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.

Hypertriglyceridemia with acute pancreatitis in a 14-year-old girl with diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is a medically fatal condition in poorly controlled hyperglycemia or newly diagnosed diabetes mellitus. Severe hypertriglyceridemia (HTG) is an uncommon complication of DKA and can be associated with acute pancreatitis (AP). We present the clinical manifestations, laboratory findings, and management of AP associated with HTG in a 14-year-old girl with DKA. The patient, with a 7-year history of type 2 diabetes presented with epigastric pain, 1 month after stopping insulin injection. DKA, severe HTG, and AP were diagnosed based on the laboratory and imaging tests. She recovered from DKA after conventional treatment for DKA, and her triglyceride (TG) level was reduced from 10,867 mg/dL to the normal range after 7 days of admission without antilipid medication. Given that her C-peptide level was not too low and considering her negative diabetes-related antibodies and high TG level, targeted gene panel sequencing was performed on the genes associated with diabetes and HTG. We identified a heterozygous mutation, c.4607C>T (p. Ala1537Val), in ABCC8 related to maturityonset diabetes of the young (MODY) 12. To our knowledge, this is the first reported case of HTG-induced AP with DKA in a patient with MODY. In addition, we reviewed the literature for pediatric cases of HTG with DKA. In patients with DKA, timely awareness of severe HTG related to insulin deficiency is crucial for improving the consequences of AP. We recommend considering AP in all DKA patients presenting with severe HTG to ensure early and proper management.

Decision support system for the prognostication of sarcopenia in adult women: Machine learning analysis using Korean National Health and Nutrition Examination Survey data

Background@#We used machine learning and population-based data for analyzing the determinants of sarcopenia in adult women and developing its decision support systems for various subgroups. @*Methods@#All data was acquired from the Korea National Health and Nutrition Examination Survey, and women 18 years and older were included in this research. The variables were selected based on female characteristics and the ability to be acquired in a survey format, and were ranked by importance using Random Forest. From this ranking, four main variables were selected, age, menopause age, menarche age and number of pregnancy. A decision supporting system was constructed based on a tree randomly selected from Random Forest. @*Results@#We defined sarcopenia as -2SD below the appendicular skeletal mass (ASM) index reference of 0.5136, and 89.87% (n = 8,610) were found non-sarcopenic and 10.13% (n = 971) were found sarcopenic. The subjects were divided into 6 groups based on menopausal status and BMI. The obese postmenopausal women had the highest number of sarcopenia, whereas the non-obese premenopausal women had the least number of sarcopenic subjects. In non-obese premenopausal women, which was considered to be at the lowest risk for sarcopenia, the most determining variable was the menarche age, followed by age and number of pregnancies. In obese and postmenopausal women, which was considered to be at the highest risk for sarcopenia, the most influential factor was the menopausal age, followed by age and menarche age. @*Conclusions@#We identified the major determinants of sarcopenia using machine learning and population-based data. This study demonstrated the strengths of the random forest as an effective decision support system for each stratified subgroup to find its own optimal cut-off points for the major variables of sarcopenia.

Nonclassic congenital lipoid adrenal hyperplasia diagnosed at 17 months in a Korean boy with normal male genitalia: emphasis on pigmentation as a diagnostic clue

Congenital lipoid adrenal hyperplasia (CLAH) is one of the most fatal conditions caused by an abnormality of adrenal and gonadal steroidogenesis. CLAH results from loss-of-function mutations of the steroidogenic acute regulatory (STAR) gene; the disease manifests with electrolyte imbalances and hyperpigmentation in neonates or young infants due to adrenocortical hormone deficiencies, and 46, XY genetic male CLAH patients can be phenotypically female. Meanwhile, some patients with STAR mutations develop hyperpigmentation and mild signs of adrenal insufficiency, such as hypoglycemia, after infancy. These patients are classified as having nonclassic CLAH (NCCLAH) caused by STAR mutations that retain partial activity of STAR. We present the case of a Korean boy with normal genitalia who was diagnosed with NCCLAH. He presented with whole-body hyperpigmentation and electrolyte abnormalities, which were noted at the age of 17 months after an episode of sepsis with peritonitis. The compound heterozygous mutations p.Gly221Ser and c.653C>T in STAR were identified by targeted gene-panel sequencing. Skin hyperpigmentation should be considered an important clue for diagnosing NCCLAH.

