Evaluation of the role of FTO (rs9939609) and MC4R (rs17782313) gene polymorphisms in type 1 diabetes and their relation to obesity.

OBJECTIVES: This study aims to explore the effects of fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) gene polymorphisms in children with type 1 diabetes (T1D) and their relation to obesity. METHODS: Fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) gene polymorphisms were evaluated in 164 patients and 100 controls, and genotypes, alleles, and haplotype frequencies were compared between cases and controls. RESULTS: A significant association with T1D development was found with the TC, CC, and TC+CC genotypes and the C allele of MC4R rs17782313. In addition, TA, AA, and TA+AA genotypes and the A allele of FTO rs9939609 may also be risky for T1D development. While the TC and TC+CC genotypes of MC4R rs17782313 may be protective against obesity development, the AA genotype and A allele of FTO rs9939609 may also be protective against obesity development. Regarding obese subjects, comparing diabetics vs. non-diabetic studied subjects, FTO rs9939609, TA, AA, and TA+AA genotypes and the A allele had significantly higher frequencies in T1D with a higher risk of developing T1D. However, conducting multivariable analysis using significant covariates in univariable analysis revealed that only earlier age of T1D onset, lower C-peptide, and the MC4R dominant model were considered independent predictors of obesity within T1D. CONCLUSIONS: The role of both genes' polymorphisms on the pathogenesis and the outcome of T1D and obesity can help in understanding the pathogenesis of both diseases and their associations with each other's and may be used as novel therapeutic targets for both diseases.

Conservative Approach is Safe for Perfused-Pulseless Hands Following Blunt Brachial Artery Injury in Children.

Blunt trauma of the brachial artery (BA) in pediatric age is often associated with neurological and orthopaedic injuries. Acute ischemic hands warrant immediate exploration, but the management of warm-pulseless hands following elbow trauma is controversial. This study evaluates the role of conservative treatment of blunt BA injuries in children with non-threatened hands. Eleven children with blunt trauma onto the BA having warm-pulseless hands were studied retrospectively. After a mean follow-up period of 2.5 ± 0.9 years, all cases had thorough clinical examination and duplex scan to assess the treatment outcomes. At the end of follow-up period, all subjects had well-perfused hands with intact wrist pulses. The duplex scan revealed those who had interposition grafts to be patent and one case had an aneurysmal dilatation. There was no statistical significance difference between affected and healthy forearms regarding the mean peak systolic velocity at the wrist, affected side was 62 ± 0.82 cm/s versus 68 ± 0.57 cm/s for opposite side ( p -value = 0.14). Patients with blunt BA trauma and warm-pulseless hands could be managed safely with conservative treatment, leaving surgical exploration for those who did not regain pulses after 48 hours. Duplex ultrasound can safely verify the patency of surgical repair and can be used for surveillance to detect future complications.

Assessment of bone mineral density in children with congenital cyanotic heart disease.

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.

Role of magnetic resonance diffusion weighted imaging in diagnosis of diabetic nephropathy in children living with type 1 diabetes mellitus.

OBJECTIVES: Diabetic nephropathy is a serious and a common complication of diabetes that can lead to end stage renal disease among children living with type 1 diabetes, thus an early and accurate method of diagnosis that allows timely intervention is of high importance. This study aimed to evaluate the role of magnetic resonance diffusion weighted imaging in diagnosis of diabetic nephropathy in children with type 1 diabetes. METHODS: This prospective, observational, case control study included 30 children with type 1 diabetes and 30 matched healthy controls attending the outpatient clinics in Mansoura University Children's Hospital. All were subjected to magnetic resonance DWI of the renal parenchyma and their glomerular filtration rate (GFR) was estimated, along with micro albumin in 24 h urine collection and HbA1c in patients with diabetes. RESULTS: Children with diabetes who were positive for microalbuminuria had significantly lower apparent diffusion coefficient value compared to Children with diabetes who were negative for microalbuminuria (p = 0.034) as well as controls (p = 0.001). Among children with type 1 diabetes, apparent diffusion coefficient had significant positive correlation with estimated glomerular filtration rate (r = 0.491, p = 0.006) and negative correlation with microalbuminuria (r = -0.437, p = 0.016). CONCLUSION: Magnetic resonance DWI of the renal parenchyma is correlated with estimated glomerular filtration rate (eGFR) in children with type 1 diabetes and can detect GFR deterioration even in presence of normal albumin excretion.

Genetic and clinical heterogeneity of permanent neonatal diabetes mellitus: a single tertiary centre experience.

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.

Bone Mineral Status in Children with Epilepsy: Biochemical and Radiologic Markers.

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.

