CLINICAL FEATURES AND GENETIC ANALYSIS OF SIX PATIENTS WITH WISKOTT-ALDRICH SYNDROME REPORTING TWO NOVEL MUTATIONS: EXPERIENCE OF ERCIYES UNIVERSITY, KAYSERI, TURKEY.

AIM: The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by micro-thrombocytopenia, eczema, and recurrent infections. We aimed to share our experience with six children with WAS, including two patients with two novel mutations. MATERIAL AND METHOD: We present phenotypical and laboratory description of six patients with WAS. The initial clinical presentation, biochemical and radiological features, molecular diagnosis together with long-term follow-up data are provided. RESULTS: The patients showed increased serum levels of IgE; otherwise the serum levels of IgM were decreased. The percentages of CD3+ T cells were decreased or within lower limit. Four patients underwent molecular genetics analysis and Western blot studies; two of them showed unpublished mutations: a hemizygous splice site mutation in intron 8 (c.778-2A>T), and a hemizygous deletion in exon10 of the WASP gene (c.1017delT; p.S339fsX444) were detected. Western blot studies confirmed the reduced WAS protein expression in peripheral mononuclear blood cells in four studied patients. CONCLUSIONS: The major characteristics of patients were thrombocytopenia with decreased mean platelet volume and bleeding. All patients had been previously misdiagnosed as idiopathic thrombocytopenic purpura, demonstrating the importance of a careful differential diagnosis, and intense evaluation.

PARTIAL OCULOCUTANEOUS ALBINISM AND IMMUNODEFICIENCY SYNDROMES: TEN YEARS EXPERIENCE FROM A SINGLE CENTER IN TURKEY.

BACKGROUND AND AIM: Partial oculocutaneous albinism and immunodeficiency (OCA-ID) diseases are autosomal recessive syndromes characterized by partial hypopigmentation and recurrent infections. Moreover, some OCA-ID syndromes confer susceptibility to develop a life-threatening hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH). We investigated the genetic, clinical and immunological characteristics of 20 OCA patients. MATERIAL AND METHODS: Herein, we present the clinical and immunological characteristics of 20 OCA patients who referred to the Department of Pediatric Immunology, Erciyes University Medical Faculty in Kayseri, Turkey between 2004 and 2014. RESULTS: Of the 20 OCA patients, 7 fulfilled diagnostic criteria for HLH, 9 showed defective functions of CD8 T cells and natural killer cells, and 8 received a definitive molecular diagnosis. Among the patients, we also report a patient diagnosed with two different genetic defects, in TYR and JAK3 genes, causing, respectively, OCA and ID. CONCLUSION: Our results illustrate the variability of clinical presentations and disease severity in OCA-ID patients, with consequent challenges in diagnosing and treating these patients.

Severe congenital neutropenia in two siblings related to HAX1 mutation without neurodevelopmental disorders.

Severe congenital neutropenia (SCN) is a rare primary myelopoiesis disorder, characterized by reduced absolute neutrophil counts from birth, increased susceptibility to recurrent and life-threatening infections, and a preleukemic predisposition. Herein, we describe two siblings with SCN born from consanguineous parents who were referred for complaints of recurrent cutaneous infections, gingivitis, purulent otitis media, and both lower and upper respiratory tract infections. Bone marrow aspiration of one patient demonstrated a maturation arrest in the myeloid lineage at the promyelocyte-myelocyte stages. Genetic analysis revealed a homozygous mutation in exon 2 c.130-131insA; p.W44X in the HAX1 gene. Although identical mutations were detected in both siblings, there was a clear discrepancy between the clinical course of the brother, who eventually required granulocyte colony stimulating factor (G-CSF) therapy, and the sister, who did not. Although SCN is a rare disorder, the early onset of recurrent infections and severe neutropenia, especially in children born from consanguineous parents, should always raise suspicion and warrant further evaluation.

The clinical features and genetic mutations of chronic granulomatous disease: results from a reference centre at middle Anatolia.

