Search

We describe a boy who presented with neonatal hypotonia, followed by delayed motor development and growth impairment. Further evaluation revealed rickets caused by proximal renal tubular dysfunction. At age 3, the boy exhibited dysmorphic features and bilateral cataract. Genetic analysis of the OCRL gene showed a novel variant in exon 13: c.1250T>A, p.Val417Asp; in silico and segregation analysis confirmed the variant to be pathogenic, compatible with the diagnosis of the oculocerebrorenal syndrome of Lowe. Lowe syndrome is a rare multisystemic disorder; the diagnostic triad requires involvement of the eye, central nervous system and the proximal renal tubule. Typical clinical features are congenital cataract, glaucoma, hypotonia, mental and behavioral problems, benign skin lesions, platelet dysfunction and dental abnormalities. Phenotypic features early in life may be nonspecific, which is illustrated by this case with a late manifestation of cataract. Because an early diagnosis can lead to better counseling and treatment, we suggest urinary testing for proteinuria as a part of the evaluation of children with unexplained hypotonia.

Case presentation We report for the first time a synchronous papillary and follicular thyroid carcinoma in a 12-year-old girl presenting with a large (5 cm diameter) left thyroid nodule, an increased left and right upper pole technetium tracer uptake at scintigraphy and hyperthyroidism. The uptake at the right lobe was explained by the crossing of the left nodule to the right site of the neck at Computed Tomography (CT) scanning. Background Although thyroid nodules are less common in children than in adults, there is more vigilance required in children because of the higher risk of malignancy. According to literature, about 5% of the thyroid nodules in adults are malignant versus 20–26% in children. The characteristics of 9 other pediatric cases with a differentiated thyroid carcinoma presenting with a toxic nodule, which have been reported during the last 20 years, are summarized. A nodular size of more than 3.5 cm and female predominance was a common finding. Conclusions The presence of hyperthyroidism in association with a hyperfunctioning thyroid nodule does not rule out thyroid cancer and warrants careful evaluation, even in the absence of cervical lymph node invasion.

Background: Physical fitness is an important determinant of quality of life (QOL) after hematopoietic stem cell transplantation. Cardiac function can influence exercise performance. The aim of this study was to assess these factors and their interrelationship. Procedure: Children underwent cardiopulmonary exercise testing (CPET) at least 1 year after hematopoietic stem cell transplantation (HSCT) and were compared with healthy controls. Systolic and diastolic heart function and left ventricle (LV) wall dimensions were measured. Health-related QOL (HR-QOL) was evaluated using PedsQL questionnaires. Results: Forty-three patients performed CPET (26 boys, 13.6 +/- 3.4 years, weight 45.5 +/- 13.3 kg, length 152.9 +/- 17.5 cm, body surface area 1.35 +/- 0.28). HSCT patients had lower maximal oxygen consumption (VO2peak/kg, 34.7 +/- 8.4 vs 46.3 +/- 7.1 mL/kg/min, P < 0.001), shorter exercise duration (9.1 +/- 2.5 vs 12.9 +/- 2.6 min, P < 0.001), and lower maximal load (%Ppeak 70.8 +/- 19.7 vs 102.4% +/- 15.9%, P < 0.001). Echocardiography demonstrated decreased interventricular septal wall thickness (interventricular septum in diastole [IVSd] Z-value -0.64 +/- 0.69, P < 0.001), and more systolic (11% of patients) and diastolic dysfunction (high E/E' Z-value 1.06 +/- 1.13, P < 0.001). LV dilatation correlates with VO2max/kg (r = -0.364, P = 0.017). HR-QOL showed lower overall and emotional functioning scores (respectively, P = 0.016 and P = 0.001). Patients after anthracycline therapy have the lowest maximal exercise performance, but have no difference in QOL. Diminished exercise performance is not encountered as a QOL limitation. Total body irradiation influences the domain of psychosocial functioning. Conclusions: LV (systolic and diastolic) and right ventricle dysfunctions justify the need for thorough cardiac follow-up in children after HSCT. Lower physical fitness levels and lower HR-QOL emphasize the importance of CPET and fitness programs.

