Novel AICDA mutation in a case of autosomal recessive hyper-IgM syndrome, growth hormone deficiency and autoimmunity

BACKGROUND: The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders, which have been rarely reported to be associated with growth hormone deficiency (GHD). METHODS AND RESULTS: A nine-year-old girl with recurrent urinary tract infections, diarrhoea, sinopulmonary infections, and failure to thrive since the age of six months had normal CD3+, CD4+, CD8 + T lymphocytes, and CD19 + B lymphocytes and natural killer (NK) cells, but extremely elevated IgM and significantly decreased IgG and IgA. In view of the patient's short stature, growth hormone evaluation was carried out and growth hormone deficiency established. The patient underwent Ig replacement therapy and received growth hormone therapy in addition to antibiotics and responded well. Furthermore, the patient developed benign cervical lymphadenopathy, as well as elevated erythrocyte sedimentation rate, positive autoantibodies to SSA-Ro, and severely dry eyes, which partially responded to both the punctate occlusion and systemic corticosteroids, at the age of seven years. Sequencing analysis of the exons from activation-induced cytidine deaminase (AICDA) gene revealed that the patient was homozygous for a single T to C transversion at position 455 in exon 4, which replaces a Valine with an Alanine. CONCLUSIONS: To our knowledge, this is a new AICDA mutation, which has not been reported previously in HIGM. The mutation analysis could improve diagnosis of HIGM patients and also elaborating on the spectrum of AICDA mutations

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Novel AICDA mutation in a case of autosomal recessive hyper-IgM syndrome, growth hormone deficiency and autoimmunity.

BACKGROUND: The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders, which have been rarely reported to be associated with growth hormone deficiency (GHD). METHODS AND RESULTS: A nine-year-old girl with recurrent urinary tract infections, diarrhoea, sinopulmonary infections, and failure to thrive since the age of six months had normal CD3+, CD4+, CD8+T lymphocytes, and CD19+B lymphocytes and natural killer (NK) cells, but extremely elevated IgM and significantly decreased IgG and IgA. In view of the patient's short stature, growth hormone evaluation was carried out and growth hormone deficiency established. The patient underwent Ig replacement therapy and received growth hormone therapy in addition to antibiotics and responded well. Furthermore, the patient developed benign cervical lymphadenopathy, as well as elevated erythrocyte sedimentation rate, positive autoantibodies to SSA-Ro, and severely dry eyes, which partially responded to both the punctate occlusion and systemic corticosteroids, at the age of seven years. Sequencing analysis of the exons from activation-induced cytidine deaminase (AICDA) gene revealed that the patient was homozygous for a single T to C transversion at position 455 in exon 4, which replaces a Valine with an Alanine. CONCLUSIONS: To our knowledge, this is a new AICDA mutation, which has not been reported previously in HIGM. The mutation analysis could improve diagnosis of HIGM patients and also elaborating on the spectrum of AICDA mutations.

Association of Serum Leptin Level with Obesity in Children with Acute Lymphoblastic Leukemia.

BACKGROUND: Obesity is a medical problem in survivors of childhood acute lymphoblastic leukemia. Obesity is associated with many complications, so it is important to investigate the respective etiology. Leptin is a protein synthesized in the fatty tissue and is effective in the control of obesity. Survey of leptin in acute lymphoblastic leukemia (ALL) survivors could be helpful in controlling obesity. MATERIALS AND METHODS: In this prospective study, 53 pediatric patients diagnosed with ALL between 2006 and 2012 from Southern Iran, were enrolled. We examined body mass index (BMI) status and performed laboratory measuring tests including triglyceride, cholesterol, fasting blood sugar, leptin at diagnosis time and then every 6 months and in the last visit. RESULTS: Participants consisted of 35 male and 18 female patients. At the time of diagnosis, 5.66% were overweight or obese, whereas at the end of treatment, approximately 13 patients (24.53%) were overweight or obese. The median and interquartile range (IQR) for blood leptin level were significantly higher for obese patients than other patients (885, 1120 vs. 246, 494 pg/ml), (P=0.030). The median and IQR were also significantly higher in females than in males (861, 969 vs. 204, 267 pg/ml), (P=0.006). CONCLUSION: Obesity is a complication of ALL treatment. It is associated with elevated blood leptin level. Hypothalamus leptin resistance in obese patients should be considered. In each visit, clinicians should weight and their patient's BMI take into account.

Investigation of osteopontin levels and genomic variation of osteopontin and its receptors in Type 1 diabetes mellitus.