AIM: Chronic granulomatous disease (CGD) is a rare innate immune deficiency with neutrophil function disorder. In this retrospective study, we aimed to evaluate the clinical features of the patients with CGD. MATERIAL AND METHOD: We presented eight patients (6 boys, 2 girls) with CGD which were evaluated at Erciyes University Medical Faculty hospital between 1996 and 2012. The initial complaints, age at diagnosis, consanguinity of the parents, similar disease history or death of the siblings, physical examination, diagnostic tests, clinical courses, and genetic characteristics were analyzed. RESULTS: The initial complaints were started before the age of one in four patients; whereas only two patients diagnosed before the first birth day. Lymphadenomegally, suppurative infections, pneumonia, diarrhea were the most noted initial complaints. All parents were consanguineous. The clinical features were mild; and the ages of diagnosis were late in patients with p47 and p67 defect. The patient with X linked CGD was diagnosed when he was 3 months old; his clinical course was complicated with chronic otitis media, zygomatic abscess, lung abscess, and facial paralysis. The patient with p22 defect was diagnosed at two months of age; and gastric wall granuloma, inflammation in proximal femur was detected. CONCLUSIONS: The awareness of the clinicians about CGD will result in early diagnosis and consequently reduce the mortality and morbidity of this disease.

Four different NCF2 mutations in six families from Turkey and an overview of NCF2 gene mutations.

BACKGROUND: One of the rarest forms of autosomal recessive chronic granulomatous disease (AR-CGD) is attributable to mutations in the NCF2 gene, which encodes the polypeptide p67(phox), a key cytoplasmic protein in the phagocyte NADPH oxidase system. NCF2 is localized on chromosome 1q25, encompasses 40 kb and contains 16 exons. MATERIALS AND METHODS: We report here the clinical and molecular characterization of six patients with CGD from six consanguineous Turkish families. The ages of the five female patients were between 3 and 22 years and a male patient was 2 years old; all patients showed clear clinical symptoms of CGD. RESULTS: The mothers of the patients did not show a bimodal histogram pattern specific for X-CGD in the dihydrorhodamine-1,2,3 (DHR) assay. Moreover, p67(phox) protein expression was not detectable using flow cytometric analysis of the patients' neutrophils except in those from patient 6, which had a diminished expression. Mutation analysis of NCF2 revealed four different homozygous mutations: a novel nonsense mutation in exon 3 c.229C>T, p.Arg77X; a novel missense mutation in exon 4 c.279C>G, p.Asp93Glu; a nonsense mutation in exon 4 c.304C>T, p.Arg102X; and a novel missense mutation in exon 6 c.605C>T, p.Ala202Val. The parents were found to be heterozygotes for these mutations. CONCLUSIONS: The prevalence of NCF2 mutant families is approximately 15% in our series of 40 CGD families. This high incidence of A67 CGD in Turkey is undoubtedly caused by the high incidence of consanguineous marriages. We found three new mutations in NCF2 and one previously described. These are presented together with an overview of all NCF2 mutations now known.

An experimental evaluation of response to contrast media: Pantopaque, iopamidol, and iohexol in the subarachnoid space.

Myelography in dogs was performed with Pantopaque, iopamidol and iohexol. The effects of these agents were evaluated by histologic study of the brain, spinal cord, and meninges four months after the procedure. Retained Pantopaque was always accompanied by some degree of arachnoidal reaction, mild in the cervical cord segment and severe in the most caudal part of the cul-de-sac. No apparent protection against Pantopaque arachnoiditis was provided by either intrathecal or intramuscular methylprednisolone. We found no histologic evidence of arachnoiditis in animals examined with iopamidol and iohexol.

Cervical spinal intramedullary myxoma in childhood. Case report.

A unique case is reported of a cervical intramedullary myxoma in an 18-month-old boy who presented with torticollis and monoparesis. Radical removal of the tumor by a planned two-stage procedure was curative.