It is of clinical importance to identify bone disease related to cystic fibrosis (CF) early in its course to allow therapeutic interventions that optimize bone health. To test the technical (precision) and clinical (percentage of abnormal results, correlation with clinical parameters) performance of a commercial quantitative ultrasound apparatus for radial measurements, speed of sound (SOS) was measured at the distal third of the left radius with the Omnisense 7000p apparatus (Sunlight Medical, Tel-Aviv, Israel) in a group of young adult CF patients with regular follow-up at the Brussels and Ghent University Hospital. Sixty-three (37 males) CF patients at a median (range) age of 23.5 y (18.1-39.9) were included. SOS, SOS z-score and SOS t-score were respectively 4017 ± 97 m/s, 20.31 ± 0.74 and 20.60 ± 0.78 in males and 4086 ± 97 m/s, 20.19 ± 0.75 and 20.51 ± 0.95 in females. Mean SOS t-score was significantly lower comparedwith the manufacturer's reference data for males (p ,0.0001) and females (p 5 0.01). SOS z- and t-scores correlated with weight z-score and body mass index z-score in females. No significant correlation was found between SOS and forced expiratory volume in 1 s (%). Neither diabetes mel- litus nor liver disease was found to influence SOS. Radial quantitative ultrasound has a precision of 0.55%. The SOS is in the low normal range in 14% of CF patients and is influenced by weight in female patients, but not by theseverityof thelungdisease. (E-mail:inge.roggen@uzbrussel.be) 2015WorldFederationforUltrasound in Medicine & Biology.

Genetic defects such as copy number variations (CNVs) in non-coding regions containing conserved non-coding elements (CNEs) outside the transcription unit of their target gene, can underlie genetic disease. An example of this is the short stature homeobox (SHOX) gene, regulated by seven CNEs located downstream and upstream of SHOX, with proven enhancer capacity in chicken limbs. CNVs of the downstream CNEs have been reported in many idiopathic short stature (ISS) cases, however, only recently have a few CNVs of the upstream enhancers been identified. Here, we set out to provide insight into: (i) the cis-regulatory role of these upstream CNEs in human cells, (ii) the prevalence of upstream CNVs in ISS, and (iii) the chromatin architecture of the SHOX cis-regulatory landscape in chicken and human cells. Firstly, luciferase assays in human U2OS cells, and 4C-seq both in chicken limb buds and human U2OS cells, demonstrated cis-regulatory enhancer capacities of the upstream CNEs. Secondly, CNVs of these upstream CNEs were found in three of 501 ISS patients. Finally, our 4C-seq interaction map of the SHOX region reveals a cis-regulatory domain spanning more than 1 Mb and harbouring putative new cis-regulatory elements, This study is supported by FWO grant G079711N (CIS-CODE). Spanish and Andalusian government grants BFU2010-14839, BFU2013-41322-P, and BIO-396 to J.L.G.S. and SAF2012-30871 to K.E.H. and S.B.S. Andalusian government supports A.F.M. as the scientific manager of the CABD´s Aquatic Vertebrates Platform. CIBERER supports S.B.S.

Maintenance of normal glucose homeostasis is crucial for survival during the perinatal period. Acylated ghrelin (AG) but not unacylated ghrelin (UAG) inhibits insulin release from pancreatic islets in adult rats. Circulating AG concentrations are low in the fetus and progressively increase in the postnatal period. We tested the hypothesis that AG has insulinostatic effects in vitro and in vivo during the perinatal period. In vitro, AG (10(-10)-10(-8) M) caused a 25-53% decrease in insulin secretion by islets from 5-d-old rat pups under normo- and hyperglycemic conditions, an effect that was mediated through the growth hormone secretagogue receptor (GHSR- 1a). Ghrelin (1-5) amide, [Dap3]-octanoyl, a pentapeptide that is resistant to deacylation and binds the GHSR-1a, had similar effects at 10(-8) M. In vivo, AG, UAG, or GHRP-6 [D-Lys3], a GHSR-1a antagonist, did not affect insulin or glucagon concentrations during the first 3 h of life. In 6-d-old pups, AG, UAG, or ghrelin (1-5) amide, [Dap3]-octanoyl did not affect glucose-induced insulin or C-peptide concentrations. In summary, AG has insulinostatic effects in vitro as early as during the perinatal period. These effects could not be confirmed in vivo, possibly due to the short half-life of AG in rat neonates.

ObjectiveGhrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader–Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.DesignA 56-week prospective, randomized, cross-over trial.MethodsNine subjects with PWS (age 14.6 (10.8–18.9) years, body mass index (BMI) Z-score +1.9 (0.6–3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period.ResultsEight subjects completed the study. Oct caused a decrease in both acylated (−53%) and desacyl (−54%) fasting ghrelin concentrations (PConclusionsOct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.

Introduction: In neonates and small infants, early diagnosis of central diabetes insipidus (CDI) and treatment with desmopressin in low doses (avoiding severe hypo- or hypernatremia) are important to prevent associated high morbidity and mortality in this particular age group. Case Presentation: We described pharmacokinetic and pharmacodynamic results of the use of recently launched oral desmopressin lyophilisate (Minirin Melt®) in two infants with CDI, diagnosed at the age of 12 and 62 days, respectively. We observed that a starting dose of 60 μg of Minirin Melt® in the first case resulted in a pharmacokinetic profile largely exceeding the reference frame observed in children with nocturnal enuresis, while a dose of 15 μg in the second case resulted in acceptable concentrations. After initial dose adjustments, administration of sublingual lyophilisate resulted in rather stable serum sodium concentrations. Conclusions: Using Minirin Melt® in infants with CDI appears to be effective, easy to use and well tolerated.

Aim: To study the relationship between insulin sensitivity and growth response in short children born small for gestational age (SGA) treated with growth hormone (GH). Methods: Randomized, open-label, 24-month intervention study in 40 short prepubertal SGA children [age (mean ± SD) 5.3 ± 1.5 years], who either remained untreated (n = 20) or were treated with GH (66 µg/kg/day; n = 20). Changes in fasting glucose, insulin, quantitative insulin sensitivity check index (QUICKI), IGF-1 and leptin after 1 and 2 years were studied. Results: Mean height SDS increased from –3.3 ± 0.7 to –2.3 ± 0.7 after 1 year, and to –1.9 ± 0.7 after 2 years of treatment. QUICKI decreased significantly (p = 0.008) in the first year of GH treatment and stabilized in the second year. Baseline QUICKI was positively associated (r = 0.40; p < 0.05) with the change in height SDS in the first year. Conclusion: Higher insulin sensitivity at the start of GH therapy is associated with greater first-year growth response to GH, and could be a promising parameter in selecting prepubertal short SGA children for GH treatment. However, this finding needs to be confirmed in larger studies.

Exocrine pancreatic insufficiency is an exceptional problem in children, mostly associated with diseases like cystic fibrosis, Shwachman-Diamond syndrome or chronic pancreatitis, as is the case in idiopathic fibrosing pancreatitis. Many viral infections are known to cause acute pancreatitis. Most of them, however, are transient with no remaining damage. The differential diagnosis of persisting diarrhoea after gastrointestinal infection does not routinely include a search for exocrine pancreatic insufficiency. Conclusion: This is the first description of a child with a transient but severe exocrine pancreatic insufficiency probably induced by an ordinary enterovirus infection

PURPOSE: Quantitative ultrasound bone sonometry (QUS) might be a promising screening method for cystic fibrosis (CF)-related bone disease, given its absence of radiation exposure, portability of the equipment and low cost.The value of axial transmission forearm QUS in detecting osteopenia in CF was therefore studied. METHODS: We investigated the application of QUS in the evaluation of bone status in a group of 64 adolescents (>12 years) and young adults (