Mean Height Standard Deviation Score Research Articles

Early or Late Transplantation in Congenital Nephrotic Syndrome: Which is Effective for Optimal Growth?

Congenital nephrotic syndrome (CNS) is a genetic disease that is present in the antenatal period or during the first 3 months of life. In this study, we aimed to compare growth parameters of patients with CNS who received kidney transplants and either (1) had a normal glomerular filtration rate (GFR) at the time of transplant or (2) chronic kidney disease (CKD) at the time of transplant. Patients with a diagnosis of CNS who had a minimum follow-up period of 6 months were evaluated retrospectively. Children at stages 4 or 5 CKD or patients receiving dialysis during the pretransplant period were defined as group 1; patients with normal GFR at the time of transplantation were classified as group 2. Short stature and low weight were defined as less than −2 standard deviation scores (SDS) for height and weight according to their age. A total of 17 patients were included in the study. Thirteen of 17 patients had NPHS1 gene mutations. Group 1 and group 2 consisted of 8 and 9 patients, respectively. Mean height SDS and mean weight SDS in group 2 were higher than group 1 in the pretransplant period (−4.34 ± 1.74 vs −2.84 ± 1.56; P = .011 and −3.54 ± 0.93 vs −1.83 ± 1.13; P = .008). In the post-transplant period, the significant difference in height SDS continued in favor of group 2 (−3.16 ± 1.11 vs −1.16 ± 0.87; P = .002). The short stature rate was 83% in group 1 and 72% in group 2 in the pretransplant period (P = .62), and 83% in group 1 and 27% in group 2 in the post-transplant period (P = .02). Early renal transplantation seems to be effective for optimal height gain in children with CNS.

Determinants of Statural Growth in European Children With Chronic Kidney Disease: Findings From the Cardiovascular Comorbidity in Children With Chronic Kidney Disease (4C) Study.

Failure of statural growth is one of the major long-term sequelae of chronic kidney disease (CKD) in children. In recent years effective therapeutic strategies have become available that lead to evidence based practice recommendations. To assess the current growth performance of European children and adolescents with CKD, we analyzed a cohort of 594 patients from 12 European countries who were followed prospectively for up to 6 years in the 4C Study. While all patients were on conservative treatment with a mean estimated glomerular filtration rate of 28 ml/min/1.73 m2 at study entry, 130 children commenced dialysis during the observation period. At time of enrolment the mean height standard deviation score (SDS) was −1.57; 36% of patients had a height below the third percentile. The prevalence of growth failure varied between countries from 7 to 44% Whereas patients on conservative treatment showed stable growth, height SDS gradually declined on those on dialysis. Parental height, pubertal status and treatment with recombinant growth hormone (GH) were positively, and the diagnosis of syndromic disease and CKD stage were negatively associated with height SDS during the observation period. Unexpectedly, higher body mass index (BMI) SDS was associated with lower height SDS both at enrolment and during follow up. Renal anemia, metabolic acidosis, and hyperparathyroidism were mostly mild and not predictive of growth rates by multivariable analysis. GH therapy was applied in only 15% of growth retarded patients with large variation between countries. When adjusting for all significant covariates listed above, the country of residence remained a highly significant predictor of overall growth performance. In conclusion, growth failure remains common in European children with CKD, despite improved general management of CKD complications. The widespread underutilization of GH, an approved efficacious therapy for CKD-associated growth failure, deserves further exploration.

OR17-4 Transcon Growth Hormone In The Treatment Of Pediatric Growth Hormone Deficiency: Results Of The Phase 3 Height Trial

