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Children with Down syndrome (DS) exhibit higher overweight/obesity rates than their typically developing peers. Apelin-12 is a bioactive adipokine that exerts vital roles in obesity-related cardiometabolic comorbidities. To date, apelin-12 has not been investigated in obese-DS. This study aimed to explore the possible association between serum apelin-12 and obesity-related markers and to evaluate the efficiency of apelin-12 in the prediction of metabolic syndrome (MetS) in obese-DS compared to BMI Z-score matched obese-control. The cross-sectional study included 150 prepubertal children classified into three groups; obese-DS (n = 50), obese-control (n = 50), and normal-weight-control (n = 50). Anthropometric parameters, body adiposity, fasting serum levels of blood glucose (FBG), insulin, lipid profile, and apelin-12 were evaluated. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from FBG and insulin. MetS was defined using Adult Treatment Panel III criteria modified for the pediatric age group. ROC curves were analyzed to evaluate the efficiency of apelin-12 in predicting MetS in obesity groups. Obese-DS exhibited higher body adiposity with marked central fat distribution, atherogenic lipid profile, and higher HOMA-IR compared to obese-control. Apelin-12 was significantly higher in obese-DS and obese-DS with MetS compared to obese-control and obese-control with MetS respectively (p < 0.001). The increase in apelin-12 with higher obesity grades was pronounced in obese-DS. Apelin-12 strongly correlated with body adiposity, several MetS risk factors, and HOMA-IR in obese-DS. Significantly higher AUC for apelin-12 in the diagnosis of MetS among obese-DS than obese-control (AUC = 0.948 vs. AUC = 0.807; p = 0.04). CONCLUSIONS:  The current study supports the crucial role of apelin-12 in obesity-related clinical and biochemical markers and in MetS in obese-DS and obese-control. Serum apelin-12 is a potential diagnostic biomarker for MetS with greater performance in obese-DS than obese-control raising its potential for clinical and therapeutic applications. WHAT IS KNOWN: • Obese-DS children displayed excess body adiposity, Pronounced central fat distribution, atherogenic lipid profile, higher HOMA-IR, and higher prevalence of MetS than obese-control. WHAT IS NEW: • Higher serum apelin-12 was observed in obese-DS and obese-DS with MetS than obese-control and obese-control with MetS respectively. The increase in apelin-12 level with increasing obesity grades was more pronounced in obese-DS. • Apelin-12 strongly correlated with obesity-related markers and MetS components in obese-DS. Apelin-12 performed better as a diagnostic biomarker for MetS in obese-DS than obese-control.

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BACKGROUND: Cyanotic CHD is one of many disorders in paediatrics that influence the health of children in different clinical aspects. One of the fundamental aspects that may be affected is bone mineral density. OBJECTIVES: The aim of our study is to assess bone mineral density in children with congenital cyanotic heart disease of different anatomical diagnoses. DESIGN/METHODS: Cross-sectional, observational study included 39 patients (20 males) with congenital cyanotic heart disease of different anatomical diagnoses following with the cardiology clinic in Mansoura University children's hospital. All patients were subjected to anthropometric measures, oxygen saturation assessment, and lumber bone mineral density using dual-energy X-ray absorptiometry. RESULTS: Six patients (15.4%) out of the 39 included patients showed bone mineral density reduction, 13 patients (33.3%) showed bone mineral density with Z-score between -1 and -2, while 20 patients (51.3%) showed bone mineral density with Z-score more than -1. CONCLUSION: Low bone mineral density can be found in children with cyanotic CHD, making it important to consider bone mineral density assessment and early treatment if needed to avoid further complications.