Granulomatous interstitial nephritis in extrapulmonary sarcoidosis.

Sarcoidosis is a multisystem disorder in which the lungs or intrathoracic lymph nodes are involved in more than 90% of patients with the disease. It occasionally involves kidneys most commonly due to disordered calcium metabolism. Granulomatous interstitial nephritis is a distinct renal pathology in sarcoidosis. Renal dysfunction due to granulomatous interstitial nephritis is rare. We recently encountered a sarcoidosis patient without hypercalcemia and any evidence of pulmonary involvement which is distinctly unusual.

Effects of DMSO on platelet functions and P-selectin expression during storage.

Recent studies suggested that the expression of P-Selectin on stored platelets is related to in vitro activation and loss of viability. We examined the effects of dimethylsulfoxide (DMSO) on in vitro function and P-Selectin expression of platelet concentrates. Fresh random-donor platelet units (n = 60) were divided into four equal groups. A DMSO-free group was chosen as a control. DMSO (0.5%, 1.0%, and 3.0%) was added to the other three groups. The samples were stored on a horizontal shaker at room temperature. Biochemical, morphological and platelet function tests and P-Selectin expression were monitored during storage. In all groups, P-Selectin expression, lactate and LDH levels, mean platelet volumes and PO2 increased but the aggregation response to agonist, the recovery response to hypotonic shock, platelet count, glucose level, pCO2, and HCO3 decreased during storage. In DMSO-containing groups, the P-Selectin expression which is a predictor of in vitro activation, was found significantly less often than in the DMSO-free group.

Total lymphocyte and T lymphocyte subpopulation levels in head and neck squamous cell carcinomas.

This study was performed on 72 patients with head and neck squamous cell carcinoma. Total lymphocyte, natural killer cell and total lymphocyte subpopulation levels in peripheral blood were determined and the correlation of these levels with TNM and Histopathologic Malignancy Grading (HMG) systems were investigated. TNM and HMG systems, which are two important prognostic indicators, were significantly correlated whereas total lymphocyte, natural killer cell and total lymphocyte subpopulation levels in peripheral blood had no correlation with TNM and HMG scores.

Uterine hydatid cyst.

Hydatid cyst is a parasitic disease caused by Echinococcus. Although the first and most important site for this parasite is the liver, it can be seen in pelvic organs as well. However, primary involvement is very rare. We report and discuss a case with a primary involvement of the uterus which was operated and confirmed by microscopic studies. In conclusion, the gynecologist should be aware of the possibility of hydatid cyst when a septated cystic mass is found in the pelvis.

Protective effect of magnesium supplementation on experimental 3-methyl cholanthrene-induced fibrosarcoma and changes in tissue magnesium distribution during carcinogenesis in rats.

In this study, we wanted to examine the effect of magnesium (Mg2+) supplementation on the experimental 3-methyl cholanthrene (3-MC)-induced fibrosarcoma and alterations in (Mg2+) distribution in several tissues of the rats, during carcinogenesis. It was determined that serum and tissue (Mg2+) levels of the rats in (Mg2+)-supplemented diet group were higher than those of the rats in the (Mg2+)-nonsupplemented and control groups. The mean time of fibrosarcoma development for (Mg2+)-supplemented group was longer than (Mg2+)-nonsupplemented group (p < 0.05). Symptoms of hypermagnesemia were not observed in any of the rats. These results suggests that dietary (Mg2+) supplementation may have a partial anti-carcinogenic effect on experimental 3-MC-induced fibrosarcoma by prolongation of the latent period of carcinogenesis.

Infantile Cronkhite-Canada syndrome?--Case report.

This is a case report of juvenile gastrointestinal polyposis involving the gastrointestinal system from the stomach to the rectum. Only few cases have been reported and extra-intestinal manifestations of this syndrome include macrocephaly, hepatosplenomegaly, hypotonia, clubbing of fingers, anemia and protein-losing enteropathy. The disease usually has a poor prognosis, and the children rarely live more than 2 years.

