Hereditary angioedema: a Taiwanese family with a novel gene mutation.

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a deficiency of C1 esterase inhibitor (C1-INH). Affected individuals have attacks of swelling involving almost any part of the body. We studied a family with 15 living members, including a 16-year-old girl who had 3 attacks of angioedema in 2 years. Her paternal uncle had died of asphyxiation during an attack 15 years previously. We analyzed the blood of each family member for C3, C4, and C1-INH levels and sequenced the SERPING1 (formerly C1NH) gene that codes for C1-INH. Six individuals had decreased serum levels of C4 and C1-INH, and they were all found to have a single nucleotide A deletion at codon 210 of the gene, 1210fsX210, a novel mutation that accounts for the HAE in this family.

De novo mutation causing X-linked hyper-IgM syndrome: a family study in Taiwan.

X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency disorder caused by mutations of the gene encoding the CD40 ligand (CD40L). It is characterized by recurrent infections with markedly decreased serum IgG, IgA and IgE levels but normal or elevated IgM levels. We report the clinical manifestations and complete immune studies in the first family with molecularly proven XHIM in Taiwan. A 5-month-old boy presented with rapidly progressive pneumonia which responded poorly to antibiotics. High levels of IgM and very low levels of IgG, IgA, and IgE were noted in his plasma specimen: IgM, 128 mg/dl; IgG, 18 mg/dl; IgA, 4 mg/dl); IgE, 1 IU/ml. Whole blood flow cytometry when he was 21 months old showed that only a small percentage (0.48%) of his in vitro-activated CD4+ T cells expressed CD40L. When he was 3 years old, repeated flow cytometry showed essentially the same result (0.4%), compared with his father's CD40L expression of over 85%. The patient's mother had moderately decreased CD40L expression (74.4%). Hyper-IgM syndrome was confirmed by CD40L mutation analysis in the boy, which revealed a Lys 96 stop (nucleotide A307T) in exon 2 of CD40L, with a truncated protein resulting in the loss of the entire TNF domain. His mother was a carrier and apparently the individual in whom the mutation originated. Eleven other family members, including the patient's father, sister, and grandmother, and the mother's sisters and their children, all had normal results on CD40L mutation analysis. The patient has remained without significant bacterial infection on a regimen of monthly IVIG infusion and oral trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, although he has had recurrent oral ulcers and neutropenia. Bone marrow transplantation is planned.

Focal seizures as an unusual presentation of neonatal lupus erythematosus.

Neonatal lupus erythematosus is an uncommon passive autoimmune disease in which there is a transplacental passage of anti-Ro/SSA and/or anti-La/SSB maternal autoantibodies. Common clinical manifestations include cardiac disease, notably congenital heart block, cutaneous lupus lesions, hematologic disorders, and hepatobiliary disease. During the past decade, however, it has become clear that central nervous disease may also be a manifestation of neonatal lupus. We report a male neonate with the disease who had focal seizures in addition to cutaneous lupus, anemia, and thrombocytopenia. Brain ultrasound revealed normal ventricular size without a midline shift or intracranial or intraventricular hemorrhage. A brain CT showed generalized low density involving the periventricular and deep white matter. A sleep EEG revealed rare spikes axial to the right parietal lobe. The neonate had a high titer of antinuclear antibodies (1:640) with a speckled pattern, anti-Ro/SSA and anti-La/SSB antibodies, but no anti-dsDNA antibodies. He was given anti-convulsant drugs with dramatic improvement of his symptoms. One month later, a sleep EEG was normal, and he had no further seizures.