), thyroid stimulating hormone (TSH) and TSH receptor blocking antibodies (TRBAb) in venous samples. In 43 primarily diagnosed as cases of CH, treatment was discontinued at age 2-3 years for 4 weeks and T(4) and TSH were measured again. Permanent or transient CH was determined from the results of these tests and radiologic evaluation. FINDINGS: The incidence of congenital hypothyroidism was found to be 1:1465 with a female to male ratio of 1.19:1. The most common clinical findings were prolonged jaundice (73%), large anterior fontanel (56%) and wide posterior fontanel (55%). In 43 patients with CH, prevalence of permanent and transient form of the disorder was 53.6% and 46.4% respectively. Permanent CH was associated with higher initial TSH level than transient hypothyroidism (P<0.001). The most common etiology of permanent CH was dyshormonogenesis (57%). TRBAb was found in 6.8% of the total 43 cases. CONCLUSION: Congenital hypothyroidism in Iran may have different etiologies. Due to higher rate of transient CH than other similar researches, it is reasonable to follow these patients for a longer period to rule out the possibility of permanent hypothyroidism.

The role of insulin like growth factor (IGF)-1 and IGF-binding protein-3 in diagnosis of Growth Hormone Deficiency in short stature children.

OBJECTIVE: The purpose of this study was to evaluate the role of IGF-1 and IGFBP-3 in diagnosis of short stature children and adolescents in whom Growth Hormone Deficiency (GHD) was found. METHODS: In this cross sectional study the referred short stature children and adolescents to Namazi Hospital in Shiraz- Iran, in 2003-2005 were studied. The inclusion criteria were proved short stature based on the physical examination, weight, height, standard deviation score (SDS) of height < -2, with considering stage of puberty and predicted height in children without any genetic or chronic disorders. The exclusion criteria were any positive physical or laboratory data suggesting hypothyroidism, rickets or liver disorders. For all patients a provocative growth hormone test was performed with propranolol and L-dopa and serum IGF-1 and IGFBP-3 were measured. GHD defined as peak(cutoff) serum GH level under 10 ìg/L and low IGF-1 and IGFBP-3 considered as cutoff serum level under -2 standard deviation. RESULTS: Eighty one short stature patients (39 boys and 42 girls) with mean age of 10.6 +/- 3.5 years completed the study. Seventeen patients with GHD were found and in 18 patients IGF-1 level were low. Only in 6 patients both GH and IGF-1 were low and 2 of them had low IGFBP-3. There were no correlations between the levels of GH,IGF-1 and IGFBP-3 in children with short stature due to GHD. The sensitivity and specifity of IGF-1 and IGFBP-3 in assessment of GHD were 35% and 81% for IGF-1 and 12% and 94% for IGFBP-3, respectively. CONCLUSION: No correlations were found between GH level and serum levels of IGF-1 and IGFBP-3 in short patients and the sensitivity of those tests in assessment of GHD were poor.

Reduced insulin growth factor I concentrations in iron-overloaded beta thalassaemic patients with normal growth hormone secretion and liver function.

We selected 92 subjects (46 females and 46 males), aged 10-15 years, from the Haematology and Endocrine Clinic of Shiraz University, Iran. Forty-six were beta thalassaemia patients (beta-Th) with short stature, 23 had idiopathic short stature (ISS) and 23 were healthy children with a standing height between the 10th and 95th percentile. Growth hormone (GH) secretion was normal in 23 beta-Th patients and reduced in the remaining 23 patients. A low insulin growth factor I (IGF-I) was found in 73.9% of beta-Th patients with GH deficiency, 56.5% of beta-Th patients with normal GH secretion to stimulation test and 8.7% of children with ISS. The reduced IGF-I concentration in beta-Th patients with normal GH secretion may be explained by partial insensitivity to GH (GHIS), neurosecretory dysfunction, low bioactive GH or increased proportion of circulating, non-22-kDa GH isoform. The possibility of GHIS in beta-Th patients with short stature indicates that higher doses of rechGH may be required to obtain an improvement in growth velocity in beta-Th patients.