Anonychia associated with ectrodactyly syndrome: a case report.

Anonychia with ectrodactyly is a rare inherited autosomal dominant syndrome. A case of a two-month-old female infant presenting with anonychia in association with ectrodactyly and microcephaly is presented.

X-linked agammaglobulinemia and isolated growth hormone deficiency.

X-linked agammaglobulinemia and isolated growth hormone deficiency was first described in 1980 and then classified as a different primary immune deficiency. Delayed puberty in patients with X-linked agammaglobulinemia may result in delayed secretion of growth hormone (GH). To determine true isolated growth hormone deficiency. GH stimulation tests and other hypophyseal hormone evaluations must be performed. In this paper, we report a 15-year-old boy with X-linked agammaglobulinemia and isolated growth hormone deficiency, and review related literature.

Castleman's disease. A case report.

Angiofollicular lymph node hyperplasia or Castleman's Disease (CD) is a rare lymphoproliferative disorder that manifests itself as a local or generalized tumor-like condition affecting both lymph nodes and non-nodal tissues, usually in the chest and abdomen. Hyaline vascular and plasma cell types have been identified histologically. A new clinical form of CD with multisystemic involvement has been defined as multicentric Castleman's disease. It is very rare in childhood. In this paper we present an eight-year-old boy with multicentric Castleman's disease.

Virginal hypertrophy. Case report.

A 13-year-old girl with virginal hypertrophy (bilateral extensive juvenile hypertrophy) of the breasts is presented. Her breasts began to grow rapidly after puberty and reached an enormous size within a year. On examination, both breasts were greatly enlarged. Routine blood chemistry and the endocrinological investigations were normal. The computerized tomography scan of the sella was unremarkable. A bilateral reduction mammaplasty was performed, and histological analysis of the breast tissue revealed the diagnosis of virginal hypertrophy. After four months her breasts began to grow again, and a second mammaplasty was performed. After this operation, tamoxifen citrate was given to prevent recurrence for four months, and during the follow-up period of 20 months, no recurrence was noted.

Study into penetration speed during laser cutting of brain tissues.

The applications of CO2 continuous-wave lasers in neurosurgery have become important in recent years. Theoretical considerations of laser applicability in medicine are subsequently confirmed experimentally. To obtain precision operation in the laser cutting process, further theoretical developments and experimental studies need to be conducted. Consequently, in the present study, the heat transfer mechanism taking place during laser-tissue interaction is introduced using Fourier theory. The results obtained from the theoretical model are compared with the experimental results. In connection with this, an experiment is designed to measure the penetration speed during the laser cutting process. The measurement is carried out using an optical method. It is found that both results for the penetration speed obtained from the theory and experiment are in a good agreement.

Iron deficiency anemia and catecholamine metabolism.

To assess the effects of iron therapy on platelet monoamine oxidase (MAO) activity and urinary excretion of total metanephrines (MN) in infants and young children with iron deficiency anemia, 24 subjects were tested before and after one month of oral iron treatment. Thirteen healthy children comprised the control group. In the control group, platelet MAO level was 0.21 +/- 0.02 U/mg protein (mean +/- SE), urinary total metanephrine was 2.51 +/- 0.47 micrograms/mg creatinine. In cases with iron deficiency, mean platelet MAO level was 47.6% lower (p less than 0.005) whereas mean urinary metanephrine plus normetanephrine (MN-NMN) was only 20.7% lower (p greater than 0.05) than the control values. After one month, the anemic patients receiving oral iron therapy showed a significant increase in hemoglobin concentration, per cent transferrin saturation and platelet MAO activity (p less than 0.05). However, urinary metanephrine excretion was found to be lower in this group when compared to the metanephrine levels in iron deficiency before the medication (p less than 0.05). Although hemoglobin and transferrin saturation did not return to normal levels, these findings suggested that platelet MAO activity increased and urinary excretion of metanephrines decreased after iron medication.