TransCon Growth Hormone in the Treatment of Pediatric Growth Hormone Deficiency: Results of the Phase 3 heiGHt Trial Background TransCon Growth Hormone is a sustained-release recombinant human growth hormone (hGH; somatropin) prodrug in development as a long-acting GH (LAGH) for children with growth hormone deficiency (GHD). In its prodrug form, TransCon hGH is inactive with hGH transiently bound to a TransCon carrier via a TransCon linker. Upon injection and triggered by physiological pH and temperature, unmodified recombinant hGH is sustainably released and thus designed to maintain the same mode-of-action and distribution as daily hGH replacement therapy but with once-weekly dosing. In a 6-month phase 2 trial of TransCon hGH vs. a daily hGH in children with GHD, mean annualized height velocity (AHV) for TransCon hGH was 12.9 cm/y compared to 11.6 cm/y for a daily hGH at an equivalent hGH dose (0.21 mg/kg/wk). The subsequent pivotal phase 3 global heiGHt Trial (ClinicalTrials.gov: NCT02781727) was designed to investigate the safety, tolerability, and efficacy of weekly TransCon hGH versus daily hGH over 52 weeks in treatment-naive prepubertal children with GHD. Methods Subjects were randomized in a 2:1 ratio and received either once-weekly TransCon hGH 0.24 mg hGH/kg/wk or dose-equivalent once-daily Genotropin over 52 weeks. Key baseline demographics variables included age, gender, height standard deviation score (SDS), IGF-1 SDS, peak stimulated GH, and bone age delay. Study endpoints included AHV, IGF-1 response, immunogenicity, and safety. Results At baseline, the mean age of study participants, of whom 82% were male, was 8.5 years. Mean height SDS was -2.93, and mean IGF-1 SDS was -2.04. Mean peak stimulated GH was 5.77 µg/L, and mean bone delay was 2.63 years. The final sample size (n=161) was larger than planned (n=150) which strengthens the study power for noninferiority. Top-line results, including AHV, change in height SDS, serum IGF-1 levels, change in bone age, and adverse events, will be available for presentation at ENDO 2019. Conclusion Only LAGHs based on unmodified hGH have obtained approval in Europe or the United States. By February 2019, all subjects will have completed their participation in this pivotal trial of a LAGH designed to release unmodified hGH, with top-line analyses available in March. The heiGHt Trial was well-powered to demonstrate noninferiority between TransCon hGH and a daily hGH, with baseline demographic variables in the range of recent GH trials.

SUN-260 The Severity of GH Deficiency (GHD) Does Not Affect Adherence to Treatment in GHD Prepubertal Children Taking rh-GH via the Easypod Device

Introduction: The success of GH therapy, as in other chronic conditions, depends on the patient’s ability to maximally adhere to their treatment regimen. Low adherence to GH therapy has been reported in several studies, and shown to be correlated with age, socioeconomic status, treatment duration, the use of an injection device among others, although data are controversial. Recent studies have shown that GH deficient (GHD) patients naïve to treatment have better adherence rates than non-naïve ones, while no data exist on the effect of the severity of GHD on adherence to treatment. The Easypod Connect Observational Study (ECOS) is a prospective long-term observational study involving 24 countries aimed at evaluating the level of adherence in patients receiving growth hormone via the Easypod device. The Easypod device allows an automatic objective measure of adherence over time. The ECOS database provides adherence rates of a large number of patients receiving growth hormone via the Easypod device. Objective: to compare adherence to GH treatment in patients with high likelihood of being severe GHD (SGHD) with a group of non-severe GHD (NSGHD). Patients and methods: The group of SGHD included 17 naïve GHD prepubertal (aged 2 to 10 y in girls and 2 to 12 y in boys) patients (13 boys and 4 girls) with organic or genetic or congenital GHD. All had height-SDS <-2.5 at start of treatment and/or first year change in height >0.5 standard deviation score (SDS). The group of NSGHD included 49 naïve to treatment prepubertal (35 boys and 14 girls) with idiopathic GHD, and height SDS ≥-2.5 at start of treatment. After 2 and 3 y of treatment, respectively 15 and 12 patients were available in the SGHD group, and 37 and 22 in the NSGHD group. Differences in adherence rates between the groups were tested with the unpaired two-samples Wilcoxon test. Results: Mean (SD) height SDS at start was -2.7 (1.4) in SGHD and -2.1 (0.3) in NSGHD, and mean (SD) first year change in height SDS was 0.9 (0.5) in SGHD and 0.6 (0.3) in NSGHD. Adherence rates in the first three years of treatment were not significantly different (p>.1) between the two groups with medians of 92%, 88%, and 95% respectively in SGHD, and 93%, 90%, and 92% respectively in NSGHD. Conclusions: Our data confirm that naïve GHD children receiving GH treatment with the Easypod device have a good adherence to treatment up to three years. Our findings also show that the severity of GHD does not seem to affect adherence to treatment in prepubertal children.

