Prevalence of Postoperation Metabolic Syndrome in Pediatric Liver Transplant Patients: A Single Center Experience.

OBJECTIVES: Metabolic syndrome components, such as being overweight or having hypertension, hyperlipidemia, or diabetes mellitus, are common complications after liver transplant in pediatric patients with probable multifactorial causes and increase the risk of cardiovascular complications in adulthood. In this study, our aim was to evaluate the prevalence of these components both before and after transplant surgery. MATERIALS AND METHODS: Our study included all children having liver transplant at our institution over a period of 20 years who were under 18 years old and had at least 6 months of posttransplant follow-up. Prevalence of metabolic syndrome components and pretransplant and posttransplant laboratory data of patients were evaluated. RESULTS: Over the 20-year study period, 391 liver transplant patients were included in our study, in which 167 were girls (42.7%) and 224 were boys (57.3%). Patients showed a posttransplant hyperlipidemia rate of 7.5%, hyperglycemia rate of 22%, hypertension rate of 9.6%, and metabolic syndrome rate of 50.2%. Pretransplant, the rate of patients with metabolic syndrome was 10.5%. CONCLUSIONS: Our study confirmed that the prevalence of metabolic syndrome in patients after liver transplant increases dramatically and should be explored with further research.

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.

Correlation of hypocalcemia with serum parathyroid hormone and calcitonin levels in pediatric intensive care unit.

OBJECTIVES: To investigate factors involved in causing hypocalcemia in critically ill patients. METHODS: The patients aged 1 mo to 18 y, admitted to PICU at Nemazee Hospital, from May through November 2012, were reviewed. Those with impaired calcium hemostasis or on vitamin-D supplement were excluded. Calcitonin and parathyroid hormone levels were checked if ionized calcium level was less than 3.2 mg/d. Patient's demographic data, length of stay, Pediatric Risk of Mortality-III (PRISM-III) score, the need for mechanical ventilation, inotropic drug administration and outcome were recorded. RESULTS: Among the 294 patients enrolled in the study, the incidence of ionized hypocalcemia was 20.4 %. The mortality rate was 45 % in hypocalcemic groups and 24.8 % in normocalcemic patients. Highly significant negative correlations were found between serum ionized calcium, PRISM-III score (r = -0.371, P = 0.004), and calcitonin level (r = -0.256, P = 0.049), but no significant correlation between hypocalcemia and parathyroid hormone level (P = 0.206) was found. A significant difference was observed between survivor and non-survivor groups regarding PRISM-III score (P = 0.00), ionized calcium (P = 0.00), and calcitonin (P = 0.022) but not parathyroid hormone level (P = 0.206). CONCLUSIONS: Hypocalcemia was associated with increased mortality rate in PICU patients. A negative correlation was found between ionized calcium level and calcitonin. There was also a link between PTH level and severity of illness. It can therefore be concluded that evaluating serum ionized calcium, calcitonin, and PTH levels can be used as prognostic factors in critically ill patients.

Measuring agreement between cervical vertebrae and hand-wrist maturation in determining skeletal age: reassessing the theory in patients with short stature.

INTRODUCTION: The objective of this study was to determine the degree of agreement between hand-wrist radiography and cervical vertebral maturation analysis in patients diagnosed with short stature. METHODS: A cross-sectional study was designed; 178 patients (90 girls, 88 boys) diagnosed with short stature and seeking treatment were selected. The patients were divided into 2 groups (76 with familial short stature, 102 with nonfamilial short stature). Hand-wrist and lateral cephalometric radiographs were obtained from the patients. The hand-wrist radiographs were analyzed using the Fishman method, and the lateral cephalometric views were categorized according to the method of Hassel and Farman. The degree of agreement between the 2 methods of predicting skeletal maturation was measured by calculating the contingency coefficient and the weighted kappa statistic. RESULTS: A high degree of agreement was observed between the 2 methods of analyzing skeletal maturation. It was also observed that agreement was higher in girls in the familial short-stature group, whereas boys had higher agreement in the nonfamilial short-stature group. CONCLUSIONS: Cervical vertebral maturation can be a valuable substitute for hand-wrist radiography in patients with short stature.

