RESUMEN
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.
Asunto(s)
Diabetes Mellitus , Diabetes Mellitus/epidemiología , Diabetes Mellitus/genética , Pruebas Genéticas , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodominio , Humanos , Lactante , Insulina/genética , Proteínas de Transporte de Membrana , Mutación , Proteínas Nucleares , Fenotipo , Factores de TranscripciónRESUMEN
(IKZF1) rs4132601 and rs11978267 are common gene polymorphisms and have been associated with the risk of acute lymphoblastic leukemia. However, these associations are less evident in races and/or ethnicities other than European and Hispanic. Therefore, we investigated the association between these single-nucleotide polymorphisms and acute lymphoblastic leukemia susceptibility and disease outcome. Real-time polymerase chain reaction typing was performed for IKZF1 rs4132601 and rs11978267 for 128 pediatric acute lymphoblastic leukemia (pALL), 45 adult acute lymphoblastic leukemia (aALL), and 436 healthy controls. The G allele-containing and G-containing genotypes (GG+GT) of rs4132601 were significantly higher in pALL (P=0.003, odds ratio [OR]=1.65, 0.009, OR=1.42, respectively) and aALL (P=0.016, OR=1.81 and 0.011, OR=1.61, respectively). However, the GG haplotype was associated with the risk of pALL (P=0.044), the GA haplotype was associated with the risk of aALL (P=0.007). In aALL, the GG genotype of rs4132601 was associated with absence of remission and poor overall survival (P=0.003 and 0.041, respectively). The IKZF1 rs4132601 single-nucleotide polymorphism can be considered a susceptibility risk factor for the development of pALL and aALL in the studied cohort of Egyptian patients. The GG genotype of IKZF1 rs4132601 may be a risk factor for poor outcome in aALL patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Predisposición Genética a la Enfermedad , Factor de Transcripción Ikaros/genética , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adulto , Estudios de Casos y Controles , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
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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Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Ayuno/fisiología , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Adolescente , Glucemia/análisis , Peso Corporal , Niño , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Fructosamina/sangre , Hemoglobina Glucada/análisis , Humanos , Islamismo , Masculino , Educación del Paciente como Asunto , Pronóstico , Estudios Prospectivos , SeguridadRESUMEN
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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Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Factores de Edad , Niño , Preescolar , Diabetes Mellitus Tipo 1/diagnóstico , Egipto/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Retrospectivos , Estaciones del AñoRESUMEN
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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Densidad Ósea , Enfermedades Óseas Metabólicas/etiología , Neoplasias Óseas/secundario , Neoplasias del Sistema Nervioso/patología , Neuroblastoma/secundario , Osteoporosis/etiología , Absorciometría de Fotón , Adolescente , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/patología , Neoplasias Óseas/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Neoplasias del Sistema Nervioso/complicacionesRESUMEN
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.
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Densidad Ósea , Calcificación Fisiológica , Vértebras Lumbares/fisiopatología , Linfoma no Hodgkin/fisiopatología , Absorciometría de Fotón , Adolescente , Aminoácidos/orina , Calcitriol/sangre , Calcio/metabolismo , Niño , Preescolar , Femenino , Homeostasis , Humanos , Lactante , Vértebras Lumbares/metabolismo , Linfoma no Hodgkin/sangre , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/orina , Masculino , Estadificación de Neoplasias , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Estudios RetrospectivosRESUMEN
BACKGROUND: Patients with hemophilia may be at risk for developing reduced bone mineral density (BMD) for a number of reasons such as recurrent hemoarthrosis and immobilization. AIM OF THE WORK: To assess the BMD in children with hemophilia and to correlate BMD with findings regarding the joint disease (hemophilic arthropathy). PATIENTS AND METHODS: Thirty hemophilic patients aged 4.97 +/- 3.64 years and 30 control healthy individuals (without joint disease) aged 5.09 +/- 3.64 years were selected from the hematology unit and outpatient clinic of MUCH respectively. Anthropometric measurements were carried out in all cases. Z-score was used for weight, height, and body mass index (BMI). Joint evaluation for hemophilic patients and controls was done using Colorado PE-0.5: Half point instrument before using dual energy X-ray absorptiometry (DEXA). DEXA scanning was performed in all hemophilic patients and controls focusing on L2-L4 vertebrae. RESULTS: There was no significant difference between hemophilic patients and controls as regard anthropometric measurements and their Z-score. There was a significant difference between hemophilic patients and controls as regard BMD and BMD Z-score (mean +/- SD) (BMD: 0.48 +/- 0.13 gm/m(2) for hemophilic patients vs. 0.55 +/- 0.14 gm/m(2) for control, p = 0.05, BMD Z-score: - 0.68 +/- 0.44 for hemophilic patients vs. 0.19 +/- 0.14 for controls p = 0.003). There was a significant difference between severe hemophilic patients (factor level assay less than 1%) and controls as regard BMD and BMD Z-score (BMD: 0.41 +/- 0.15 gm/m(2) for hemophilic patients vs. 0.55 +/- 0.14 gm/m(2) for controls, p = 0.01, BND Z-score: - 1.49 +/- 0.12 for hemophilic patients vs. 0.19 +/- 0.14 for controls p = 0.001). Also, in hemophilic patients, there was an inverse significant correlation between total joint evaluation scores and BMD Z-score (r = - 0.365, p = 0.04). CONCLUSIONS: Children with hemophilia may have reduced BMD compared with age- and gender-matched controls. This reduction in BMD was independent of differences in age and body size. Children with more established hemophilic arthropathy exhibited the lowest BMD and BMD Z-score. RECOMMENDATIONS: (1) Early detection of osteopenic hemophilic children using DEXA scanning, (2) bisphosphonates plus calcium for hemophilic children with reduced BMD, (3) evaluation of the effect of on demand vs. prophylaxis replacement therapy in hemophilic patients on BMD and hemophilic arthropathy.
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Densidad Ósea , Hemartrosis/diagnóstico , Hemofilia A/complicaciones , Absorciometría de Fotón , Pesos y Medidas Corporales , Estudios de Casos y Controles , Niño , Preescolar , Egipto , Hemartrosis/fisiopatología , Hemofilia A/fisiopatología , Humanos , LactanteRESUMEN
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).