SUN-258 Prediction of Height Two Years after Start Treatment in Children with Growth Hormone Deficiency

Background: Various prediction models for the growth response to recombinant human growth hormone (rhGH) have been published, but none of these have been able to incorporate data on adherence to rhGH treatment. Previous studies have shown that suboptimal adherence negatively affects the growth response in the first two years of rhGH treatment. The availability of the easypod electronic drug-delivery device which continuously assesses adherence, enables to develop a prediction model taking adherence into account. Aim: To develop a model for prediction of height standard deviation score (HSDS) two years after start treatment, using information available at the start of GH treatment and adherence in the first two years. Patients and Methods: We included prepubertal children with idiopathic isolated growth hormone deficiency (GHD) participating in the easypod connect observational study (ECOS), a 5-year, Phase IV open-label study to continuously assess real-world adherence via the easypod device. Inclusion criteria were GHD, naïve to rhGH treatment, age <10y in girls and <12y in boys, height and adherence available in the first and second year, target height, birth weight, gestational age, and information on GH dose. Linear regression analyses were performed to construct a prediction model for HSDS 2y after start treatment, with age at start, HSDS at start, target height (TH) SDS, birth weight SDS, GH dose, gestational age (<37 weeks vs ≥37 weeks), sex, and adherence in the first and second year as potential predictors. Stepwise backward regression analyses were performed to simplify the model without a statistically significant loss of fit with a model fit criterion of p<0.1 for each predictor. Results: In total, 132 patients complied with the inclusion criteria. Mean (SD) HSDS was -2.4 (0.9) and age at start 6.5 (2.0) yrs. The prediction model was: HSDS at 2y after start treatment = 0.4699 - 0.0627 x Age at start + 0.7904 x HSDS at start + 0.1216 x TH SDS + 0.0418 x birth weight SDS + 0.1659 x sex (male) + 0.0050 x adherence in the second year. P-values were <.001 for HSDS at start and adherence in the second year, .002 for Age at start, and .07 for TH SDS, birth weight SDS and sex. This model explained 76% of the total variance. For example, if a girl starts with GH treatment at 6.5y with a HSDS of -2.4, TH SDS of 0, birth weight SDS of 0 and 100% adherence in the second year, her predicted HSDS 2y after start treatment is -1.3 SD. If she misses 2 injections/week in the second year, the predicted HSDS 2y after start treatment is -1.5 SD. Conclusion: We have developed a prediction model for height two years after start treatment for children with GHD. This model can be used to study the impact of information available at the start of GH treatment and adherence in the second year. More research is needed to explore the effect of individual patterns of adherence on growth in real word settings.

Mutation spectrum and pivotal features for differential diagnosis of Mucopolysaccharidosis IVA patients with severe and attenuated phenotype

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic mutations in GALNS gene and characterized by progressive skeletal deformities with short stature. The aim of this study was to evaluate the genotype, longitudinal height measurement and clinical features of MPS IVA patients. Thirty-two patients from 22 families were enrolled. The ages of patients at diagnosis ranged from two months to 18 years of age, and followed up for three to twenty years. They were classified as severe and attenuated form (intermediate and mild) according to their height measurements. The mean height standard deviation scores (SDS) for Turkish standards at 0–3, 5 and 10 years of ages were found to be −1.1, −4.2 and −7.3 respectively in patients with severe phenotype, while they were +0.4, −1.5 and −3 for intermediate phenotype. Patients with severe form reached a mean final height of −8.5 SDS, and mild phenotype −3.6 SDS. The most common initial and current symptoms in the patients with the severe phenotype were pectus carinatus and/or kyphosis deformities which occurred between 5 months and 3 years of age, and genu valgum deformity which developed after 3 years of age. However, kyphoscoliosis was the most common initial and current findings in the attenuated phenotype. Although, initial symptoms appeared in early childhood in the intermediate phenotype, similar to the severe phenotype, the clinical findings progressed slowly and genu valgum deformity did not develop. In patients with mild phenotype, the onset of symptoms was after 5 years of age. In conclusion, this study provides significant insights into the initial and follow-up clinical features and height values that contribute to the differential diagnosis of the severe and intermediate phenotypes in early childhood. Eleven mutations in GALNS gene in which one of them is novel (c.416G>A) were associated with the severe phenotype and three mutations (c.1038C>A, c.850T>G, c.752G>A) lead to the attenuated phenotype.

Evaluation of growth in children and adolescents after renal transplantation.