Adiponectin is a Good Marker for Metabolic State among Type 1 Diabetes Mellitus Patients.

OBJECTIVE: Adiponectin is secreted from adipose tissue. This hormone has a fundamental role in pathogenesis of insulin resistance, and has anti-inflammatory and anti-atherogenic effects. The objectives of this study were to compare serum adiponectin level between type 1 diabetics and healthy people and to assess its related factors, and also to determine the relationship between adiponectin and metabolic state. METHODS: This was a case control study involving 60 diabetics (25 good and 35 poor metabolic controlled) and 28 healthy persons (younger than 18 years old). The data about demographic (age and sex), clinical and paraclinical characteristics [body mass index (BMI), duration of disease, puberty state, and glycosylated hemoglobin (HbA1c) and adiponectin level in serum] were collected. Determinants of adiponectin were assessed using univariate and multiple linear regression analyses. FINDINGS: Mean (±SD) serum adiponectin level in healthy persons, good-controlled and poor-controlled type 1 diabetes mellitus patients were 9.16 (±4.2) µg/cc, 10.89 (±4.48)µg/cc, and 15.92 (±8.26)µg/cc, respectively. Post hoc analysis revealed that differences of adiponectin between poor- and good-controlled type 1 diabetes mellitus patients (P=0.01) and between healthy persons and poor controlled type 1 diabetes mellitus (P<0.0001) were statistically significant. Adiponectin level was associated with puberty state and BMI in healthy persons. It was associated with puberty state and HbA1c in type 1 diabetic persons. CONCLUSION: Serum level of adiponectin was higher in type 1 diabetics than in healthy persons and it can be used as a good marker for metabolic control state among diabetics.

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.

Thyroid hormone levels in children with liver cirrhosis awaiting a liver transplant.

OBJECTIVES: Evidence exists that decreased in triiodothyronine (T3) and thyroxine (T4) levels are associated with the severity of liver disease, and these hormones could be used as disease prognostic factors, but there are paradoxes in this regard in the literature. This study aimed at evaluating the correlation between thyroid hormone levels and severity of liver disease. MATERIALS AND METHODS: We measured thyroid hormone levels in 83 children with liver cirrhosis using radioimmunoassay techniques. RESULTS: Four patients (4.8%) showed a decrease in the amount of T3 and 9 patients (10.8%) revealed increased levels of T3. Also, decreases were seen in the T4 levels of 7 patients (8.4%), and 4 patients (4.8%) showed increases in levels of T4. The serum albumin levels were lower and international normalized ratio was higher in patients with low T3 and low T4. This study reveals that the Model for End-Stage Liver Disease and Pediatric End-Stage Liver Disease scores are statistically related to the decreased amounts of T4 (P = .036). The Model for End-Stage Liver Disease and Pediatric End-Stage Liver Disease scores and the Child scores were higher in low T3 patients, but this was not significant (P > .05). CONCLUSIONS: Decreased levels of thyroid hormones are correlated with the severity of disease and can be seen in more advanced cirrhosis. Patients with decreased T4 levels need a liver transplant more immediately than those patients that do not have decreased T4 levels.

Growth parameters in children with dyspepsia symptoms and Helicobacter pylori infection.

Controversy exists about relationship of H. pylori infection and somatic growth retardation of children. The aim of this study was to evaluate the relationship between H. pylori infection and growth parameters in children. 113 children with dyspepsia (4-18 years) were enrolled. C13 urea breath test was performed for determination of H.pylori infection. Height, weight, body mass index (BMI) and standard deviation score (SDS) was calculated and growth parameters were compared between two groups of H.pylori positive and those with negative results. The prevalence of H.pylori infection was 52.2%. There was no meaningful relation between calculated SDS (for height and BMI) and H.pylori infection.

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.

Evaluation of congenital hypothyroidism in fars province, iran.