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AIMS: Neonatal diabetes mellitus (NDM) is a rare disease where diabetes presents during the first six months of life. There are two types of this disorder: permanent neonatal diabetes (PNDM) and transient neonatal diabetes mellitus (TNDM). PNDM occurs due to mutations in genes involved in either beta-cell survival, insulin regulation, and secretion. This study aims to define the genetic aetiology and clinical phenotypes of PNDM in a large Egyptian cohort from a single centre. METHODS: Patients with PNDM who were diagnosed, treated, or referred for follow-up between January 2002 and January 2021 were identified and clinically phenotyped. All patients were tested for mutations in EIF2AK3, KCNJ11, ABCC8, INS, FOXP3, GATA4, GATA6, GCK, GLIS3, HNF1B, IER3IP1, PDX1, PTF1A, NEUROD1, NEUROG3, NKX2-2, RFX6, SLC2A2, SLC19A2, STAT3, WFS1, ZFP57 using targeted next-generation sequencing (NGS) panel. INSR gene mutation was tested in one patient who showed clinical features of insulin resistance. RESULTS: Twenty-nine patients from twenty-six families were diagnosed with PNDM. Pathogenic variants were identified in 17/29 patients (59%). EIF2AK3, INS, and KATP channel mutations were the commonest causes with frequency of 17%, 17%, and 14%, respectively. Patients with ABBC8 and KCNJ11 mutations were successfully shifted to sulfonylureas (SU). Paired data of glycosylated haemoglobin before and after SU transfer showed improved glycaemic control; 9.6% versus 7.1%, P = 0.041. CONCLUSIONS: PNDM is a heterogenous disease with variable genotypes and clinical phenotypes among Egyptian patients. EIF2AK3, INS, ABCC8, and KCNJ11 mutations were the commonest causes of PNDM in the study cohort. All patients with KATP channel mutations were effectively treated with glyburide, reflecting the fact that genetic testing for patients with NDM is not only important for diagnosis but also for treatment plan and prognosis.

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Vaccines are known to have side effects, most of which are tolerable. Vasculitis following vaccination is reported and has various modes of presentation. We report a 4-month-old girl presented with an unusual presentation of fulminant hepatitis, pan vasculitis, and diffuse body aneurysms following routine immunization diagnosed by echocardiography and computed tomography angiogram. It is important to be aware of different possible adverse effects following vaccines and their different modes of presentation as well as possible treatments such as intravenous immunoglobulins and high dose methylprednisolone.

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Although pubertal gynecomastia is a common clinical presentation of adolescent males, prepubertal gynecomastia is uncommon and mostly idiopathic. However, pathological causes of prepubescent gynecomastia are encountered in clinical practice. This manuscript carries an important message to general pediatricians, to care about exclusion of pathological causes for every patient of prepubertal gynecomastia. We present four different patients with pathological gynecomastia. One of them revealed to be secondary to Sertoli cell tumor, while the second patient describes trauma as a rare cause of prepubertal true gynecomastia. To the best of our knowledge, this is the first time to report occupational trauma as a cause of true gynecomastia as confirmed by pathological specimen, in a prepubertal boy. The third patient presented with retro-areolar mass and bloody nipple discharge secondary to mammary duct ectasia and had favorable self-limited course. Hyperprolactinemia secondary to neglected congenital hypothyroidism was the cause beyond gynecomastia in the fourth patient and this cause has been reported only once in the literature.Conclusion: Despite being rare, pathological causes of prepubertal gynecomastia are encountered in clinical practice, and full investigations including breast and testicular ultrasound are needed to exclude any pathology before diagnosing idiopathic gynecomastia. Repeated friction of the breast can lead to true gynecomastia not only to pseudogynecomastia as previously known. What is Known: • It has been reported that trauma can cause pseudogynecomastia due to hematoma or fat necrosis. • Prepubertal gynecomastia is mostly idiopathic. What is New: • Long-term breast trauma can cause true gynecomastia (adenosis). • Although being mostly idiopathic, pathological causes of prepubertal gynecomastia must be ruled out.

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Massage therapy (MT) improves growth parameters in preterm infants. The growth of lean mass rather than fat mass has been associated with better long-term outcomes. We aimed to study the effect of tactile/kinesthetic MT on growth and body composition parameters in preterm infants. Preterm (< 32 weeks gestation) infants were randomly assigned at corrected gestational age of 35 weeks to receive 3 consecutive, 15-min, sessions of MT over 5 days or routine care. Primary outcome was mean daily weight gain. Secondary outcomes included anthropometric measurements and body composition parameters assessed by dual X-ray absorptiometry (DXA) scan. Out of 218 infants screened, 86 were eligible and 60 infants (30 in each group) were recruited after parental consent. MT was associated with significant increase in daily weight gain [19.3 (10-34.3) versus 6.2 (2.5-18.4) g/day, p = 0.01] and growth velocity [12.5 (6-21) versus 3.6 (1.6-12.6) g/kg/d, p = 0.01] compared with routine care. Infants on MT showed significant increase in total body mass, fat mass (total/legs), lean mass (total/arms/legs/trunk), and bone mineral density (arms/legs/trunk) values compared with routine care group. In conclusions, MT improves growth quality as evident by increased total and regional lean masses, increased bone mineral density, and peripheral rather than central fat distribution. What is known on this subject? • Massage therapy (MT) for preterm infants leads to achievement of faster independent oral feeding, increased weight gain, less stress, less response to pain, less occurrence of sepsis, and shorter hospital stay. • Growth of lean mass rather than fat mass has been associated with better long-term outcomes. What this study adds? • Tactile/kinesthetic massage therapy in preterm infant is associated with improved growth parameters and anthropometric measures. • Tactile/kinesthetic massage therapy increased total body mass, fat mass (total/legs), lean mass (total/arms/legs/trunk), and bone mineral density (arms/legs/trunk) values.