Büyükkaragöz B, Bakkaloğlu SA, Tuncel AF, Kadıoğlu-Yılmaz B, Karcaaltıncaba D, Paşaoğlu H. Evaluation of growth in children and adolescents after renal transplantation. Turk J Pediatr 2019; 61: 217-227. Despite the advances in the last decades, it is well-known that optimal growth is usually not achieved in children with chronic kidney disease (CKD) even after successful renal transplantation (RTx). In this study, our aim was to evaluate growth patterns and factors affecting growth in pediatric and adolescent renal transplant recipients (RTR). Thirty-seven prevalent RTR with mean age of 17.0±2.9 years and mean post-RTx duration of 4.2±2.0 years were evaluated. Growth parameters, height velocities and factors affecting growth at the time of RTx (baseline) and in the post-RTx follow-up were also retrospectively assessed. Cumulative corticosteroid (CS) doses were calculated. Mean height and weight standard deviation score (SDS) values were negative (-1.4±1.1 and -1.2±1.5, respectively), whereas height SDS was positive in 16% of the patients. Mean weight, height, and BMI (body mass index) SDS of the RTR were significantly higher than the values at transplantation (p < 0.001 for weight and height SDS; p < 0.05 for BMI SDS). Height SDS was < -2.0 in 19% of the patients while 60% at the baseline. Main factors associated with post-RTx height SDS were pre-RTx height SDS (B: 0.448, p < 0.01) and CKD duration (B: -0.01, p < 0.05). Although it was much better than the pre-RTx period, the present study reveals that post- RTx growth was less than anticipated. As well as minimizing post-RTx CS doses and preserving graft function in the post-RTx follow-up, performing early transplantation and all efforts for minimizing pre-RTx growth deficit are crucial for an optimal post-RTx growth.

Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV prospective observational study.

Country-specific data on outcomes of treatment with recombinant human growth hormone are lacking. We present such data for children treated with growth hormone in Canada. We describe characteristics and outcomes of 850 children (mean age at baseline 8.5 yr) treated with growth hormone constituting the Canadian cohort of the multinational phase IV prospective observational Genetics and Neuroendocrinology of Short-stature International Study (GeNeSIS). The diagnosis associated with short stature was as determined by the investigator. Auxological data were evaluated yearly until near-adult height. Adverse events were assessed in all growth-hormone-treated patients. The diagnosis ascribed as the cause of short stature was growth hormone deficiency in 526 children (61.9%), predominantly organic rather than idiopathic, particularly congenital pituitary abnormalities and intracranial tumours. All diagnostic groups with sufficient patients for analysis had increased height velocity standard deviation score (SDS) and height SDS during growth hormone treatment. For patients who reached near-adult height (n = 293), the mean height SDS was within the normal range for about 80% of patients with organic growth hormone deficiency (n = 131) or idiopathic growth hormone deficiency (n = 50), 50% of patients with idiopathic short stature (n = 10) and 46% of patients with Turner syndrome (n = 79). Eleven deaths were reported, 7 in patients with organic growth hormone deficiency. Serious adverse events considered related to growth hormone treatment (n = 19) were isolated except for medulloblastoma recurrence (n = 2) and adenoidal hypertrophy (n = 2). Growth hormone treatment was effective and had a good safety profile in Canadian children. Growth hormone dosages were lower than in the US and global GeNeSIS cohorts, and a greater proportion of treated Canadian children had organic growth hormone deficiency. ClinicalTrials.gov, no. NCT01088412.

Growth Failure in a Series of Iranian Patients with Juvenile Idiopathic Arthritis

Background: Juvenile Idiopathic Arthritis (JIA) is accompanied by growth failure, mostly occurring due to chronic inflammation and use of corticosteroids for treatment. The aim of our study was to determine the prevalence of short stature in JIA patients and possible systemic disorders which may affect the growth pattern in this group of patients. Methods: In this cross-sectional study erformed from June 2014 to May 2015, JIA patients with a history of more than one-year treatment were examined by an endocrinologist and based on their height standard deviation score (SDS) two groups were determined: Group A > -2SD and group B < -2SD. Complete blood count, thyroid function tests and 25OHD3 level were assessed in both groups, but other laboratory tests, including liver and renal function tests, growth hormone stimulation test, urine analysis and culture, as well as left hand and wrist X-ray for bone age determination, were done in group B. Results: Of 117 JIA patients who were enrolled, 41 patients were under -2SD (19% of pauciarticular, 62% of poly articular and 33% of systemic onset). The mean height SDS in group B was -3.48 ± 1.28 (compared to -0.9 ± 0.8 in their parents). We found hypovitaminosis D in 73% of our patients. The prevalence of subclinical hypothyroidism was 7.4% (5% of group A and 9.7% of group B). Twenty-four percent (10 patients) of group B did not respond to growth hormone (GH) stimulation test and 14.6% of them (6 patients) were possibly GH resistant. Liver function tests and renal function tests were normal in all the patients. There was no difference between 2 groups in hypothyroidism and hypovitaminosis D but polyarticular type of the disease was associated with short stature (P Value < 0.000). Conclusions: Growth failure is common in JIA patients. So they, especially those with polyarticular type, need to be visited periodically by an endocrinologist.