Safety and metabolic impact of Ramadan fasting in children and adolescents with type 1 diabetes.

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.

Does Topical Lidocaine Reduce the Pain Associated With the Insertion of Nasal Continuous Positive Airway Pressure Prongs in Preterm Infants?: A Randomized, Controlled Pilot Trial.

OBJECTIVE: To evaluate the efficacy of topical lidocaine 2% gel in reducing the pain associated with the insertion of nasal continuous positive airway pressure (nCPAP) prongs in preterm infants. MATERIALS AND METHODS: A pilot randomized controlled trial. Sixty preterm infants, categorized into lidocaine (n=30) and control groups (n=30). The primary outcome was Premature Infant Pain Profile (PIPP) score, secondary outcomes included salivary cortisol, presence of cry, the duration of first cry, and adverse effects of lidocaine. RESULTS: There were no statistically significant differences between lidocaine and control groups regarding PIPP scores (mean±SD: 7.2±2.3 vs. 9.3±3.0, respectively, P=0.086). None of the infants in the lidocaine group had severe pain defined as a PIPP score>12, compared with 3 (10%) infants in the control group (P=0.056). Salivary cortisol concentrations were not significantly different between the lidocaine and control groups (mean±SD: 2.57±1.79 vs. 4.82±1.61 µg/dL, respectively, P=0.11). Standardized effect sizes for topical lidocaine were medium to large for reduction in PIPP scores and large for reduction in salivary cortisol (Cohen d=-0.78 and -1.32, respectively). No adverse effects were reported in infants receiving lidocaine. DISCUSSION: Our data suggest that topical lidocaine did not reduce the pain associated with the insertion of nCPAP prongs in preterm infants. However, the trends for lower PIPP scores in the lidocaine group and the effect sizes for lidocaine on PIPP scores and salivary cortisol were large enough so that a large-scale randomized clinical trial is warranted to confirm or refute our results. Such a study should compare 2 or more active pain interventions during nCPAP application, rather than evaluating a single intervention versus placebo or no treatment.

Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with obesity in Egyptian non-diabetic obese children and adolescents.

PURPOSE: To investigate the inter-relationships between adipocytokines, oxidative stress, insulin, Zn and Cu and obesity among Egyptian obese non-diabetic children and adolescents. PATIENTS AND METHODS: 72 obese children and adolescents of both sexes (5-17 years) were recruited for the study. 40 healthy normal non-obese persons of matched ages and sexes were used as control group. Lipid profile, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and leptin levels were measured. Malondialdehyde (MDA) and reduced glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were estimated. Micronutrients (Zn and Cu) concentrations in addition to insulin and fasting blood sugar (FBS) levels were also evaluated. Estimation of insulin resistance (homeostatic model assessment (HOMA-IR)) was derived from FBS measurements. RESULTS: Significant elevations (P<0.001) in TNF-α, IL-6, leptin, MDA, Cu and FBS levels and significant decreases (P<0.001) in GSH, Zn levels and SOD activity were detected among obese individuals as compared with control group. Insulin and triglyceride levels were significantly increased in obese male children and HDL-cholesterol level was increased significantly in obese adolescent females compared to controls. However, total cholesterol and LDL-cholesterol levels were significantly high in all obese cases as compared with controls. Insulin resistance was detected in 100% of the patients. CONCLUSIONS: We concluded that obesity with pro-inflammatory adipocytokines and hypozincemia together by many mechanisms participate in excessive oxidative stress and are highly associated with inflammation and the development of obesity-related complications. Obesity represents a critical risk factor for development of insulin resistance status.

Epidemiology of childhood type 1 diabetes mellitus in Nile Delta, northern Egypt - a retrospective study.

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.

Can thoracic paravertebral block replace thoracic epidural block in pediatric cardiac surgery? A randomized blinded study.

To compare the outcomes of thoracic epidural block with thoracic paravertebral block for thoracotomy in pediatric patients. A prospective double-blind study. 60 pediatric patients aged 1-24 months, ASA II, III scheduled for thoracotomy were randomly allocated into two groups. After induction of general anesthesia, thoracic epidural catheter was inserted in group E (epidural) patients and thoracic paravertebral catheter was inserted in group P (paravertebral) patients. Post operative pain score was recorded hourly for 24 hours. Plasma cortisol level was recorded at three time points. Tidal breathing analysis was done preoperatively and 6 hours postoperatively. Analgesia, serum cortisol level, and pulmonary function parameters were comparable in the two groups. However, failure rate (incorrect placement of catheter) was significantly higher in epidural group than in paravertebral group (7% versus 0%, respectively). The complications were also significantly higher in epidural group (vomiting 14.8%, urine retention 11.1% and hypotension 14.8%) than paravertebral group (0%, 0%, and 3.6%, respectively). We conclude that both thoracic paravertebral block and thoracic epidural block results in comparable pain score and pulmonary function after thoracotomy in pediatric patients; the paravertebral block is associated with significantly less failure rate and side effects.