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OBJECTIVE: The aim of this study is to assess bone mineral status in children with epilepsy, on different antiepileptic drugs (AEDs) regimen, using dual-energy X-ray absorptiometry (DXA) and routine biochemical bone markers. PATIENTS AND METHODS: This is observational prospective controlled cohort study, conducted at Mansoura University Children Hospital, from January 2014 to June 2015. In this study, we had 152 participants with ages 3-13 years, 70 children diagnosed with epilepsy and 82 were controls. Children classified into two groups according to the duration of treatment, Group 1 children maintained on AEDs for 6-24 months, Group 2 children ≥24 months. Bone mineral density (BMD) measured by DXA and biochemical markers includes serum calcium, phosphorus, alkaline phosphatase (ALP), and parathyroid hormone (PTH). RESULTS: In this study, we found that the serum level of calcium and phosphate were significantly low (P > 0.05) in total cases versus control. We found that the serum level of and ALP and PTH were significantly high (P > 0.05) in total cases versus control. Regarding the DXA markers, there was a significant decrease of BMD and Z-score for the total body and lumbar area in the total cases versus control (P > 0.05). CONCLUSION: The present study showed that all AEDs (new and old) affect bone mineral status in children receiving therapy for more than 6 months, altering both biochemical markers (serum calcium, phosphorus, ALP, and PTH) and radiologic markers (BMD assessed using DXA). Children on AEDs for a longer duration (≥2 years) showed more severe side effects on BMD. Children receiving multiple AEDs are more prone to altered bone mineral status, especially with long duration of therapy. The study also highlights the role of DXA as a safe noninvasive method to assess BMD in children on long-term AEDs.

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BACKGROUND: Annually, many children and adolescents with type 1 diabetes mellitus (T1DM) insist on fasting for Ramadan despite being exempted and despite knowing all the risks. We aimed to assess the safety and metabolic impact of Ramadan fasting in children with T1DM using different insulin regimens. METHODS: Children with T1DM who choose to fast during Ramadan 1434/2013 (29 days) were recruited 3 months before Ramadan. They received pre-Ramadan intensive education. Three insulin regimens were included; Regimen-I (regular insulin/NPH); Regimen-II (regular insulin/insulin glargine) and Regimen-III (premixed insulin). Changes in weight, insulin dose, HbA1c, fructosamine and lipid profile were evaluated. RESULTS: Out of total 53 patients (24 male), 28 patients (52.8%) completed Ramadan fasting (fasting group). The remaining 25 patients were included in (broke-fasting group). Positive correlation between fructosamine changes and number of days fasted during Ramadan. Significant decrease in post-Ramadan fructosamine (<0.001) and increase in post-Ramadan total cholesterol and low density lipoprotein (LDL) levels were detected within fasting, broke-fasting and insulin regimen groups. Significant higher blood glucose at three time points, pre-Iftar, pre-Sohur and midday in Regimen-I compared to Regimen-II and Regimen-III (p=0.004). CONCLUSIONS: Fasting during Ramadan is feasible and is associated with significant improvement in fructosamine level in children with T1DM using different insulin regimens. Mandatory consideration to the quality and quantity of food offered to patients with T1DM during Ramadan to guard against adverse changes in lipid profile.