Association between Sleep Duration and Albuminuria in Patients with Hypertension: Korean National Health and Nutrition Examination Survey 2011–2012

BACKGROUND: Albuminuria is an indicator of renal impairment in patients with diabetes or hypertension. Studies on the effect of sleep duration on albuminuria in hypertension patients are limited. Hence, the purpose of this study was to investigate the association between sleep duration and albuminuria in Korean hypertension patients.METHODS: In this cross-sectional study, data on hypertensive patients were obtained from the fifth Korean National Health and Nutrition Examination Survey (2011–2012). Participants were classified into five groups according to self-reported sleep duration. Multiple logistic regression analyses were performed to determine the association between sleep duration and albuminuria.RESULTS: When the sleep duration was shorter than 5 hours or longer than 9 hours, the odds ratio (OR) for albuminuria was significantly higher. After adjusting for age, sex, diabetes, hemoglobin A1c, systolic blood pressure, depressive symptom, stress status, smoking status, drinking habit, triglycerides, estimated glomerular filtration rate, and body mass index, ORs (95% confidence interval) for sleep durations of ≤5 hours and ≥9 hours were 1.69 (1.14–2.51) and 2.00 (1.22–3.26), respectively.CONCLUSION: This study showed that a sleep duration of ≤5 hours or ≥9 hours was associated with the high prevalence of albuminuria in Korean hypertension patients.

Clinical Usefulness of Monitoring Cytomegalovirus-Specific Immunity by Quantiferon-CMV in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Cytomegalovirus (CMV) is a well-established cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). CD8⁺ T-cells are important for controlling CMV infection. We conducted a prospective pilot study to investigate the clinical utility of measuring the CMV-specific T-cell immune response using the QuantiFERON-CMV assay (QF-CMV) in pediatric allo-HSCT recipients. Overall, 16 of 25 (64%) patients developed CMV infection. QF-CMV was evaluated in these 16 patients during the early and late phases of the first CMV infection post allo-HSCT. Whereas the initial QF-CMV results during the early phase of CMV infection did not correlate with the course of the corresponding infection, the QF-CMV results post resolution of the first CMV infection correlated with the recurrence of CMV infection until 12 months post allo-HSCT; no recurrent infections occurred in the four QF-CMV-positive patients, while recurrent infections manifested in five of eight QF-CMV-negative (62.5%) and all three QF-CMV-indeterminate patients (P=0.019). In spite of the small number of patients examined, this study supports the potential application of monitoring CMV-specific T-cell immunity using the QF-CMV assay to predict the recurrence of CMV infection in pediatric allo-HSCT recipients.

First Report of Yokenella regensburgei Isolated from the Wound Exudate after Disarticulation Due to Diabetic Foot Infection in Korea / 대한임상미생물학회지

Yokenella regensburgei, a member of the family Enterobacteriaceae, is rarely isolated in humans. Here, we report a 71-year-old man with diabetic foot infection from which Y. regensburgei was isolated. Following debridement and disarticulation of the foot, an exudate specimen was obtained, from which Gramnegative bacilli were recovered. The organism was identified as Y. regensburgei using the Vitek 2 system (bioMerieux, USA) and 16S rRNA and gyrB gene sequencing. To our knowledge, this is the first case of Y. regensburgei isolation in Korea.

Development and Validation of Liquid Chromatography-Tandem Mass Spectrometry Method for Quantification of Plasma Metanephrines for Differential Diagnosis of Adrenal Incidentaloma

High-resolution imaging techniques have increased the detection rate of adrenal incidentaloma. We developed a method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for detection of plasma free metanephrine (MN) and normetanephrine (NMN) and evaluated its analytical performance and clinical efficacy in differential diagnosis of adrenal incidentaloma. After solid-phase extraction, chromatographic isolation of the analytes and internal standard was achieved by column elution in the LC-MS/MS system. The analytes were detected in multiple-reaction monitoring mode by using positive electrospray ionization: MN, transition m/z 180.1-->165.1; NMN, m/z 166.1-->134.1. This method was validated for linearity, precision, accuracy, lower limits of quantification and detection, extraction recovery, and the matrix effect. Plasma concentrations of MN and NMN of 14 patients with pheochromocytoma were compared with those of 17 healthy volunteers, 10 patients with essential hypertension, and 60 patients with adrenal adenoma. The assay's linear range was 0.04-50.0 and 0.08-100.0 nmol/L for MN and NMN, respectively. Assay imprecision was 1.86-7.50%. The accuracy ranged from -7.50% to 2.00%, and the mean recovery of MN and NMN was within the range 71.5-95.2%. Our LC-MS/MS method is rapid, accurate, and reliable and useful for differential diagnosis of adrenal incidentaloma.