OBJECTIVE: In Iran thyroid-stimulating hormone (TSH) based neonatal screening program is included in health care services from 2005 for detection of patients with primary congenital hypothyroidism (CH). This study was performed for a critical evaluation of the screening program primary congenital hypothyroidism in Fars province, Iran. METHODS: From November 2006 to September 2007, TSH serum concentrations of 63031 newborns, 3 to 5 days old born in Fars province, were measured by heel prick. The newborns with TSH ≥5mIU/L were recalled for measurement of serumT(4) and TSH in venous blood samples FINDINGS: Of 127 recalled subjects, 43 were confirmed to be hypothyroid, showing a prevalence of 1:1465 with F:M ratio of 1.05:1. The most common clinical and radiological findings were prolonged jaundice (73%), large anterior fontanel (56%), wide posterior fontanel (55%), absence of distal femoral epiphysis (20%), and umbilical hernia (11%). Scintigraphy of the thyroid with (99m)TC revealed eutopia (67.4%), hypoplasia (23.3%), agenesis (4.7%) and ectopia (2.3%). CONCLUSION: It is concluded that a cut off value of TSH≥5mIU/L overestimates recalling the number of patients with CH. The most common cause of congenital hypothyroidism is not dysgenesis of the gland and perhaps dyshormonogenesis in Iran is more common than what is reported in other countries.

Serum insulinlike growth factor-1 and its binding protein-3 levels in children with cirrhosis waiting for a liver transplant.

OBJECTIVES: Investigate the prognostic value of serum insulinlike growth factor-1 (IGF-1) and its binding protein 3 (IGFBP-3) in pediatric patients with liver cirrhosis, and investigate the correlation between these parameters and other available prognostic factors including Child-Pugh scoring, Pediatric End-Stage Liver Disease, and Mayo End-Stage Liver Disease scoring. MATERIALS AND METHODS: This prospective, case-controlled study was done at the Nemazee hospital for 12 months from August 2009 to August 2010. It included 45 pediatric patients (< 18 years) diagnosed with liver cirrhosis and 38 healthy age and sex-matched controls. The extent and severity of the liver disease was evaluated by the Child-Pugh classification and Pediatric End-Stage Liver Disease/Mayo End-Stage Liver Disease scores. Serum levels of IGF-1 and IGFBP-3 were determined and were compared to controls and their correlation with Child-Pugh and Pediatric End-Stage Liver Disease/Mayo End-Stage Liver Disease scores were investigated. RESULTS: The most-common cause of liver cirrhosis was biliary atresia being found in 11 patients (24.4%) followed by tyrosinemia in 8 (17.8%). IGF-1 serum levels were significantly lower in cirrhotic patients compared with controls (3.85 ± 3.69 nmol/L vs 41.79 ± 16.03 nmol/L; P < .001). Serum levels of IGFBP-3 also were significantly lower in patients with liver cirrhosis compared with healthy controls (46.66 ± 30.57 nmol/L vs 205.63 ± 25.52 nmol/L; P < .001). Serum levels of IGF-1 were significantly lower in patients with stage B (P = .047) and C (P = .036) of Child-Pugh classification compared with stage A. Serum levels of IGF-1 (r ≈ 0.227; P = .034) and IGFBP-3 (r ≈ 0.389; P = .008) were negatively correlated with Pediatric End-stage Liver Disease / Mayo End-stage Liver Disease scores. CONCLUSIONS: The serum levels of IGF-1 and IGFBP-3 are decreased in children with liver cirrhosis. The stage of liver dysfunction is correlated to serum levels of IGF-1 and IGFBP-3 in children. Thus, these 2 factors can be used for assessing the prognosis and outcome in those children with liver cirrhosis.

Ambulatory blood pressure monitoring in children and adolescents with type-1 diabetes mellitus and its relation to diabetic control and microalbuminuria.

