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 Four patients underwent molecular genetics analysis and Western blot studies; two of them showed unpublished mutations: a hemizygous splice site mutation in intron 8 (c.778-2A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.

Severe hemolytic anemia associated with Hb Volga [beta27(B9)Ala-->Asp]: GCC-->GAC at codon 27 in a Turkish family.

A boy presented at age 4 years with severe congenital hemolytic anemia characterized by highly elevated reticulocyte count (30-50%) and prominent basophilic stippling. Hb had been 4 g/dL at age 7 months. The patient was on a monthly transfusion regimen up to the age of 7 years, when he underwent splenectomy. After removal of the spleen, his Hb stabilized at 11 g/dL. No abnormal pattern was detected in hemoglobin electrophoresis at pH 9 and 6. In-vitro globin synthesis revealed the presence of an abnormal beta-chain in front of the gamma-chain. The beta(A)/beta(X) ratio was 0.77 at 30 min and 0.74 at 2 hr of incubation. Molecular analysis revealed that the patient had GCC-->GAC alteration at codon 27 (beta27(B9)Ala-->Asp) causing the abnormal hemoglobin Volga. The beta-cDNA derived from the beta-Hb Volga allele could be differentiated from HbA beta-cDNA on silver-stained gel. No imbalance in the mRNA of beta(A)/beta(Hb Volga) ratio was observed.

Griscelli's Syndrome: Clinical and Immunological Features of Two Siblings.

Two siblings diagnosed with Griscelli's syndrome (GS) are presented. The clinical features were partial albinism, silvery hair and absence of giant granules in the white blood cells. The diagnosis of GS was confirmed at the ages of nine months and two months by the demonstation of irregular clumps of pigment in the hair shaft, a finding characteristic of this syndrome. The patients had hepatosplenomegaly and bone marrow examinations revealed Iymphohistiocytosis. Immunological studies revealed normal serum immunoglobulin levels and normal T and B Iymphocyte counts. Skin tests were positive for phytohemagglutinin and PPD in the first patient. Phagocytosis was studied by flow cytometry using Mo Ab (DCFH, PMA oxidative burst, Coulter) in the second sibling and it was found as normal. Splenectomy was performed in the second sibling because of excessive splenomegaly at the age of six months but she died two months later. The first sibling died at the age of 18 months because of infection. Postmortem examination of the siblings revealed Iymphohistiocytosis in the liver and spleen.

Neuroblastoma and Poland syndrome in a 15-year-old boy.

A 15-year-old boy with neuroblastoma associated with Poland syndrome is presented. He was admitted with a 2-month history of progressive back pain and a 3-day history of weakness of the lower extremities, encopresis and enuresis. On physical examination, in addition to paraplegia, absence of the pectoralis major muscle was diagnosed on the right side of his chest. A large heterogeneous mass in the right side of the thorax was revealed on computerized tomography. Neuroblastoma was diagnosed on histopathological analysis of the mass. To the authors' knowledge this is the first case of neuroblastoma associated with Poland syndrome in the literature.