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ETV6/RUNX1 (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL). Sixty-three patients were enrolled in this study to explore the distribution of this gene in Iranian population. This study used 63 peripheral blood and bone marrow (PB/BM) samples from children with ALL. Immunophenotyping of PB and BM samples were performed using flow cytometry to illustrate the lineage. Moreover, reverse transcriptase polymerase chain reaction (RT-PCR) technique was used to amplify transcripts of leukemia-specific chromosome fusion gene ETV6/RUNX1 and to monitor the expression levels of the ETV6/RUNX1 in patients according to Van Dongen et al protocol. On the basis of French-American-British (FAB) classification, 47 individuals had ALL-L1. The incidence of ETV6/RUNX1 fusion gene in this study was 34.9%. The laboratory and clinical features of twenty two ETV6/RUNX1 positive ALL cases were similar to those of other studies. The most positive cases of ETV6/RUNX1 fusion gene had the early pre B ALL and pre B ALL immunophenotypes. The ETV6/RUNX1 fusion gene is a common genetic anomaly in Iranian childhood ALL patients and the prevalence of the ETV6/RUNX1 fusion gene is similar to that of ALL patients in other countries. However early pre B cells were the most common type in studied patients.

Niemann-Pick disease and β-thalassemia are distinct conditions with specific clinical and morphological manifestations. β-thalassemia is the most common inherited blood disorder in Iran whereas Niemann-Pick disease, a lysosomal storage disorder, is rarely found in this country. This 5-month old girl, a known case of β-thalassemia major was hospitalized for failure to thrive and hepathosplenomegaly. Because of unusual splenomegaly and liver enzymes disturbance that was not compatible with the first diagnosis, further evaluation revealed cherry red spot and high lipid profile suggestive of lysosomal storage disease. Foamy cells in the bone marrow and low activity of the specific enzyme led to the diagnosis of Niemann-Pick disease. This unique case illustrates the importance of looking for a second pathological condition in a patient whose clinical profile does not support the first diagnosis in its entirety.

Vancomycin is a a glycopeptide antibiotic with bacetiocidal effects on gram positive bacteria by interfering with cell wall synthesis. The necessity for monitoring of serum vancomycin concentrations (SVCs) has been recently noticed at many institutions because of concerns for its nephrotoxicity. We aimed to describe the SVCs monitoring in pediatric patients, in an effort to determine subtherapeutic or toxic levels. The medical records were reviewed for all patients older than 60 days of age admitted to the general or subspecialty services who received intravenous vancomycin at Children''s Medical Hospital in Tehran, Iran between July 2003 and December 2005. Because pharmacokinetic parameters for children with cancer may be different, this group was evaluated separately. During the study, 167 infants and children without cancer and 42 patients with cancer; aged between 3 months to 17.5 years were treated with vancomycin for various infections. In children without cancer, peak SVCs were in an adequate therapeutic range for 93% of patients (8-55 g/ml). For children with cancer, peak SVCs was lower than 10 g/ml (10%), and trough values were lower than 5 g/ml (21%). In conclusion, according to the results of this research, due to different pharmacokinetics of vancomycin in cancerous patients, the monitoring of vancomycin plasma concentrations is necessary for the best therapeutic antibacterial activities with a fewer occurrence of serious adverse effects.

Idiopathic CD4+ Lymphocytopenia is a rare combined immunodeficiency disease, characterized by low CD4+ T-cell count and increased susceptibility to opportunistic infections, autoimmunity and malignancies after exclusion of secondary forms of CD4 lymphocytopenia. Here we present a 13-year old boy who was referred to our center because of destructive ulceration of soft and hard palates with extension to nose and maxillary sinus starting at 6 months of age. He had a history of recurrent otitis media, chronic diarrhea, arthritis and herpetic lesions of eyes and mouth since the age of 5 years. Laboratory studies revealed very low number of CD4+ T-cells (<100 cells/mm3). Secondary causes of CD4 lymphocytopenia, including HIV infection, were ruled out. Immunohistological studies of destructive lesions in oral and nasal cavity revealed angiocentric T-cell lymphoma. Unfortunately, the patient died in spite of treatment with a combination of irradiation and chemotherapy. This patient is the first reported case of lethal midline granuloma with origin T-cell lymphoma in idiopathic CD4+ lymphocytopenia.

Giant cell hepatitis (GCH) is a histological finding in infants with neonatal cholestasis and rarely can be seen after this period. Autoimmune hemolytic anemia (AIHA) which is characterized by massive and acute red blood cell destruction due to antibody production، responds favorably to corticosteroid therapy. The combination of GCH and AIHA is a rare distinct entity that carries poor response to immunosuppressive therapy and often progresses to fatal liver disease. A 13-month-old boy was referred to us with anemia and icterus. Investigations confirmed the diagnosis of GCH which was associated with AIHA. Treatment with steroids and azathioprin failed. We changed to cyclosporine. The anemia improved by steroid and IVIG at the beginning، but few months later anemia relapsed. Finally he recovered with rituximab and now he is 6 years old in suitable condition. The association of AIHA with GCH is an uncommon condition that can be life threatening. Most patients initially respond to immunosuppressive agents، but usually recur and have an aggressive course. In this case liver disease responded to steroid and immunosuppressive therapy، but the AIHA was refractory to immunosuppressive therapy. Rituximab is used in treatment of this condition، and this treatment was well tolerated and resulted in dramatic sustained improvement of anemia.