Diabetes mellitus (DM) is now considered as the major cause of end-stage kidney failure, and hypertension (HTN) is one of the main determinants of progression of renal disease. The aim of this study was to assess the role of blood pressure (BP) by ambulatory blood pressure monitoring (ABPM) in children and adolescents with type-1 DM and its correlation with micro-albuminuria (MA) and diabetic control. Eighty-one patients with type-1 DM (mean age 13 ± 4 years), whose duration of DM was at least two years, were enrolled in this study. The prevalence of HTN based on ABPM was 28.4%, while by casual method it was 32.1%. The pattern of HTN was as follows: mean systolic HTN 27.2%, mean diastolic HTN 11.2%, daytime systolic HTN 17.3%, daytime diastolic HTN 6.2%, night systolic HTN 30.9%, and night diastolic HTN 29.7%. The systolic and diastolic BP loads were 33.4 and 27.2%, respectively. About 70.4% of the patients were non-dippers, 12.4% had masked HTN, and 3.7% had white coat HTN. The pre-valence of MA was 34.6% and that of abnormal HbA 1 c was 82.7%. There was no correlation between HTN and both MA and HbA 1 c; also, no correlation was found between the duration of diabetes and HbA 1 c. Moreover, no significant correlation was found between the duration of diabetes and MA (P = 0.080). Despite the high prevalence of abnormal BP profile among diabetic children, prospective longitudinal studies considering the other major risk factors, particularly genetic factors, which have an impact on the progression to diabetic nephropathy, are recommended.

Serum resistin level in obese male children.

Objectives. Resistin is a member of cysteine-rich molecules. Several studies have been carried out to determine the biological effect of resistin, nevertheless a significant number are animal studies. All the studies performed regarding the relationship between serum resistin and obesity were merely accomplished in women. To the best of our knowledge, there is no survey on the correlation of the serum resistin level and obesity in male children. The aim of the present study is to assess serum concentration of resistin in obese male children. Methods. Between June 2009 and January 2010, we enrolled 42 randomly selected obese male students (body mass index (BMI) >95th percentile, age 15.7 ± 1.5). Thirty-eight healthy age-matched male students with normal BMI (<85th percentile) were selected as a control group for the purpose of comparison of the serum resistin levels. Results. Serum resistin levels were measured in obese and control group. No significant difference was found between resistin levels of the 2 groups (obese: 9.21 ± 5.6 ng/mL versus normal: 9.83 ± 4.3 ng/mL; P = .582). There was no significant correlation between serum resistin level and BMI. Assessing the resistin level in male subjects was the distinct feature of our study. The outstanding finding of this research is that there is no correlation between serum resistin level and obesity. Conclusion. We have demonstrated that there is no correlation between obesity in male children and resistin level. Consequently, metabolic abnormalities of insulin resistance seen in obese male patients are not related to resistin.

Autoimmune polyglandular syndrome type 2: an unusual presentation.

Autoimmune polyglandular syndrome (APS) type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus. APS type 2 occurs most often in middle aged females and is rare in children. Here an 11 year old boy is reported with Addison's disease who developed symptom's of diabetes mellitus, goiter, malabsorption, macrocytic anemia and keratitis. APS type 2 occurs most often in middle aged females and is quite rare in children but one should think to autoimmune poly glandular syndrome type II in patient at any age especially in patients with Addison's disease.

Incidence of neonatal hyperphenylalaninemia in fars province, South iran.

OBJECTIVE: Phenylalanine hydroxylase or its cofactor, tetrahydrobiopterin (BH(4)), deficiency causes accumulation of phenylalanine in body fluids and central nervous system. Considering the fact that hyperphenylalaninemia is a preventable cause of mental retardation in infants, the objective of this study was to determine the incidence of congenital hyperphenylalaninemia in Fars province, south of Iran. METHODS: In a period of one year from November 2007 to November 2008 blood samples were withdrawn from all newborns born in Fars province for measurement of serum phenylalanine. The samples with a serum level of≥ 2 mg/dl were referred to pediatric endocrine clinic for confirmation and determination of the type of hyperphenylalaninemia by quantitive serum phenylalanine measurements by using High-Pressure liquid chromatography (HPLC) method. FINDINGS: Nine out of 76966 newborns had a serum phenylalanine level≥2mg/dl, of which 8 cases were confirmed by HPLC. The incidence of the disease was 1:10000. The incidence of mild hyperphenylalaninemia and phenylketonuria (PKU) among the patients was 62.5% and 37.5% respectively and the incidence of BH(4) deficiency was 1/76966. CONCLUSION: These findings indicate a high incidence of hyperphenylalaninemia, in the newborns from Fars province. The high incidence makes a comprehensive screening program for management of the disease necessary.