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OBJECTIVES: H syndrome and pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) had been described as two autosomal recessive disorders. We aim to screen for pathogenic SLC29A3 mutations in two unrelated Egyptian families with affected siblings of these overlapping syndromes. METHODS: Clinical, laboratory, histopathological, and radiological characteristics of individuals probably diagnosed as H and/or PHID syndrome were reported. Mutation analysis of SLC29A3 gene was performed for all members of the two Egyptian families. RESULTS: All affected individuals were females; proband of family-I (A1961) displayed overlapping features of H syndrome and PHID, while her younger brother (A1962) was asymptomatic. A1961 presented with previously undescribed features; absent pectoralis major muscle and a supracondylar bony spur in left humerus. In family-II, probands (A1965 and A1966) had clinical features consistent with classical H syndrome with unique early onset of cutaneous phenomena at birth. Mutation analysis of SLC29A3 revealed homozygous mutation previously reported in literature c.1279G>A [p.G427S] in A1961 and unexpectedly in the asymptomatic A1962 of family-I. Probands of family-II were homozygous for a novel mutation c.401G>A [p.R134H], in the same codon that was published in an Indian boy [p.R134C]. CONCLUSIONS: We emphasize the inter- and intra-familial genetic heterogeneity among Egyptian patients with overlapping features of SLC29A3 disorders. This suggests the presence of other factors like regulatory genes or epigenetic factors that may explain variable disease manifestations and severity.

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OBJECTIVE: The geographical incidence of type 1 diabetes mellitus (T1DM) varies widely worldwide. Both genetic and environmental factors have been implicated, although environmental factors are still speculative and elusive. More epidemiological studies are needed to uncover such factors. To date, there are no reported studies on the epidemiology of childhood T1DM in Nile Delta, Egypt. We aimed to define the incidence, prevalence and demographic characteristics of T1DM in children (0-18 years) living in the Nile Delta region, one of the most densely populated areas in Egypt. METHODS: The study included all T1DM patients aged 0-18 years who lived in the Nile Delta region of Egypt and who were either diagnosed at or referred to Mansoura University Children's Hospital (MUCH) between 1 January 1994 and 31 December 2011. The hospital files of the patients were reviewed. General population data on the 0-18 year age group in the Nile Delta governorates were also presented. RESULTS: From a total of 1600 T1DM patients, 891 (55.7%) were females (p=0.000) and 935 (58.4%) were from rural areas (p=0.000). Calculated age-adjusted incidence of T1DM in 1996, 2006 and 2011 were 0.7, 2.0 and 3.1/10(5)/year, respectively, while calculated age-adjusted prevalence of T1DM in the same years were 1.9, 15.5 and 26.8/10(5)/year, respectively. Patients presented most frequently in the 5-10 year age group (p<0.000) and in winter months (p=0.009). CONCLUSION: In this first childhood T1DM epidemiology study in the Nile Delta region of Egypt, T1DM incidence and prevalence were found to show an increase over the past 18 years (1994-2011). Incidence and prevalence were higher in females and more cases were found to originate from rural areas.

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Sacral dimples are the most common cutaneous anomaly detected during neonatal spinal examination. Congenital dermal sinus tract, a rare type of spinal dysraphism, occurs along the midline neuraxis from occiput down to the sacral region. It is often diagnosed in the presence of a sacral dimple together with skin signs, local infection, meningitis, abscess, or abnormal neurological examination. We report a case of acute flaccid paralysis with sensory level in a 4 mo old female infant with sacral dimple, diagnosed by magnetic resonance imaging to be a paraspinal subdural abscess. Surgical exploration revealed a congenital dermal sinus tract extending from the subdural abscess down to the sacral dimple and open to the exterior with a minute opening.

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BACKGROUND: Obesity is a major worldwide health problem. It is commonly observed in Down syndrome individuals than in the general population. The reason for increased risk of obesity in DS is unclear.The current study was designed to clarify differences in some obesity- related hormones in a group of prepubertal Down syndrome children. METHODS: Thirty six Egyptian children with Down syndrome were enrolled in this study, divided according to their body mass index (BMI) into 23 obese and13 non obese. Another group of 43 non Down children were recruited, they were divided according to their BMI into 20 patients having simple obesity and 23 non obese, as control groups. Fasting blood samples were collected for estimation of fasting blood glucose (FBG), insulin, leptin, free thyroxin (FT4), thyroid stimulating hormones (TSH) and creatine kinase (CK). Insulin resistance was assessed by Homeostasis Model Assessment method (HOMA-IR). The ratio of leptin to BMI (LEP/BMI) was used as an index of leptin resistance. RESULTS: Median values of FBG, insulin, and HOMA-IR were significantly higher in Down versus non Down groups, while median values of leptin and leptin resistance were non-significantly different among Down versus non Down groups. Median TSH values were non- significantly different between obese Down and obese non Down. Although the median values of TSH and FT4 were within normal range in Down groups, four cases of subclinical hypothyroidism were encountered. Leptin levels were correlated with insulin and IR but not with TSH in Down groups. CONCLUSION: Increased circulating leptin, a marker of leptin resistance in obese children with Down syndrome seems to be similar to that in children with simple obesity. Elevated FBG and insulin in obese Down children highlights the presence of early IR. Associated myopathy evidenced by mildly elevated CK levels could be an added factor for obesity in such group of patients.