Clinical follow-up data and the rate of development of precocious and rapidly progressive puberty in patients with premature thelarche.

We aimed to evaluate the clinical follow-up data of patients with premature thelarche and determine the rate of development of precocious and early puberty in these patients. The charts of 158 girls with premature thelarche who were followed-up in our pediatric endocrinology polyclinic were reviewed. The patients were divided into three groups according to the age at onset: group 1 (0-1 month) (n=12), group 2 (1-24 months) (n=40) and group 3 (2-8 years) (n=106). At admission, the mean height standard deviation score (SDS), body weight (BW)-SDS, body mass index (BMI) and BMI-SDS were significantly higher in group 3 than in group 1 and group 2. At admission, 8.8% of the patients were obese and 24% of the patients were overweight. The majority of patients who were obese and overweight were in group 3. At the end of the follow-up, thelarche regressed in 24.7%, persisted in 32.9%, progressed in 25.9% and had a cyclic pattern in 16.5% of the patients. Precocious or rapidly progressive puberty developed in 47 of the 158 patients (29.7%). The mean age at progression to early or rapidly progressive puberty was 98.1±17.6 months. A total of 89.3% of the patients who progressed to early or rapidly progressive puberty were in group 3. Precocious or rapidly progressive puberty developed in 29.7% of subjects with premature thelarche. As patients who developed rapidly progressive puberty had a higher BW-SDS and BMI-SDS than those who did not, it is suggested that the increase in weight could stimulate rapidly progressive puberty in cases with premature thelarche.

PROFILE OF BOYS WITH POSTERIOR URETHRAL VALVES FROM A TERTIARY CARE CENTER IN A DEVELOPING COUNTRY

Introduction: Posterior urethral valves (PUVs) are the most common cause of obstructive uropathy in boys. While most patients&nbsp;in developed countries are diagnosed in the antenatal period, our patients often present late which adversely affects their outcome.&nbsp;This retrospective study was aimed to study the clinical profile of boys with PUV at follow-up. Methods: Records of 45 boys&nbsp;&nbsp;with PUV who were in follow-up for at least 1-year were retrieved between February and December 2015. Age of presentation,&nbsp;signs and symptoms, anthropometry, radiological findings, surgical interventions, and biochemical investigations were recordedin a pre-structured pro forma. The data were later analyzed on an Excel spreadsheet. Results: The mean age at the diagnosis&nbsp;of PUV was 16±2.8 months, and the mean age at enrollment was 70.6±53.5 months. The condition was detected antenatally in&nbsp;5 (10.9%) subjects only. At the time of data collection, the mean height and weight standard deviation scores were ?1.7 and ?1.5,&nbsp;respectively. Hypertension was present in 29% of patients. 44.5% of subjects had moderate-to-severe malnutrition and 42.2% had&nbsp;short stature. Mean GFR of the subjects was 66.3 ml/min/1.73m². Bilateral hydronephrosis was present on ultrasound in 26 (57.8%)&nbsp;subjects. Mean anteroposterior diameter on ultrasound was 22.1 mm for the right kidney and 20.8 mm for the left kidney. Significant&nbsp;post-void residue was detected in 54.6% of patients. Bilateral reflux was seen in 21.7% of subjects on micturating cystourethrogram.&nbsp;Urodynamic studies were available for 16 patients, and 31.3% had significant post-void residual urine. Detrusor instability was&nbsp;present in 18.8% of subjects. 35.6% of subjects underwent valve fulguration alone as the surgical procedure while 19 (42.2%) had&nbsp;a diversion procedure&nbsp; (vesicostomy/ureterostomy) along with valve fulguration. Conclusions: Most of the patients with PUV arestill diagnosed postnatally and have significant renal damage at presentation. Urinary diversion procedures are required in almost&nbsp;half of these patients. All these contribute to a poor long-term outcome.