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.

Insulin-like growth factor-1 levels in children with Beta-thalassemia minor.

OBJECTIVE: Growth retardation in children with b-thalassemia major is multifactorial. Some etiologies described for this condition are hemochromatosis, disturbed growth hormone (GH) / insulin growth factor-1 (IGF-1) axis, undernutrition and hypermetabolism. It has also been proven that growth retardation is present in b-thalassemia major children despite regular transfusion and chelation. Our aim was to evaluate the level of IGF-1 in b-thalassemia minor subjects and compare it with that in healthy children. METHODS: Fifty children aged 6 months to 15 years with b-thalassemia minor (32 males, 18 females) and 50 age- and sex-matched normal healthy children were selected. Medical history was taken and complete physical examination was done in each case; IGF-1 level was checked in all cases. This study was done in Shiraz, southern Iran, during 2005. RESULTS: IGF-1 levels were significantly lower in b-thalassemia minor children than normal children (P = 0.015). This result demonstrates that some etiologies of growth failure in b-thalassemia major other than those described to date can exist, which may be shared with b-thalassemia minor in feature or may be transformed by genes that are either expressed or not. CONCLUSION: We conclude that in addition to that observed in b-thalassemia major, IGF-1 level is also decreased in b-thalassemia minor, and these two may have similar etiologies.

Failure of puberty and linear growth in beta-thalassemia major.

Thalassemia major is a severe progressive hemolytic anemia and a serious medical problem worldwide. Endocrine dysfunctions are well described in patients with thalassemia major. Data for endocrine complications from developing countries are scant. Endocrine complications in developing countries may be frequent due to suboptimal iron chelation. The aim of this study was to evaluate the prevalence of delayed puberty and growth failure in patients with beta-thalassemia major. We evaluated the growth and sexual development of 146 patients with thalassemia major aged 10-22 years. The following data were recorded in questionnaire, age, sex, height, weight, serum ferritin levels and pubertal staging. Failure of puberty was present in 75.6% of boys and 68.4% of girls aged 12-22 years. Gonadotropin insufficiency was found in most of the patients with lack of puberty. There was a significant difference between the height of patients with pubertal development (153 ± 9.1 cm) and those with delayed puberty (140 ± 9.1), (p< 0.001). Short stature was present in 65.7% of patients. Sixty-nine percent of boys and 62.9% of girls were found to be less than 2 SD below the mean for normal height; after the age of 12, the percentage was 78.9% in girls and 83.8% in boys after the age of 14. We conclude that failure of puberty and impaired growth are very common in our thalassemic patients which necessitates newer protocols of treatment, correct blood transfusion and chelation therapy.

Body mass index in children with beta-thalassemia major.

Underweight or low body mass index (BMI) is associated with developing many health problems. Despite the presence of many growth abnormalities in patients with beta thalassemia major, BMI has not been adequately studied. All of the thalassemic patients under 18 years of age, registered in thalassemia center of Shiraz, were studied. Medical history was taken and complete physical examination was done. BMI (weight/height2) at different ages was calculated and compared with standardized percentile curves of BMI for children and adolescents. BMI less than 10th percentile for sex and age was observed in 12.4% of thalassemic patients under 10 years of age and in 46.5% of patients above 10 years of age (p< 0.000001). Also the observed difference between girls and boys, specially when they are more than 10 years of age is significant (p< 0.000001). Underweight is a common finding in patients with beta-thalassemia major specially when they are older than 10 years of age. This is possibly because of the occurrence of multiple endocrinopathies and also the presence of under-nutrition in these patients. So growth should be monitored routinely at regular intervals in order to detect any decline in growth velocity and also any derangement in BMI to establish an appropriate protocol for investigation and treatment.