Wiskott-Aldrich syndrome is an X-linked combined immunodeficiency disorder characterized by severely decreased number of platelets which are small in size, eczema resembling atopic dermatitis and recurrent infection. The serum of the patient contains elevated concentrations of IgA and IgE, whereas the IgG level is usually normal and IgM level is decreased. The patients also shows skin test anergy and progressive T-lymphocytopenia. Bleedings and recurrent infections are the main causes of death and the patients usually die before age 10. Bone marrow transplantation is accepted to be the only radical therapy. We experienced a case compatible with Wiskott-Aldrich syndrome in a 5 year old male child who accompanied above clinical manifestations and laboratory findings.
Bone Marrow Transplantation ; Cause of Death ; Child ; Child, Preschool ; Dermatitis, Atopic ; Eczema ; Humans ; Immunoglobulin A ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulin M ; Male ; Skin Tests ; Thrombocytopenia ; Wiskott-Aldrich Syndrome* ; X-Linked Combined Immunodeficiency Diseases

This study represents the first epidemiological study based on the national registry of primary immunodeficiencies (PID) in Korea. Patient data were collected from 23 major hospitals. A total of 152 patients with PID (under 19 yr of age), who were observed from 2001 to 2005, have been entered in this registry. The period prevalence of PID in Korea in 2005 is 11.25 per million children. The following frequencies were found: antibody deficiencies, 53.3% (n = 81), phagocytic disorders, 28.9% (n = 44); combined immunodeficiencies, 13.2% (n = 20); and T cell deficiencies, 4.6% (n = 7). Congenital agammaglobulinemia (n = 21) and selective IgA deficiency (n = 21) were the most frequently reported antibody deficiency. Other reported deficiencies were common variable immunodeficiencies (n = 16), X-linked agammaglobulinemia (n = 15), IgG subclass deficiency (n = 4). Phagocytic disorder was mostly chronic granulomatous disease. A small number of patients with Wiskott-Aldrich syndrome, hyper-IgE syndrome, and severe combined immunodeficiency were also registered. Overall, the most common first manifestation was pneumonia. This study provides data that permit a more accurate estimation PID patients in Korea.
Adolescent ; Agammaglobulinemia/congenital/epidemiology ; Age Distribution ; Child ; Child, Preschool ; Common Variable Immunodeficiency/epidemiology ; Female ; Genetic Diseases, X-Linked/epidemiology ; Humans ; IgA Deficiency/epidemiology ; IgG Deficiency/epidemiology ; Immunologic Deficiency Syndromes/*epidemiology ; Infant ; Infant, Newborn ; Job's Syndrome/epidemiology ; Male ; Prevalence ; Questionnaires ; Registries ; Republic of Korea/epidemiology ; Severe Combined Immunodeficiency/epidemiology ; Sex Distribution ; Wiskott-Aldrich Syndrome/epidemiology ; Young Adult

OBJECTIVEWiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and an increased incidence of autoimmunity and malignancies. The patients always have a severe clinical phenotype that can result in death if not diagnosed and treated early in life. The treatment of choice with the best outcome is hematopoietic stem cell transplantation, preferably from a matched related donor. But uncertain treatment effect and high treatment cost limit its clinical application. It is the best strategy that avoiding birth of a fetus with defect through prenatal diagnosis at present. This study aimed to analyze the mutation of WASP gene in 4 Chinese families with WAS and to provide prenatal diagnosis for the high-risk fetus.

METHODThe probands of the four WAS families were all males, one of whom was deceased but had a family history and clinical datas integrated. All the patients were detected with blood routine tests, immunological tests and bone marrow examination. PCR and bilateral direct sequencing of PCR product was carried out in the regions of exon and exon-intron boundaries of WASP gene for 3 probands, 4 mothers and 100 unrelated healthy individuals as control. Prenatal diagnosis was provided for the two fetuses at the first trimester by mutation analysis.

RESULTFour WASP gene mutations were detected: c.91A > G (p.E31K), c.665C > T (p.R211X), c.397G > A (p.E133K), c.952-953delCC (p. P317fsX18), among which c.952-953delCC (p. P317fsX18) was first reported. Mothers in Family 2, 3 and 4 were carriers of WASP gene mutation, but family 1 was considered as a de-novo mutation. None of the 100 unaffected subjects had the above mutants. Prenatal diagnosis indicated that the fetus in family 2 was male and carried the same mutation as the proband, so the fetus was presumably to be a patient. The parents decided to receive an induced abortion. Following the termination of the pregnancy, the result of gene analysis of the aborted tissues was consistent with prenatal diagnosis. The fetus in family 3 was normal male confirmed by normal test results six months after birth.

CONCLUSIONThe 4 mutations of the WASP gene probably were causative to the families of WAS, among which c.952-953delCC was reported for the first time. Prenatal diagnosis by DNA sequencing is the effective method to avoid birth of WAS patient.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Fetal Diseases ; diagnosis ; Heterozygote ; Humans ; Male ; Mutation ; genetics ; Polymerase Chain Reaction ; Pregnancy ; Prenatal Diagnosis ; Sequence Analysis, DNA ; Wiskott-Aldrich Syndrome ; diagnosis ; genetics ; Wiskott-Aldrich Syndrome Protein ; genetics ; X-Linked Combined Immunodeficiency Diseases

OBJECTIVETo analyze the mutation of IL2RG gene in a Chinese family with a birth history of a dead child suspected of X-linked severe combined immunodeficiency (X-SCID), and to perform prenatal diagnosis with DNA sequencing.

METHODBlood samples of the parents of the dead child and chorionic villi at gestational age 11 weeks were collected. Eight exons comprising the open reading frame as well as their exon/intron boundaries of IL2RG gene were analyzed by PCR and bi-directional sequencing.

RESULTA heterozygous nucleotide substitution c.690C > T (R226C) in exon 5 was detected in the mother, but not in the father. In the second pregnancy of the mother, the mutation of R226C was not detected in the male fetus by prenatal diagnosis, and the heterozygous mutation was detected in the female fetus of the third pregnancy. The reliability of the prenatal genetic diagnosis was confirmed by the one-year follow-up after the neonates were born.

CONCLUSIONThe mutation of c.690C>T in IL2RG gene may be the pathologic cause of the proband with X-SCID. DNA sequencing combining sex determination is a valid strategy for prenatal diagnosis of X-SCID.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA Mutational Analysis ; DNA Primers ; Exons ; genetics ; Female ; Heterozygote ; Humans ; Infant ; Interleukin Receptor Common gamma Subunit ; genetics ; Male ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Pregnancy ; Prenatal Diagnosis ; methods ; X-Linked Combined Immunodeficiency Diseases ; diagnosis ; genetics