This study was designed to investigate RBC indices and HbA2 levels in parents of major beta-thalassemia patients to detect possible silent beta- thalassemia carriers and examine its potential impact on the premarital genetic counseling. This cross sectional study was performed at Children Medical Center from 2004 to 2006. After genetic counseling and getting informed consent, peripheral blood sampling was carried out on 185 carrier parents of regularly blood transfused thalassemia children. Then RBC indices and HbA2 concentration were measured. Samples with MCV and MCH higher than and/or HbA2 lower than cut off values were rechecked. In one case, MCV and MCH indices were within the limits defined for non beta- thalassemia carriers. Furthermore, four other cases were found to have decreased values of MCV and MCH but normal HbA2 levels. About 3% of beta-thalassemia carriers in our country may potentially be missed using current screening methods. Further studies are required to assess the need for presenting a new threshold for thalassemia carrier screening. Defining the causative mutations using molecular methods would pave the way for establishing a protocol for a premarital screening program in conditions when one of couples is a confirmed carrier.

Enormous diversities of heavy chain immunoglobulin (IgH) & IgK molecules are generated during B- and T-lymphocyte differentiation through the rearrangement of gene segments. Additionally, random insertion and deletion of nucleotides between gene segments make unique sequences which are cell or clone specific. IgH and IgK gene rearrangements are the most and relatively common reported rearrangements in B-precursor acute lymphoblastic leukemia, respectively. The purpose of this study is to evaluate the pattern of IgH and IgK gene rearrangements using polymerase chain reaction (PCR) in BP-ALL in Iranian children. For this prospective study, bone marrow aspirates of 183 patients with the diagnosis of acute leukemia were collected at admission before any chemotherapy. Having reviewed cytomorphology (L1:44%, L2:41%) and immunophenotyping, only 140 cases with the diagnosis of B-precursor ALL were selected. Mononuclear cells including leukemic blasts were isolated by density gradient. Having DNA extracted, hyper-variable regions of IgH and IgK were amplified by consensus primers using PCR. PCR products were analyzed after heteroduplex analysis and polyacrylamide gel electrophoresis (silver stain). The DNA sequences were compared and aligned to the sequences homologous for IgH and IgK published by Gene Bank. IgH gene rearrangements were found in 114 (90.4%) of patients using consensus primers for CDR-III and CDR-I regions (monoclonal 57.8% biclonal 34.9% oligoclonal 5.5%). Four of nine patients with T-ALL had clonal rearrangements of IgH. Clonal pattern of Igκ-Kde were present in 59 (67%) of cases (biclonal 10%). VKI (25%) and VKШ (22.7%) were the most common type of rearrangements. Clonal rearrangement pattern of IgH gene was similar to other populations. Using FRI and FRIII primers in multiplex PCR increased the rate of detection and reducing turnaround time. IgK was slightly more frequent than previous reports while VKI (25%) was the most common type.

Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia (3 males and 4 females), who experienced neutropenic periods every 3 weeks (5 with severe and 2 with moderate neutropenia), were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years (1980-2003). The range of patients’ ages was from 7 to 13 years (median 11 years). The median age at the onset of the disease was 12 months (1 month- 2 years) and the median age of diagnosis was 2 (1.5-5) years, with a median diagnosis delay of 1 year (2 months- 5 years). Neutropenia was associated with leukopenia (3 patients), anemia (3 patients), and thrombocytopenia (1 patient). Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media (6 cases), oral ulcers (5 cases), abscesses (4 cases), pneumonia (3 cases), diarrhea (3 cases), oral candidiasis (3 cases), cutaneous infections (2 cases), and periodontitis (2 cases). One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient.

Chediak – Higashi Syndrome (CHS) is a rare, primary Immunodeficiency disorder with an autosomal recessive (AR) inheritance and characterized by recurrent infection, partial occulocutaneous albinism and an accelerated phase.In this report we describe clinical and laboratory findings from 6 CHS patients. Clinical and laboratory information of six patients who were referred to our center during the last 20 years (from 1983 – 2003) were reviewed.Onset age of disease was between 3 months to 10 years. All patients had history of consanguineous parents and two patients were siblings. All patients had oculocutaneous albinism, nystagmus, recurrent infections which included upper and lower respiratory tract (U&LRT) infections, stomatitis, thrush, and skin abscesses and hepatitis. In laboratory findings, all patients had neutropenia and normal immunoglobulins and normal CD3, CD4, CD8and CD19 lymphocyte by flowcytometry and three of the four patients had chemotatic defect. Five patients certainly had giant granule in bone marrow neutrophil and in one patient it was equiovocal. Three patients had an accelerated phase, and for one patient bone marrow transplantation was done that was tolerated well and had been well after 7 years.We emphasize the need for early diagnosis on basis of characteristic facies and diagnostic laboratory examinations and early bone marrow transplantation (BMT) in patients.