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Background@#and PurposeEpilepsy increases the risk of death in affected individuals of any age. We aimed to determine the mortality caused by epilepsy and its time trends in Korea. @*Methods@#We obtained population and cause of death data between 1993 and 2019 from Statistics Korea. We identified death caused by epilepsy or status epilepticus. We calculated the crude mortality rate (CMR), age-specific mortality rate, age-standardized mortality rate (ASMR, corresponding to epilepsy-related deaths per 100,000 persons in the general population), and the proportional mortality (PM, corresponding to the proportion of epilepsy-related deaths among all-cause deaths). @*Results@#In 2019, 471 deaths were caused by epilepsy (CMR=0.92), accounting for 0.16% of all deaths in that year. The age-specific mortality rate increased with age, up to 7.01% among individuals aged 80 years and older, while the PM was the highest (3.80%) among individuals aged 5–14 years, which decreased with age. Between 1993 and 2019, the CMR, ASMR, and PM peaked in 2002, and the CMR then rebounded after the trough in this trend in 2011 while the ASMR continued to decrease, and the PM became relatively stable from 2011. Starting in 2005, the age-specific mortality rate for epilepsy had an increasing tendency over time among those aged 75 years or older, and a decreasing tendency in the younger age groups. @*Conclusions@#A declining tendency of mortality from epilepsy was found in the overall population of Korea over recent decades. However, epilepsy is a notable cause of death in children, and epilepsy-related mortality is increasing in the elderly population.
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Background@#and Purpose Epidemiological data on narcolepsy are rare in South Korea.We aimed to provide an overview of the burden of narcolepsy and its temporal trend in South Korea. @*Methods@#Patients with narcolepsy were identified by their registration in the Rare and Intractable Disease (RID) register and the Health Insurance Review and Assessment database.Individuals registered in the RID program with the code V234 were considered as having ‘definite narcolepsy’, while those who claimed health insurance with G47.4 as the primary diagnostic code were considered as having ‘probable narcolepsy’. We estimated the annual prevalence, incidence, and medical costs of narcolepsy between 2010 and 2019. @*Results@#The prevalence of definite narcolepsy was 8.4/100,000 in 2019, peaking at 32.0/100,000 in those aged 15–19 years. The prevalence was higher in males, with a relative risk of 1.72. The prevalence has increased over the past 6 years, with an average annual growth rate (AAGR) of 12.2%. The prevalence of probable narcolepsy was 10.7/100,000 in 2019. The incidence of definite narcolepsy increased up to 1.3/100,000 in 2019 with an AAGR of 7.1%. Annual medical expenditure for definite narcolepsy gradually increased up to 4.1 billion KRW in 2019, with a compound annual growth rate of 11.9%. @*Conclusions@#This study has provided the first nationwide estimates for narcolepsy in South Korea. The prevalence of diagnosed narcolepsy in South Korea was at the low end of the range of narcolepsy prevalence rates reported for other countries. However, the prevalence and incidence have been steadily increasing over the past decade.
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Background@#and Purpose We investigated the trends in the prescribing of antiseizure medication (ASM) over a 9-year period, and provide real-world data regarding ASM prescriptions of patients with epilepsy in South Korea. @*Methods@#This study used data in the Korean National Health Information Database for the period from 2009 to 2017. We included 18 oral ASMs, which were classified into older and newer ASMs based on them first becoming available on the market before or after 1991, respectively. The annual trends in ASM prescriptions were plotted over the 9-year study period, and changes in these trends were evaluated as average annual percentage changes (AAPCs) using Poisson regression. Age- and sex-stratified analyses were also conducted. @*Results@#Overall, the proportion of prescriptions involving polytherapy with three or more ASMs increased from 10.08% in 2009 to 10.99% in 2017 (AAPC=0.9%, p<0.001) over the 9-year study period. Among monotherapies, although valproate (VPA) was the most frequently prescribed ASM, the prescription rate of levetiracetam (LEV) steadily increased regardless of age and sex over the study period. The monotherapy prescription trends differed depending on age and sex. In the five most frequently used ASM combination regimens, the prescription rates of VPA/LEV, LEV/oxcarbazepine, and LEV/lamotrigine regimens showed increasing tendencies. In contrast, prescription rates for all combined regimens of older ASMs declined over time in all age groups. @*Conclusions@#This is the first epidemiological study of the changes in prescription trends for ASM in South Korea based on nationwide data from 2009 to 2017. We found progressive increases in the use of newer ASMs for both monotherapy and duotherapy, and for polytherapy with three or more ASMs over the 9-year study period.
