Noh ES, et al. Yonsei Med J. 2019 Oct;60(10):984-991. https://doi.org/10.3349/ymj.2019.60.10.984

Non-alcoholic fatty liver disease (NAFLD) is defined as chronic hepatic steatosis and is becoming prevalent along with the increasing trend of obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis (NASH) from simple steatosis. This study evaluates the association between the triglyceride glucose (TyG) index and the ultrasonographic fatty liver indicator (US-FLI), and the possibility of using the TyG index for prediction of severity of pediatric NAFLD. One hundred twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into 3 groups according to body mass index (BMI). Ninety two were obese, and 19 and 10 were overweight and normal weight, respectively. The homeostatic model assessment for insulin resistance (HOMA-IR) was highest in the group with obesity (P=0.044). The TyG index and US-FLI did not differ significantly among the 3 BMI groups (P=0.186). Fourteen (11.6 %) of the 121 patients had US-FLI  6, in whom the BMI-SDS and TyG index were higher (P=0.017, P=0.004), whereas HOMA-IR did not differ significantly from the group with US-FLI < 6 (P=0.366). US-FLI was associated with BMI-SDS and the TyG index. TyG index was significantly associated with US-FLI after adjustment for BMI-SDS. The cut-off value for the TyG index for predicting US-FLI  6 was 8.91, with an area under the curve of 0.785. TyG index was associated with the degree of hepatic steatosis, suggesting that it might be a useful tool for predicting the severity of pediatric NAFLD.

Background: Mucopolysaccharidosis type III (MPS III) is an autosomal recessive lysosomal storage disorder characterised by progressive neurocognitive deterioration. MPS III subtypes are clinically indistinguishable, with a wide range of symptoms and variable severity. The natural history of this disorder within an Asian population has not yet been extensively studied. This study investigated the natural history of Korean patients with MPS III. Methods: Thirty-four patients from 31 families diagnosed with MPS III from January 1997 to May 2020 in Samsung Medical Centre were enrolled. Clinical, molecular, and biochemical characteristics were retrospectively collected from the patients’ medical records and via interviews. Results: 18 patients had MPS IIIA, 14 had IIIB, and two had IIIC. Twenty (58.9%) patients were male. Mean age at symptom onset was 2.8 ± 0.8 years and at diagnosis was 6.3 ± 2.2 years. All patients with MPS IIIA and IIIB were classified into the rapidly progressing (RP) phenotype. The most common symptom at diagnosis was language retardation (88.2%), followed by motor retardation (76.5%), general retardation (64.7%), and hyperactivity (41.2%). Language retardation was more predominant in IIIA, and motor retardation was more predominant in IIIB. The mean age of the 13 deceased patients at the time of the study was 14.4 ± 4.1 years. The age at diagnosis and lag time were significantly older and longer in the non-survivor group compared with the survivor group (p = 0.029 and 0.045, respectively). Genetic analysis was performed in 24 patients with MPS III and identified seven novel variants and three hot spots. Conclusion: This study is the first to analyse the genetic and clinical characteristics of MPS III patients in Korea. Better understanding of the natural history of MPS III might allow early diagnosis and timely management of the disease and evaluation of treatment outcomes in future clinical trials for MPS III.

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.

Prader–Willi syndrome (PWS) is a rare genetic disorder characterized by an insatiable appetite that leads to morbid obesity. Previous studies reported health problems in adults with PWS. However, studies on younger adults are lacking, and there are no specific studies of endocrine and metabolic illness in this age group. We performed a retrospective cohort study of 68 individuals with PWS aged 19 to 34 years at Samsung Medical Center. The prevalence of endocrine and metabolic illnesses were compared with those in an age-, sex-, and BMI-matched healthy control group. Young adults with PWS had a higher prevalence of metabolic syndrome (35.3% vs. 4.4%), type 2 diabetes mellitus (50.0% vs. 5.4%), hypertension (30.8% vs. 16.1%), dyslipidemia (38.2% vs. 14.7%), decreased bone density (26.4% vs. 0.9%), and sleep apnea (32.3% vs. 4.4%) than controls (all p < 0.05). The PWS group that maintained recombinant human growth (rhGH) treatment in adulthood had a lower probability of having a BMI ≥ 30 at the last follow-up (odds ratio = 0.106 (0.012–0.948), p = 0.045). Endocrine and metabolic illnesses in individuals with PWS may have already started in the early teens; therefore, appropriate screening and early intervention are important. Better understanding of the natural history of PWS and age-related complications will lead to better-quality medical care for individuals with PWS.

OBJECTIVES: Hyperphagia is a highly stressful, life-threatening feature of Prader-Willi syndrome (PWS). It is important to assess this complex behavior accurately over time. This study aimed to develop and validate the Pediatric-Youth Hyperphagia Assessment for Prader-Willi syndrome (PYHAP) as a tool targeting children and adolescents.METHODS: After an extensive literature review and qualitative interviews, the final version of the PYHAP with 14 questions in 3 domains (verbal [5], behavior [4], and social [5]) was developed and tested at Samsung Medical Center in Seoul, Korea from July 2018 to September 2019. Exploratory factor analysis and confirmatory factor analysis (CFA) were performed to confirm construct validity. The correlations between the PYHAP and the Korean Children’s Eating Behavior Questionnaire (K-CEBQ) were calculated to evaluate convergent and discriminant validity. Criterion validity and the validity of the response categories were also tested.RESULTS: Cronbach’s alpha coefficient of the PYHAP was 0.91. The fit indices for CFA were good (comparative fit index, 0.87; standardized root mean squared residual, 0.08). The domains of the PYHAP were closely correlated with the relevant domains of the K-CEBQ. The accuracy of the PYHAP score for predicting uncontrolled hyperphagia was good (area under the curve, 0.75; 95% confidence interval, 0.65 to 0.85).CONCLUSIONS: The PYHAP was confirmed to be a reliable and valid tool to evaluate hyperphagia in children and adolescents with PWS via caregivers’ assessments. It is recommended to use the PYHAP to communicate with parents or caregivers about patients’ hyperphagia or to monitor and manage extreme behaviors in children with PWS.