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AIM: To determine human leukocyte antigen (HLA)-DQB1 allele association with susceptibility to type 1 diabetes (T1D) and to clinical and laboratory findings. METHODS: This study was conducted on 85 unrelated Egyptian children with T1D recruited consecutively from the Pediatric Diabetes Endocrinology outpatients Clinic; Mansoura University Children's Hospital, Egypt. Patient mean follow up period was 2.5 years. Patients were subdivided according to level of HbA1c (optimal/suboptimal control < 8.5% and poor control ≥ 8.5%). The control group consisted of 113 unrelated age- and sex-matched healthy subjects without T1D or other autoimmune diseases. Genomic DNA extraction was done for all subjects using a DNA isolation kit. HLA-Class II-DQB1 allele typing was carried out with a polymerase chain reaction-sequence-specific oligonucleotide probe using a INNO-LiPA HLA-DQB1 update kit. RESULTS: Significant differences were detected between Egyptian patients with T1D and control groups in the frequencies of DQB1*02 [44.4% vs 18.6%, corrected P value (Pc) < 0.001] and DQB1*03 (41.2% vs 24.4%, Pc < 0.001). Significant differences were also observed between control groups and T1D patients in the frequencies of DQB1*05 (14.6% vs 7.2%, P = 0.029) and DQB1*06 (34.1% vs 7.2%, P < 0.001). However, after correction for multiple comparisons, the significance was retained for HLA-DQB1*06 (Pc < 0.001) but lost for HLA-DQB1*05. HLA-DQB1*0201, *0202, *030201 were positively associated with T1D (Pc = 0.014, Pc < 0.001, and Pc < 0.001 respectively), while HLA-DQB1*060101 was negatively associated (Pc < 0.001) with the condition. Although the HLA-DQB1 alleles 030101 and 050101 were significantly higher in controls (P = 0.016, P = 0.025 respectively), both of them lost statistical significance after correction of P value. The frequency of the HLA-DQB1 genotypes 02/02, 02/03, and 03/03 was higher in T1D patients, and the frequency of the genotypes 03/06, 05/06, and 06/06 was higher in controls, these differences being statistically significant before correction. After correction, the genotypes 02/02, 02/03 in T1D, and the genotypes 03/06, 06/06 in controls were still significant (Pc = 0.01, Pc < 0.001, Pc < 0.001, and Pc = 0.04, respectively). Non-significant associations were found between the frequency HLA-DQB1 alleles and genotypes in T1D in relation to the grade of diabetic control, Microalbuminuria, age, gender, age of presentation, weight, height, frequency of diabetic ketoacidosis (P = 0.42), serum cholesterol, and fasting and post-prandial level of C-peptide (P = 0.83, P = 0.9, respectively). CONCLUSION: The Current work suggests that HLA-DQB1 alleles *030201, *0202, *0201, and genotypes 02/03, 02/02 may be susceptibility risk factors for development of T1D in Egyptian children, while the HLA-DQB1*060101 allele, and 03/06, 06/06 genotypes may be protective factors. HLA-DQB1 alleles and genotypes do not contribute to microalbuminuria or grade of diabetic control.

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BACKGROUND: Higher serological prevalence rates of helicobacter pylori (H. pylori) infection have been reported in patients with type 1 diabetes (T1DM) and autoimmune thyroiditis (AT). Patients with T1DM are at increased risk for developing other autoimmune diseases, most commonly AT. It is unknown whether H. pylori infection could explain the high prevalence of thyroid autoantibodies and AT in T1DM. The aim of the current study was to evaluate anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) autoantibodies in correlation with anti-H. pylori IgG and IgA in young patients with T1DM. METHODS: Anti-H. Pylori IgG, IgA, anti-TPO and anti-Tg antibodies titers were measured in 162 euthyroid patients with T1DM and 80 healthy controls matched for age, sex and socioeconomic status. RESULTS: Seroprevalence of H. pylori was significantly higher in patients with T1DM than in healthy controls; 79% vs. 51.2%, p < 0.001. Anti H. pylori IgG was positive in 61.1% of patients with T1DM and 30% of controls, p < 0.001, anti H. pylori IgA was positive in 74% of patients with T1DM and 32.5% of controls, p < 0.001. Thyroid autoimmunity was also significantly higher in patients with T1DM than in controls; 56.7% vs. 6.2%, p < 0.001. Anti-TPO was positive in 25.3% of patients with T1DM and 3.7% of controls, p < 0.001, anti-Tg was positive in 47.5% of patients with T1DM and 6.2% of controls, p < 0.001. With simple and multiple regression analysis anti-H. pylori IgG and IgA titers were positively and significantly correlated with Anti-TPO and anti-Tg titers in patients with T1DM. CONCLUSION: our results support the idea of a connection between H. pylori infection and the occurrence of anti-TPO, anti-Tg autoantibodies and AT in young patients with T1DM. So, H. pylori infection could be considered as an environmental trigger for development of AT in T1DM. Young patients with T1DM should be screened for H. pylori infection.