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Background/Aims@#Frailty increases the risks of in-hospital adverse events such as delirium, falls, and functional decline in older adults. We assessed the feasibility and clinical relevance of frailty status in Korean older inpatients using the Clinical Frailty Scale (CFS) and Korean version of the Fatigue, Resistance, Ambulation, Illnesses, & Loss of Weight scale (K-FRAIL) questionnaires. @*Methods@#Frailty status was measured using the Korean-translated version of the CFS and K-FRAIL questionnaire within 3 days from admission in 144 consecutive patients aged 60 years or older. The correlation between CFS and K-FRAIL score was assessed. The criterion validity of CFS was assessed using receiver operating characteristic analysis. As outcomes, delirium, bedsore, length of stay (LOS), in-hospital mortality, and unplanned 30-day readmission were measured by reviewing medical records. @*Results@#The mean age of the study population was 70.1 years (range, 60 to 91), and 75 (52.1%) were men. By linear regression analysis, CFS and K-FRAIL were positively correlated (B = 0.72, p < 0.001). A CFS cutoff of ≥ 5 maximized sensitivity + specificity to classify frailty using K-FRAIL as a reference (C-index = 0.893). Higher frailty burden by both CFS and K-FRAIL was associated with higher LOS and bedsores. Unplanned readmission and in-hospital mortality were associated with higher CFS score but not with K-FRAIL score, after adjusting for age, gender, polypharmacy, and multimorbidity. @*Conclusions@#Frailty status by CFS was associated with LOS, bedsores, unplanned readmission, and in-hospital mortality. CFS can be used to screen high-risk patients who may benefit from geriatric interventions and discharge planning in acutely hospitalized older adults.
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Background@#and Purpose There have been few reports on recent trends in the occurrence of epilepsy. The aim of this study was to estimate the incidence and prevalence of epilepsy and analyze their annual trends in Korea over the period 2009–2017. @*Methods@#This nationwide population-based study was carried out using the National Health Insurance Service of Korea database. A prevalent case was defined as one of a patient receiving a prescription of anticonvulsants under the diagnostic codes for epilepsy or seizure. An incident case was ascertained by confirming the absence of any epilepsy-related diagnostic codes and anticonvulsant prescription for 2 years or more before the operational definition for a prevalent case was met. Alternative operational definitions for epilepsy were tested. The temporal trends of the incidence and prevalence of epilepsy were analyzed using a Poisson regression model, and are expressed as average annual percentage changes (AAPCs). @*Results@#The incidence of epilepsy increased from 28.7/100,000 persons in 2009 to 35.4/100,000 persons in 2017. The prevalence increased gradually from 3.4/1,000 persons in 2009 to 4.8/1,000 persons in 2017. These increasing trends were more evident among elderly subjects aged ≥75 years and in those who had codes for epilepsy or seizure as an additional diagnosis. Age standardization revealed a less prominent but still increasing trend in both incidence (AAPC=0.48%) and prevalence (AAPC=3.11%). @*Conclusions@#There have been increasing trends in both the prevalence and incidence of epilepsy in Korea between 2009 and 2017. This finding appears to be related to societal aging and the high incidence of symptomatic epilepsy in the elderly population.
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Background@#and Purpose To investigate the incidence and characteristics of neurological manifestations associated with coronavirus disease 2019 (COVID-19). @*Methods@#We reviewed the medical records of the consecutive patients with COVID-19 who were admitted to the central infectious diseases hospital designated for the treatment of COVID-19 in South Korea between March 2020 and September 2020. Newly developed neurological manifestations associated with COVID-19 were investigated. The frequency and clinical features of the neurological manifestations were analyzed according to disease severity, which was classified according to World Health Organization interim guidance. @*Results@#Of the 306 symptomatic patients, 186 (60.8%) developed at least one neurological manifestation during hospitalization. The most common neurological symptom was headache (n=102, 33.3%), followed by myalgia (n=96, 31.4%) and anosmia/ageusia (n=54, 17.6%). Acute stroke (all ischemic stroke) occurred in three (1.0%) patients, and new-onset seizures occurred in two (0.7%). Neurological manifestation was a presenting symptom of COVID-19 in 72 (23.5%) patients, and was the only symptom of COVID-19 in 12 (3.9%). Stroke, seizure, and impaired consciousness were significantly associated with severe to critical COVID-19, whereas headache and anosmia/ageusia were frequently found in patients with mild to moderate disease. @*Conclusions@#Neurological manifestations were commonly observed in patients with COVID-19. During the current pandemic, when patients present with new-onset neurological symptoms, COVID-19 may be considered as part of the differential diagnosis. Attention to severe neurological complications is needed, especially in patients with severe or critical COVID-19.
