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.

Prednisolone oral solution plus inhaled procaterol for acute asthma in children: a double-blind randomized controlled trial.

BACKGROUND: To evaluate the efficacy of prednisolone sodium phosphate oral solution plus inhaled procaterol in the treatment of acute asthma in children. METHODS: Forty-three patients aged 6 to 12 years with an acute exacerbation of asthma were double-blind randomized into one of two treatment groups in a 1:1 ratio:1) prednisolone oral solution +placebo tablets + procaterol MDI or 2) prednisolone tablets +placebo oral solution + procaterol MDI, all given three times daily for 7 days. Peak expiratory flow rate (PEFR), 24-hour reflective asthma symptom scores, spirometry and pulmonary index score (PIS) were recorded before and after treatment. Net changes in PEFR, symptom score, PIS, Forced Expiratory Volume in the first second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75 percent of the forced vital capacity (FEF(25-75%)) (before and after treatment) and global assessment by the investigator and the subjects or their parents were analyzed. RESULTS: The two groups were statistically similar at baseline values of these parameters. After a 7-day course of treatment, the net change of PEFR before and after treatment was significantly improved in both groups, but there was no significant difference in the net change of PEFR between the two groups (57.27+/-31.44 L/min vs. 54.29 +/-30.04 L/min, difference 2.99 +/-30.76 L/min, mean +/-SD, P=0.752). The net change in PIS and total symptom score did not differ between the two groups (P=0.091 and 0.827, respectively). Similarly, the FEV1, FEV1/FVC and FEF25-75% all improved with either treatment, and neither group was significantly superior to the other group (P=0.162, 0.48 and 0.081, respectively). Global assessment by the investigator and the subjects or their parents at the end of study indicated an essentially comparable result. CONCLUSIONS: Prednisolone sodium phosphate oral solution plus inhaled procaterol is as efficacious as prednisolone tablets plus inhaled procaterol in the management of acute asthma in children.

Risk factors and characteristics of early-onset asthma in Taiwanese children.

BACKGROUND AND PURPOSE: Early-onset asthma has been reported to be associated with a family history of allergy and exposure to environmental factors. This study was designed to evaluate the relationship between age of onset of asthma and genetic and environmental factors with asthma severity in Taiwanese children. METHODS: A group of 352 children with asthma (220 males and 132 females), ranging in age from 5 to 15 years, were enrolled in this study. The subjects were divided into 2 groups: early-onset asthma (up to and including age 3) and late-onset asthma. General characteristics including family history of allergies and exposure to domestic pets and tobacco smoke were recorded. The subjects underwent pulmonary function testing and analysis of serum immunoglobulin E (IgE), eosinophil counts, and specific IgE for common allergens. RESULTS: Early-onset asthma was present in 149 subjects and late-onset asthma in 203. Family history of allergies included a sibling with asthma or urticaria predisposed to early-onset asthma (asthma, p=0.034; urticaria, p=0.024). Food and milk allergen sensitization were more common in early-onset asthma (food allergens, p=0.025; milk, p=0.034). Children with early-onset asthma had higher eosinophil counts (p=0.041). However, there was no correlation between age at onset and pulmonary function testing, the levels of total IgE and IgE specific for Dermatophagoides pteronyssinus or Dermatophagoides farinae. CONCLUSIONS: A history of asthma or urticaria in a sibling is a risk factor for early-onset asthma. A greater prevalence of food allergen sensitization and high eosinophil counts are characteristic of early-onset disease.

Buckwheat anaphylaxis: an unusual allergen in Taiwan.

IgE-mediated hypersensitivity to buckwheat is common in Korea, Japan, and some other Asian countries. However, buckwheat is not a common allergen in Taiwan. We report a woman with asthma who had anaphylactic shock, generalized urticaria, and an acute exacerbation of asthma five minutes after ingesting buckwheat. The patient underwent skin prick and Pharmacia CAP testing (Uppsala, Sweden) for specific IgE to buckwheat, white sesame and soybean as well as other common allergens in Taiwan including Dermatophagoides pteronyssinus (Dp), D. farinae (Df), cat and dog dander, cockroach, egg white, cow milk and codfish. The patient had a strongly positive skin prick test response to buckwheat and positive reactions to Dp and latex. Specific IgE results were class 6 for buckwheat, class 4 for Dp and Df, and class 2 for dog dander, wheat, sesame and soybean. Results of an open food challenge with white sesame and soybean were negative. Although buckwheat is a rare allergen in Taiwan, it can cause extremely serious reactions and should be considered in patients presenting with anaphylaxis after exposure to buckwheat.

DiGeorge syndrome associated with solitary median maxillary central incisor.