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BACKGROUND: Neuroblastoma is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy which is characterized by bone metastasis. Previous reports on bone mineral density (BMD) in patients with leukemia and solid malignancies concentrate on long-term survivors and on the effect of chemotherapeutic agents and irradiation. Also, evaluation of BMD in neuroblastoma was reported in few studies which were conducted upon adult survivors of childhood cancer. Previous studies on both acute leukemia and lymphoma patients suggested that the disease process itself played a role in decrease BMD. METHODS: We evaluated 27 patients with newly diagnosed neuroblastoma for both lumbar (L2-L4) BMD and total BMD using dual energy X-ray absorptiometery (DXA) scan to highlight the effect of neuroblastoma as a disease process on BMD as this disease characterized by bone metastasis. RESULTS: Three out of the 27 patients showed low bone mass in both lumbar and total BMD studies. CONCLUSION: Low bone mass may occur in early disease process of neuroblastoma and it is important to consider BMD assessment during the early course of the disease as well as the long-term survivors as a part of the patient screening in suspected cases.

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Background. Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene mapped on chromosome 3q26.1-26.3, that codes for the glucose transporter protein 2. Methods. Two unrelated Egyptian families having suspected cases of FBS were enrolled after taking a written informed consent; both had positive consanguinity, and index cases had evidences of proximal renal tubular defects with hepatomegaly; they were subjected to history taking, signs of rickets as well as anthropometric measurements. Laboratory workup included urinalysis, renal and liver function tests including fasting and postprandial blood sugar; serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile, and detailed blood gas. Imaging including bone survey and abdominal ultrasound, and liver biopsy were done to confirm diagnosis. Molecular analysis of the GLUT2 gene was done for DNA samples extracted from peripheral blood leukocyte. All coding sequences, including flanking introns in GLUT2 gene, were amplified using PCR followed by direct sequencing. Results. Two new mutations had been detected, one in each family, in exon 3 two bases (GA) were deleted (c.253 254delGA) and in exon 6 in the second family, G-to-C substitution at position-1 of the splicing acceptor site (c.776-1G>C or IVS5-1G>A). Conclusion. FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS.

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BACKGROUND: Constitutional delay of growth and puberty (CDGP) is a variation of the onset and timing of pubertal development without a defined endocrine abnormality. Recently published studies indicate that leptin and ghrelin play a role in puberty initiation and progress. They have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that elevated ghrelin and reduced leptin concentrations could be implicated in altering the tempo of puberty in adolescents with CDGP. So in the current study we evaluate variations in leptin and ghrelin levels in adolescent boys with CDGP, the relationships between both hormones and reproductive hormones including LH, FSH and testosterone were also evaluated. METHODS: The study enrolled 23 adolescent boys with CDGP and 20 healthy controls matched for age and sex. Weight, height, BMI, testicular volume, bone age, bone age delay, serum FSH, LH, testosterone, leptin and ghrelin were assessed. RESULTS: Adolescent boys with CDGP had significantly lower leptin and higher ghrelin than normal controls. Leptin was positively correlated with BMI, bone age, testicular volume, FSH, LH and testosterone and negatively correlated with delayed bone age and ghrelin. Ghrelin was negatively correlated with BMI, bone age, testicular volume, FSH, LH and testosterone. With multiple regression analysis BMI, FSH, LH, testosterone and ghrelin remained independently correlated with leptin while BMI, LH and testosterone remained independently correlated with ghrelin. CONCLUSION: Elevated serum ghrelin and decreased leptin concentrations and their associations with reproductive hormones may explain the sexual immaturity in adolescent boys with CDGP.

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