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Accurate identification of microbes facilitates the prediction, prevention, and treatment of human diseases. To increase the accuracy of microbiome data analysis, a long region of the 16S rRNA is commonly sequenced via paired-end sequencing. In paired-end sequencing, a sufficient length of overlapping region is required for effective joining of the reads, and high-quality sequencing reads are needed at the overlapping region. Trimming sequences at the reads distal to a point where sequencing quality drops below a specific threshold enhance the joining process. In this study, we examined the effect of trimming conditions on the number of reads that remained after quality control and chimera removal in the Illumina paired-end reads of the V3–V4 hypervariable region. We also examined the alpha diversity and taxa assigned by each trimming condition. Optimum quality trimming increased the number of good reads and assigned more number of operational taxonomy units. The pre-analysis trimming step has a great influence on further microbiome analysis, and optimized trimming conditions should be applied for Divisive Amplicon Denoising Algorithm 2 analysis in QIIME2 platform.
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Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.
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Background@#Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors. @*Conclusion@#CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.
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Background/Aims@#Frailty increases the risks of in-hospital adverse events such as delirium, falls, and functional decline in older adults. We assessed the feasibility and clinical relevance of frailty status in Korean older inpatients using the Clinical Frailty Scale (CFS) and Korean version of the Fatigue, Resistance, Ambulation, Illnesses, & Loss of Weight scale (K-FRAIL) questionnaires. @*Methods@#Frailty status was measured using the Korean-translated version of the CFS and K-FRAIL questionnaire within 3 days from admission in 144 consecutive patients aged 60 years or older. The correlation between CFS and K-FRAIL score was assessed. The criterion validity of CFS was assessed using receiver operating characteristic analysis. As outcomes, delirium, bedsore, length of stay (LOS), in-hospital mortality, and unplanned 30-day readmission were measured by reviewing medical records. @*Results@#The mean age of the study population was 70.1 years (range, 60 to 91), and 75 (52.1%) were men. By linear regression analysis, CFS and K-FRAIL were positively correlated (B = 0.72, p < 0.001). A CFS cutoff of ≥ 5 maximized sensitivity + specificity to classify frailty using K-FRAIL as a reference (C-index = 0.893). Higher frailty burden by both CFS and K-FRAIL was associated with higher LOS and bedsores. Unplanned readmission and in-hospital mortality were associated with higher CFS score but not with K-FRAIL score, after adjusting for age, gender, polypharmacy, and multimorbidity. @*Conclusions@#Frailty status by CFS was associated with LOS, bedsores, unplanned readmission, and in-hospital mortality. CFS can be used to screen high-risk patients who may benefit from geriatric interventions and discharge planning in acutely hospitalized older adults.
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Background@#and Purpose There have been few reports on recent trends in the occurrence of epilepsy. The aim of this study was to estimate the incidence and prevalence of epilepsy and analyze their annual trends in Korea over the period 2009–2017. @*Methods@#This nationwide population-based study was carried out using the National Health Insurance Service of Korea database. A prevalent case was defined as one of a patient receiving a prescription of anticonvulsants under the diagnostic codes for epilepsy or seizure. An incident case was ascertained by confirming the absence of any epilepsy-related diagnostic codes and anticonvulsant prescription for 2 years or more before the operational definition for a prevalent case was met. Alternative operational definitions for epilepsy were tested. The temporal trends of the incidence and prevalence of epilepsy were analyzed using a Poisson regression model, and are expressed as average annual percentage changes (AAPCs). @*Results@#The incidence of epilepsy increased from 28.7/100,000 persons in 2009 to 35.4/100,000 persons in 2017. The prevalence increased gradually from 3.4/1,000 persons in 2009 to 4.8/1,000 persons in 2017. These increasing trends were more evident among elderly subjects aged ≥75 years and in those who had codes for epilepsy or seizure as an additional diagnosis. Age standardization revealed a less prominent but still increasing trend in both incidence (AAPC=0.48%) and prevalence (AAPC=3.11%). @*Conclusions@#There have been increasing trends in both the prevalence and incidence of epilepsy in Korea between 2009 and 2017. This finding appears to be related to societal aging and the high incidence of symptomatic epilepsy in the elderly population.
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Background@#and Purpose To investigate the incidence and characteristics of neurological manifestations associated with coronavirus disease 2019 (COVID-19). @*Methods@#We reviewed the medical records of the consecutive patients with COVID-19 who were admitted to the central infectious diseases hospital designated for the treatment of COVID-19 in South Korea between March 2020 and September 2020. Newly developed neurological manifestations associated with COVID-19 were investigated. The frequency and clinical features of the neurological manifestations were analyzed according to disease severity, which was classified according to World Health Organization interim guidance. @*Results@#Of the 306 symptomatic patients, 186 (60.8%) developed at least one neurological manifestation during hospitalization. The most common neurological symptom was headache (n=102, 33.3%), followed by myalgia (n=96, 31.4%) and anosmia/ageusia (n=54, 17.6%). Acute stroke (all ischemic stroke) occurred in three (1.0%) patients, and new-onset seizures occurred in two (0.7%). Neurological manifestation was a presenting symptom of COVID-19 in 72 (23.5%) patients, and was the only symptom of COVID-19 in 12 (3.9%). Stroke, seizure, and impaired consciousness were significantly associated with severe to critical COVID-19, whereas headache and anosmia/ageusia were frequently found in patients with mild to moderate disease. @*Conclusions@#Neurological manifestations were commonly observed in patients with COVID-19. During the current pandemic, when patients present with new-onset neurological symptoms, COVID-19 may be considered as part of the differential diagnosis. Attention to severe neurological complications is needed, especially in patients with severe or critical COVID-19.