Endocrine manifestations in children with Williams-Beuren syndrome.

Endocrine abnormalities in Williams-Beuren syndrome (WBS) include growth retardation, precocious puberty, hypercalcaemia and thyroid disorders. We aimed to characterise these abnormalities in a national cohort of children with WBS. A retrospective study comprising a national cohort of individuals with WBS in Israel (16 males, 18 females) followed between 2010 and 2016. The age at diagnosis of WBS was 1.4±1.0years. Height standard deviation score (SDS) at last visit was correlated with the midparental height SDS (r=0.46 p=0.007). Yet, participants did not reach their midparental height, with a difference of 1.40±0.85SD (p<0.001). Short stature below the 3rd percentile was found in 14 participants (41%). Mean insulin-like growth factor 1 SDS was low (-0.61±1.64) and was correlated with the mean height SDS (r=0.63 p=0.038). Two participants were diagnosed with growth hormone deficiency, and initiation of growth hormone treatment improved their height velocity. A total of eight participants (23.5%) had mild hypercalcaemia, five girls (14.7%) had precocious puberty and five participants (14.7%) had thyroid abnormalities. Individuals with WBS had a distinct growth pattern consisting of growth restriction at all ages, resulting in final adult height in the low-normal range. Precocious puberty, hypercalcaemia and thyroid abnormalities should be screened for and treated as needed.

Efficacy and safety of growth hormone treatment in Japanese children with small-for-gestational-age short stature in accordance with Japanese guidelines.

.The efficacy and safety of recombinant human GH (rhGH) treatment were assessed in Japanese children with small-for-gestational-age short stature. A total of 88 patients were enrolled in the comparative and extension studies. At the end of the comparative study (24 mo), the mean height SD score for chronological age had significantly increased in the 0.23 mg/kg/wk and 0.47 mg/kg/wk groups with increments of 0.84 ± 0.42 and 1.50 ± 0.44 SD, respectively. In the extension study, the dose could be increased based on the pre-defined growth criteria. Increments in height SD scores over the 24 to 36 mo period at doses of 0.23 mg/kg/wk, 0.23 to 0.47 mg/kg/wk, and 0.47 mg/kg/wk were 0.25 ± 0.28, 0.46 ± 0.21, and 0.28 ± 0.16 SD, respectively. The growth effect increased following dose escalation even in the low responders in the initial 2-yr treatment at 0.23 mg/kg/wk, indicating the effectiveness of dose escalation in accordance with the Japanese guidelines. rhGH at 0.47 mg/kg/wk provided a greater degree of growth promotion after 24 mo. The safety profile appeared to be tolerable and was similar in all groups. Considering the increased insulin resistance, the recommendations of the regulatory authorities should be followed to minimize the risks of rhGH treatment.

Long-term outcome of congenital nephrotic syndrome after kidney transplantation in Japan.

Congenital nephrotic syndrome is difficult to manage, particularly the Finnish type (CNF), with patients experiencing severe edema, sepsis and thrombosis before kidney transplantation. Further, nephrosis and thrombosis remain problematic after transplantation. Of 22 CNF patients managed at our hospital, 14 who underwent kidney transplantation were retrospectively studied. CNF was diagnosed according to standard criteria. The study population consisted of 3 males and 11 females. Mean gestation period was 36 ± 1.4weeks and mean birth weight was 2442 ± 454g (mean placenta to body weight ratio: 0.4). All patients started dialysis at 2.4 ± 1.3years and underwent kidney transplantation at 5.2 ± 2.0years. The kidneys were donated by the parents (n = 13), and cadaver (n = 2), including overlap. Mean follow-up period after transplantation was 14.3 ± 8.9years, and mean age at last observation was 19.5 ± 8.5years. Two patients had recurrent proteinuria after kidney transplantation; one underwent retransplantation following graft failure and eventually required dialysis, while the second had complete remission after intensive immunosuppressive therapy. There were no cases of thrombosis or serious infections. Mean eGFR at the time of last observation was 57.3 ± 16.5ml/min/1.73m2, while mean height SD score was - 2.1 ± 0.9at the time of transplantation and - 1.5 ± 1.5 at last observation. Long-term outcome in these 14 CNF patients showed satisfactory graft survival, improved height SD score, and favorable development. Although recurrent proteinuria after transplant was not predictive, it was associated with graft survival rate.

