First female Korean child with Coffin-Lowry syndrome: a novel variant in RPS6KA3 diagnosed by exome sequencing and a literature review

Coffin-Lowry syndrome (CLS, OMIM # 303600) is a rare X-linked disorder caused by mutations in RPS6KA3. CLS is characterized by facial dysmorphism, digit abnormalities, developmental delays, growth retardation, and progressive skeletal changes in male patients. Females with CLS are variably affected, complicating diagnosis. Here, we describe the clinical and molecular findings in a female Korean child with CLS and review the associated literature. A 5-year-old girl presented with short stature and developmental delays. She had a coarse facial appearance characterized by a prominent forehead, hypertelorism, thick lips, and hypodontia. She also had puffy tapering fingers and pectus excavatum. We performed exome sequencing and identified a novel, likely pathogenic, heterozygous variant, c.326_338delinsCTCGAGAC (p.Val109Alafs*10), in RPS6KA3 (NM_004586.2). This is the first Korean female genetically diagnosed with CLS. In contrast to the delayed bone age reported in previous studies, our patient showed advanced bone age and central precocious puberty. CLS should be considered as a differential diagnosis of short stature, tapering fingers, and developmental delay. We suggest that molecular techniques can be a useful tool for diagnosis of rare disorders such as CLS because such conditions are not simple, and the associated spectrum of phenotypes can vary.

Clinical and molecular characterization of Korean children with infantile and late-onset Pompe disease: 10 years of experience with enzyme replacement therapy at a single center / 소아과

PURPOSE: Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase resulting from pathogenic GAA variants. This study describes the clinical features, genotypes, changes before and after enzyme replacement therapy (ERT), and long-term outcomes in patients with infantile-onset PD (IOPD) and late-onset PD (LOPD) at a tertiary medical center. METHODS: The medical records of 5 Korean patients (2 male, 3 female patients) diagnosed with PD between 2002 and 2013 at Samsung Medical Center in Seoul, Republic of Korea were retrospectively reviewed for data, including clinical and genetic characteristics at diagnosis and clinical course after ERT. RESULTS: Common initial symptoms included hypotonia, cyanosis, and tachycardia in patients with IOPD and limb girdle weakness in patients with LOPD. Electrocardiography at diagnosis revealed hypertrophic cardiomyopathy in all patients with IOPD who showed a stable disease course during a median follow-up period of 10 years. Patients with LOPD showed improved hepatomegaly and liver transaminase level after ERT. CONCLUSION: As ERT is effective for treatment of PD, early identification of this disease is very important. Thus, patients with IOPD should be considered candidates for clinical trials of new drugs in the future.

Sensitization in children with atopic dermatitis: a single center study

PURPOSE: There are few recent data regarding allergic sensitization of atopic dermatitis (AD) in Korea. The aim of this study was to investigate patterns of sensitization according to age and gender in children with AD. METHODS: This retrospective study included 4,661 children with AD from 1998 to 2014. The serum specific IgE (sIgE) levels to egg white (EW), cow's milk (CM), peanut, wheat, soybean, buckwheat, tree nuts, crustaceans, meat, and house dust mites (HDMs) were reviewed. AD was categorized into the extrinsic (ADe) and intrinsic type (ADi) according to the presence or absence of sensitization. The proportion of patients with sIgE to EW or CM greater than the previously reported diagnostic decision point (DDP) was determined. RESULTS: A total of 4,661 children (2,843 boys and 1,818 girls) were collected. We identified 1,857 of 2,663 children (69.7%) with the ADe type and 806 of 2,663 children (30.3%) with the ADi type. The sensitization rates increased with age (P<0.001). EW (59.3%) was the most commonly sensitized food, followed by CM (46.6%), peanut (32.2%), wheat (31.5%), soybean (28.1%), and buckwheat (23.7%). The most commonly sensitized food groups were tree nuts (56.7%) and crustaceans (28.3%). The rate of sensitization to HDMs was 40.1%. In addition, 11.1% and 7.5% of children had levels of sIgE to EW and CM, respectively, higher than the DDP. CONCLUSION: The incidence of ADe among children with AD was 69.7% and increased with age. The most commonly sensitized food allergen was EW, followed by CM and peanut.