BACKGROUND: Failure in self-tolerance towards ß-cells in diabetes mellitus (DM) pathogenesis involves a series of complex events that are governed by environmental and genetic factors. Considering the importance of osteopontin (OPN) in T-helper-1 (Th1) cells development, the aim of this study was to evaluate the serum level and gene polymorphism of OPN in Iranian Type 1 diabetic (T1DM) children. METHODS: In this case-control study, 87 T1DM children and 86 healthy ones were enrolled. Blood samples of both groups were checked for OPN level. The single nucleotide polymorphisms (SNP) were genotyped by RFLP analysis for OPN rs1126772, its receptor integrin α4 (ITGA4) rs 1449263, and CD44 rs8193. RESULTS: Serum levels of OPN in diabetic children were significantly higher in cases compared to the control group (p=0.023), but there was no significant relationship between OPN rs1126772 (p=0.79), its receptor integrin α4 (p=0.31), and CD44 rs8193 (p=0.45), and T1DM. CONCLUSION: Higher amounts of OPN were seen in T1DM children. It is assumed that OPN might have inducing effects on T1DM development, particularly when genetically susceptible individuals are predisposed by an environmental insult. However, the 3 SNPs of OPN and its receptors did not show noticeable association with T1DM. The power of our study (~19%) was insufficient to observe any significant statistical difference between the groups; moreover, this study does not exclude the possibility of association of other SNPs of OPN and its receptors with this disease, and more studies are needed to clarify the issue.

The study of effectiveness of blended learning approach for medical training courses.

BACKGROUND: Blended learning as a method of learning that includes face to face learning, pure E-learning and didactic learning. This study aims to investigate the efficacy of medical education by this approach. METHODS: This interventional study was performed in 130 students at different clinical levels participating in class sessions on "congenital adrenal hyperplasia and ambiguous genitalia". Sampling was done gradually during 6 months and all of them filled a pretest questionnaire and received an educational compact disk. One week later, a presence class session was held in a question and answer and problem solving method. Two to four weeks later, they filled a posttest questionnaire. RESULTS: There was a significant correlation between pretest and posttest scores and the posttest scores were significantly more than the pretest ones. Sub-specialized residents had the most and the students had the least attitude towards blended learning approach. There was a significant correlation between the research samples' accessibility to computer and their attitude and satisfaction to blended learning approach. CONCLUSION: Findings generally showed that the blended learning was an effective approach in making a profound learning of academic subjects.

Serum zinc levels in children and adolescents with type-1 diabetes mellitus.

BACKGROUND: There have been very few studies, with contradictory results, on the zinc status of children and adolescents with type-1 diabetes mellitus. The objective of this cross-sectional study was to determine zinc status based on the serum zinc concentration in type-1 diabetic children and adolescents and compare it with that of healthy controls. METHODS: Thirty children and adolescents with type-1 diabetes mellitus, aged 6 to 18 years, and 30 age- and sex-matched healthy controls participated in the study. Serum zinc, fasting blood sugar, hemoglobin A(1c) and serum albumin were measured by flame atomic absorption spectrophotometry, enzymatic colorimetry, ion-exchange chromatography and colorimetry using bromocresol green methods, respectively. RESULTS: No statistically significant difference was found in the mean serum zinc concentration between diabetic patients and healthy controls (111.0 ± 3.1 and 107.1 ± 3.8 mg/dl respectively, P= 0.4). No correlations were found between the serum zinc levels and fasting blood sugar, hemoglobin A(1c), or the duration of the disease in the patients. CONCLUSION: The zinc levels of diabetic children and adolescents are not noticeably different compared to those of healthy controls and are independent of glycemic control and the duration of the disease.

Isolated growth hormone deficiency in a patient with immunoglobulin class switch recombination deficiency.

Growth hormone deficiency (GHD) may be associated with a number of immunodeficiency diseases, but its association with immunoglobulin class switch recombination (Ig CSR) deficiencies is very rare. We report the case of a patient with a history of recurrent diarrhea and respiratory infections diagnosed with hyper IgM syndrome on the basis of immunological findings (low serum levels of IgG and IgA and an elevated serum level of IgM). In view of the patient's short stature, growth hormone evaluation was performed and growth hormone deficiency confirmed. The patient received growth hormone therapy in addition to Ig replacement therapy and antibiotics and responded well. As the coding regions of the genes known to be responsible for Ig CSR (CD40L, CD40, AICDA, and UNG) were intact in our patient, this might be a new form of Ig CSR deficiency.

Selective screening of amino acid disorders in the south-west of Iran, Shiraz.

A diagnostic study of amino acid concentrations in dried blood spot samples from 1044 symptomatic children revealed high incidences of phenylketonuria, tyrosinaemias, and maple syrup urine disease in the Shiraz region of Iran. Minimum incidences, based on babies born between 1996 and 2001 inclusive, and diagnosed by the end of 2001, are 1:3672, 1:10651 and 1:21 303, respectively.