Clinical and Genetic Findings of Turkish Hypophosphatasia Cases.

Objective:Hypophosphatasia (HPP) is a rare, commonly unrecognized hereditary mineralization defect with a dramatically poor prognosis in severe cases. This study is the first to examine the detailed clinical and laboratory characteristics of patients with HPP and healthy carriers in Turkey.Methods:The study data were obtained retrospectively from the files of 10 healthy carriers and of 16 cases with HPP (12 children and 4 adults) who were followed in our center from 2012 to 2016.Results:The annual incidence of perinatal lethal hypophosphatasia (PLH) was estimated to be approximately 1 case per 435,517 live births,, which is the first report from Turkey. The clinical courses of the cases differed depending on the type of HPP. All of the seven cases (58.3% of all cases) with perinatal lethal form of HPP died. A need for respiratory support (p=0.001), a history of pyridoxine-dependent seizures (p=0.001), a low chest circumference measurement (p=0.017), younger age at diagnosis (p=0.029), a small head circumference at the time of presentation (p=0.042), a low arm span to height ratio (p=0.048), and a low serum alkaline phosphatase (ALP) level (p=0.042) seemed to be predicting factors for mortality. The mean height standard deviation score of the patients and those of the healthy carriers did not differ significantly (p=0.173). Different mutations were detected in nine of 14 cases (64.2%) in whom an ALPL gene mutation analysis could be performed, and five of these cases (35.7%) had novel mutations. The most common mutations were c746G>T (five alleles), c346G>A (three alleles), and c.140C>T (three alleles). In addition, the most frequently observed genotype in Turkish HPP cases was autosomal-dominant c.346G>A (p.A116T) mutations which were detected in three cases in two different families.Conclusion:Because of the respiratory problems, especially the lung hypoplasia, the clinical course is poor in cases with the perinatal lethal form of HPP. Some minor abnormalities such as mild short stature and osteopenia could be observed in asymptomatic heterozygote carriers. Laboratory findings were normal in these cases.

Patients with Duchenne muscular dystrophy are significantly shorter than those with Becker muscular dystrophy, with the higher incidence of short stature in Dp71 mutated subgroup

Duchenne and Becker muscular dystrophy (DMD/BMD) are caused by mutations in the dystrophin gene and are characterized by severe and mild progressive muscle wasting, respectively. Short stature has been reported as a feature of DMD in the Western hemisphere, but not yet confirmed in Orientals. Height of young BMD has not been fully characterized. Here, height of ambulant and steroid naive Japanese 179 DMD and 42 BMD patients between 4 and 10 years of age was retrospectively examined using height standard deviation score (SDS). The mean height SDS of DMD was −1.08 SD that was significantly smaller than normal (p < 0.001), indicating short stature of Japanese DMD. Furthermore, the mean height SDS of BMD was −0.27 SD, suggesting shorter stature than normal. Remarkably, the mean height SDS of DMD was significantly smaller than that of BMD (p < 0.0001). In DMD higher incidence of short stature (height SDS < −2.5 SD) was observed in Dp71 subgroup having mutations in dystrophin exons 63–79 than others having mutations in exons 1–62 (27.8% vs. 7.5%, p = 0.017). These suggested that height is influenced by dystrophin in not only DMD but also BMD and that dystrophin Dp71 has a role in height regulation.

Prenatal markers and longitudinal follow-up in simple and complex gastroschisis

ObjectiveWe aimed to identify gestational-age corrected prenatal ultrasound markers of complex gastroschisis, and to compare physical growth and neurodevelopment between children with simple and complex gastroschisis.DesignWe included prenatally diagnosed gastroschisis...

Testosterone Therapy Improves the First Year Height Velocity in Adolescent Boys with Constitutional Delay of Growth and Puberty.