DiGeorge syndrome is a primary immunodeficiency disease characterized by dysgenesis of the thymus and parathyroid glands, conotruncal cardiac anomalies, and other dysmorphic features. Although most patients have a common microscopic deletion in chromosome 22q11.2, marked clinical variability exists. A solitary median maxillary central incisor (SMMCI) is a rare dental anomaly which may be an isolated occurrence or associated with congenital nasal airway abnormalities or holoprosencephaly. We report a patient with DiGeorge syndrome who was diagnosed at nearly 1 month of age and was later found to have a solitary median central incisor. Initially, the patient presented with recurrent episodes of respiratory distress attributed to partial airway obstruction, one of the phenotypic features of SMMCI. A fluorescence in situ hybridization study showed a chromosome 22q11.2 deletion.

Paternal mosaicism and hereditary angioedema in a Taiwanese family.

BACKGROUND: Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of localized subcutaneous or submucosal edema. It is inherited in an autosomal dominant fashion and caused by a deficiency of C1 inhibitor (C1 INH). Most patients with HAE have an absolute deficiency of C1 INH (type I HAE), whereas the rest (approximately 15%) synthesize a dysfunctional C1 INH protein (type II HAE). Mosaicism is rare in HAE. OBJECTIVE: To describe the clinical manifestations, laboratory findings, and molecular genetic studies in a Taiwanese family with type I HAE with paternal mosaicism. METHODS: A family that included a 34-year-old man (index patient) and his 25-year-old brother who both had recurrent peripheral angioedema was evaluated. A younger sister had died of an unexplained cause at 18 years of age. We analyzed blood levels of C3, C4, and C1 INH and sequenced the SERPING] (C1NH) gene that codes for C1 INH in 5 family members, including the parents and 3 brothers. RESULTS: The 4 men in the family had a novel mutation c.3_73del, p.N1fsX34 in exon 3 of the C1INH gene, resulting in C1 INH deficiency. Although the father carried this mutant gene, he had normal serum levels of C1 INH. Based on quantitative analysis of allele dosage by DNA fragment analysis (GeneScan), the father was determined to have genetic mosaicism. CONCLUSION: Parental mosaicism is a possible explanation for normal C1 INH plasma concentrations in both parents despite clinically apparent HAE in the children.

De novo mutation in the BTK gene of atypical X-linked agammaglobulinemia in a patient with recurrent pyoderma.

BACKGROUND: X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of all immunoglobulins and the absence of mature B cells, is caused by mutations in the gene encoding Bruton tyrosine kinase (BTK). Most patients have recurrent sinopulmonary infection. Infections usually occur in multiple locations across time, but single infection may be limited to one anatomic location. OBJECTIVES: To report a case of atypical XLA with recurrent pyoderma and to observe the immunologic changes in the patient in 10 years. METHODS: Immunologic investigations, skin wound culture, and molecular study with DNA sequencing were performed. RESULTS: The patient was originally diagnosed as having common variable immunodeficiency disease because of the presence of circulating B cells (CD19+ B cells: 7%) at 11 years old. On further evaluation at the age of 20 years, flow cytometric analysis of lymphocytes showed only 0.4% B cells. The molecular study with DNA sequencing of the patient showed a point mutation in complementary DNA 1630 A>G(p.R544G) in the BTK gene, indicating that the patient has XLA. The mutation analysis of the BTK gene revealed a normal DNA sequence in the other family members. CONCLUSIONS: This case is an important example of a possible presentation of XLA with a predominant skin manifestation, and it demonstrates that maintaining a high level of clinical suspicion is essential for the diagnosis of XLA in a child with recurrent pyoderma.

Systemic anaphylaxis after the ingestion of pancake contaminated with the storage mite Blomia freemani.

BACKGROUND: Systemic anaphylaxis after the ingestion of mite-contaminated food has rarely been reported. OBJECTIVE: To describe an 8-year-old boy in whom systemic anaphylaxis developed shortly after the ingestion of pancakes prepared with commercial pancake flour. METHODS: The patient underwent skin prick testing for house dust mites and with uncontaminated and mite-contaminated pancake flour. Specific IgE for mites and the main ingredients of the pancake flour were also evaluated, with titers for Der p 1, Der f 1, and Blo t 5 quantitated using immunochemical methods. A sample of pancake flour was examined microscopically for mites. RESULTS: The patient had positive skin prick test results to contaminated pancake flour extract (1 g/5 mL), Dermatophagoides pteronyssinus, and Dermatophagoides farinae but a negative skin test response to uncontaminated pancake flour. The patient's serum specific IgE analysis was positive for antibodies to dust and storage mite allergens. There was no response, however, to the main ingredients of the pancake mix. Microscopic examination of the pancake flour revealed the storage mite Blomia freemani. Using an immunochemical assay, we found that the contaminated flour contained 5.4 microg/g of the allergen Blo t 5 but no Der p 1 or Der f 1. CONCLUSIONS: This patient's anaphylactic episode was the result of ingestion of the storage mite B. freemani. To our knowledge, this is the first reported systemic hypersensitivity reaction caused by this mite anywhere in the world.