ABSTRACT
Accurate identification of microbes facilitates the prediction, prevention, and treatment of human diseases. To increase the accuracy of microbiome data analysis, a long region of the 16S rRNA is commonly sequenced via paired-end sequencing. In paired-end sequencing, a sufficient length of overlapping region is required for effective joining of the reads, and high-quality sequencing reads are needed at the overlapping region. Trimming sequences at the reads distal to a point where sequencing quality drops below a specific threshold enhance the joining process. In this study, we examined the effect of trimming conditions on the number of reads that remained after quality control and chimera removal in the Illumina paired-end reads of the V3–V4 hypervariable region. We also examined the alpha diversity and taxa assigned by each trimming condition. Optimum quality trimming increased the number of good reads and assigned more number of operational taxonomy units. The pre-analysis trimming step has a great influence on further microbiome analysis, and optimized trimming conditions should be applied for Divisive Amplicon Denoising Algorithm 2 analysis in QIIME2 platform.
ABSTRACT
Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.
ABSTRACT
Background@#Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors. @*Conclusion@#CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.
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In the oral cavity, complex microbial community is shaped by various host and environmental factors. Extensive literature describing the oral microbiome in the context of oral health and disease is available. Advances in DNA sequencing technologies and data analysis have drastically improved the analysis of the oral microbiome. For microbiome study, bacterial 16S ribosomal RNA gene amplification and sequencing is often employed owing to the cost-effective and fast nature of the method. In this review, practical considerations for performing a microbiome study, including experimental design, molecular analysis technology, and general data analysis, will be discussed.
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Background@#Status epilepticus is a severe neurologic emergency comprising significant morbidity and mortality. This study investigated the epidemiologic features of status epilepticus in Korea from 2010 to 2019. @*Methods@#We used the Healthcare Bigdata Hub of the Korea National Health Insurance Database to identify records with principal diagnostic codes for status epilepticus (G41) using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems from January 2010 to December 2019. This database only included patients with health insurance and not those with medical aid. The annual number of patients, costs, and regional differences were evaluated. The patients hospitalized under the principal diagnostic code for status epilepticus were considered as incident cases. @*Results@#The total number of patients with a diagnosis of status epilepticus increased annually from 3,110 in 2010 to 5,840 in 2019 at a compound annual growth rate of 7.3%. The incidence of status epilepticus per 100,000 population increased steadily from 2.21 in 2010 to 5.33 in 2019. Health care expenditures showed continued growth at a faster rate of 18.4%. When categorized by age groups, the growth rate was markedly higher in age groups >60 years. @*Conclusions@#In Korea, the incidence and cost of status epilepticus have increased from 2010 to 2019. Considering a possible underestimation of the incidence owing to data characteristics, the real incidence of status epilepticus may be higher. This trend in the incidence of status epilepticus can be mostly attributed to the increase of status epilepticus in the older population.
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Epilepsy is associated with an increased risk of premature death. Epilepsy-related premature mortality imposes a significant burden on public health. This review aims to update the previous assessments of mortality among people with epilepsy and to identify associated factors, causes of death, and preventable causes of death in epilepsy patients. We also reviewed the mortality of epilepsy patients who had undergone epilepsy surgery. Finally, we suggest a further direction of studies about the mortality of people with epilepsy.
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Background@#This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs). @*Methods@#In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed. @*Results@#Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators’ assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients’ LDL-C levels was the primary reason for non-intensification of statin therapy. @*Conclusion@#Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.
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X-linked adrenoleukodystrophy (X-ALD) occurs due to mutations in the ABCD1 gene that encodes the peroxisomal membrane protein peroxisomal transporter ATP-binding cassette sub-family D member 1 (ABCD1). Degradation of very long-chain fatty acids in peroxisomes is impaired owing to ABCD dysfunction, subsequently leading to adrenomyeloneuropathy, cerebral adrenoleukodystrophy, and adrenal insufficiency. X-ALD frequently induces idiopathic Addison's disease in young male patients. Here, we confirmed the diagnosis of X-ALD in a young male patient with primary adrenal insufficiency, and identified a novel ABCD1 gene mutation (p.Trp664*, c.1991 G>A).