HLA-DQB1* alleles and genetic susceptibility to type 1 diabetes mellitus.

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.

Association of CTLA-4 (+49A/G) gene polymorphism with type 1 diabetes mellitus in Egyptian children.

OBJECTIVE: To investigate the distribution of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) (+49 A/G) gene variants and the association of these variants with the clinical and laboratory findings in Egyptian children with Type-1 Diabetes (T1D). METHODS: A case control study was done for 104 Egyptian children with T1D and 78 age and sex matched healthy control. CTLA-4 (+49 A/G) gene polymorphism typing was done by PCR amplification followed by restriction fragment length polymorphism (RFLP) method. RESULTS: CTLA-4 G allele and GG homozygous genotype were significantly increased in T1D patients than in control group (P = 0.047, P = 0.048 respectively). There is no statistical difference between patient with optimal diabetic control (HbA1c < 8.5) and poor control (HbA1c ≥ 8.5) as regarding the CTLA-4 gene variant. The CTLA-4 GG genotype was statistically associated with younger age of patients (P = 0.027) and younger age of presentation (P = 0.036). Insignificant association was found between CTLA-4 alleles / genotypes and diabetic complications. CONCLUSION: The CTLA-4 +49 GG homozygous genotype is associated with T1D in Egyptian children especially with younger age of onset and in younger patients, and not associated with grades of diabetic control or diabetic complication.

Bone mineral density in newly diagnosed children with neuroblastoma.

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.

Low bone mass in children with malignant lymphoma.

The aim of this work was to study the effect of disease process on bone mass and calcium homeo-stasis in children with malignant lymphoma at diagnosis, 3 months after starting chemotherapy, and after 1 year. Evaluation of lumber vertebrae (L2-L4) bone mineral density using dual-energy X-ray absorptiometry and calcium homeostasis parameters and bone turnover biochemical markers (serum osteocalcin and urinary deoxypyridinoline) had been assayed in twenty lymphoma patients at presentation and after treatment. Low bone mass for chronological age was observed in 4 patients (20%) at diagnosis and persisted after 3 months and 1 year. Parathyroid hormone level demonstrated no differences between children with lymphoma at different stages of therapy and controls, while 25(OH) D(3) was significantly lower in lymphoma patients at different stages of therapy as compared to controls (p < .001). Osteocalcin was significantly lower in lymphoma patients at different stages of therapy. Deoxypyridinoline showed only significant higher values after 3 months of therapy compared to controls (p = .01). In conclusion, low bone mass was observed in children with lymphoma and is related to decreased osteoblastic activity and decreased mineralization of bone.

Low turnover bone disease in Egyptian children with acute leukemia.

The aim of this work was to study bone turnover markers, calcium homeostasis and bone mineral density (BMD) in children with acute leukemia at diagnosis, after induction chemotherapy, and during maintenance therapy to delineate abnormalities present. After evaluation of L2-L4 BMD using dual-energy X-ray absorptiometry in patients with acute myeloid and lymphoid leukemia at presentation and after treatment, the results were compared to 352 healthy age- and sex-matched Egyptian controls. Calcium homeostasis parameters and bone turnover biochemical markers (serum osteocalcin and urinary deoxypyridinoline) were also assayed and the results were compared to 12 healthy age- and sex-matched controls. Osteopenia was observed at diagnosis and during treatment in patients with acute leukemia. At diagnosis osteopenia was observed in 27 patients (62.8%): 10 (23.3%) had non severe osteopenia and 17 (39.5%) had severe osteopenia. This low BMD persisted in those who were followed up. Parathyroid hormone (PTH) (pg/ml) levels demonstrated non significant differences between children with acute leukemia at different stages of therapy and controls, while, 25 (OH) D3 (ng/ml) was significantly lower in acute leukemia patients at different stages of therapy compared to controls (p<0.001). Osteocalcin (ng/ml) is significantly lower in patients at different stages of the disease compared to controls (p<0.001) but there was no significant difference between patients at different stages of therapy. Deoxy-pyridoline cross links showed non-significant difference between the different types of acute leukemia and with controls. Osteopenia is a significant problem in children with acute leukemia at presentation and after chemotherapy. Osteopenia in acute leukemia appears to be of the low turnover type (decreased osteoblastic activity and decreased bone mineralization).