BackgroundConstitutional delay of growth and puberty (CDGP) can cause significant psychological distress in adolescent boys. Although testosterone usage in this group has not been shown to affect the final adult height, the effect on the first year height velocity has not been widely reported.ObjectivesThe aim is to determine whether testosterone treatment improves the first year height velocity in boys with CDGP when compared to boys with CDGP who go through puberty spontaneouslyMethodsRetrospective data from 23 adolescent boys with CDGP was analysed. Ten out of 23 boys (43%) received testosterone injection (testosterone enanthate, 125 mg), once every 6 weeks for 3 doses in total. Both the groups (treated and untreated) had their height, bone age and testicular volume measured at the baseline, The height velocity and final predicted adult height were compared at the end of one year between both the groups.ResultsIn the testosterone-untreated group, the mean (± SD) chronological age, bone age, height standard deviation scores (SDS) and testicular volume were 14.3 years (± 0.3),12.1 years (± 1.6), -1.9 (± 0.8) and 4.7 mL (± 1.1) respectively. Within the testosterone-treated group the mean (± SD) chronological age, bone age, height SDS and testicular volume at presentation were 14.4 years (± 0.4), 11 years (± 1.6), -2.1 SD(± 0.6) and 4.5 mL (± 1.2) respectively. The mean age of treatment with testosterone was 14.4 years (± 0.44). The mean height velocity one year after treatment was 8.4 cm/year (± 1.7) in the testosterone treated group when compared to 6.1 cm/year (± 2.1) in the patients who did not receive treatment (P = 0.01). There was no significant difference in the final predicted height between the 2 groups (P = 0.15).ConclusionsTestosterone therapy improves the first year height velocity in boys with CDGP, without influencing their final predicted height.

Growth Hormone Treatment in Children With Prader-Willi Syndrome: Three Years of Longitudinal Data in Prepubertal Children and Adult Height Data From the KIGS Database.

Longitudinal data of children with Prader-Willi syndrome (PWS) treated with genotropin were registered in the Pfizer International Growth Database (KIGS). To evaluate efficacy and safety of growth hormone (GH) treatment in a large group of children with PWS. Data registered in KIGS from 1987 to 2012. Worldwide retrospective cohort study. Patients included 522 prepubertal children treated with GH for three years and 173 children who had reached adult height. Safety analysis included 2332 children. Intervention involved GH treatment. Height standard deviation score (SDS), body mass index (BMI) SDS, occurrence of serious adverse events, and deaths reported in KIGS. In prepubertal children, mean (standard deviation) height SDS improved to -0.31 (1.34) (P < 0.05) during three years of GH treatment. In the adolescent group, height SDS improved until the start of puberty to -0.22 (1.31) (P < 0.05) but had a loss of -0.77 (0.81) during puberty, resulting in a mean adult height SDS of -1.19 (1.37). Total height gain was 0.95 (1.32) SDS. BMI SDS increased in the prepubertal group from 1.11 (2.09) to 1.53 (1.43) (P < 0.05) and did not significantly change in the adolescent group, who had a BMI SDS at an adult height of 1.78 (1.26). KIGS contained 12 death reports. GH treatment in children with PWS significantly improves linear growth. BMI remains on average below +2 SDS, in contrast to the natural course of increasing obesity in PWS. Safety should be closely monitored in children with PWS, with and without GH treatment.

Growth and pubertal patterns in young survivors of childhood acute lymphoblastic leukemia.

Survivors of acute lymphoblastic leukemia (ALL) may experience endocrine dysfunction. This study evaluated growth and pubertal patterns in survivors of childhood ALL. Longitudinal assessment of anthropometric measurements and pubertal status was performed in a retrospective cohort of survivors (n=183). Median age at last endocrine visit was 16.1 years (range 8.2-27.6); median follow-up time was 8.7 years (range 3-21.4). Treatment with chemotherapy+prophylactic cranial radiation (pCRT, n=29) was associated with lower mean height standard deviation score (SDS) than chemotherapy alone (n=154) (p=0.001) and higher prevalence of adult short stature (13% vs. 2.2%). Mean age at pubertal onset was normal (girls: 10.3±1.3 years; boys: 12.0±1.3 years). Precocious puberty, diagnosed in 8.7% of patients, was more prevalent in pCRT-treated girls. Rates of overweight and obesity were 22.9% and 9.3%, respectively. Predictors of endocrine disorders were pCRT (p=0.031) and female gender (p=0.041); of obesity, higher body mass index (BMI)-SDS at diagnosis (p=0.001); and of short stature, lower height-SDS at diagnosis (p=0.038). Most childhood ALL survivors given chemotherapy alone attain normal adult height and puberty. Childhood ALL survivors are at increased risk of overweight, especially those with increased BMI at diagnosis. Clinicians should screen for overweight early in survivorship and introduce early interventions.