OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

OBJECTIVE: To explore the genetic basis for a neonate affected with Glutaric aciduria type I (GA-I). METHODS: Targeted capture and high-throughput sequencing was carried out for the proband and her parents. Candidate variants were verified by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous variants of the GCDH gene, namely c.523G>A and c.1190T>C, which was derived from her father and mother, respectively. CONCLUSION The compound heterozygous variants of the GCDH gene probably underlay the GA-I in the patient.
Amino Acid Metabolism, Inborn Errors/genetics* ; Brain Diseases, Metabolic/genetics* ; Child ; Female ; Glutaryl-CoA Dehydrogenase/genetics* ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Mutation

OBJECTIVE: To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1). METHODS: High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing. RESULTS: High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant. CONCLUSION The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.
Brain Diseases, Metabolic, Inborn/genetics* ; Creatine ; Genetic Testing ; Heterozygote ; Humans ; Mental Retardation, X-Linked ; Mutation

OBJECTIVE: To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ. METHODS: GCDH gene variants was detected by Sanger sequencing among the three children and their family members. RESULTS: Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c.532G>A (p.Gly178Arg) and c.655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c.532G>A(p.Gly178Arg) and c.655G>A (p.Ala219Thr) variants. Patient 2 carried c.532G>A (p.Gly178Arg) and a novel c.1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c.532G>A (p.Gly178Arg) and c.1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c.532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers. CONCLUSION The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.
Amino Acid Metabolism, Inborn Errors ; genetics ; Brain Diseases, Metabolic ; genetics ; Female ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; Heterozygote ; Humans ; Male

Although the number of prescriptions and dependence on sleeping pills are increasing, the associations with unexpected abnormal behaviors and metabolic diseases caused by the overuse of sleeping pills are not well understood. In particular, such as abnormal eating-behavior and the occurrence of metabolic disorders caused by psychological unstable states are reported. For this reason, herbal medicine, which has not had such side effects in recent years, is attracting attention as an alternative medicine/food for sleeping inducer. We have used ethanol extracts from Passiflora incarnata (PI) to steadily obtain positive effects on sleep and brain microenvironment. However, as mentioned earlier, sleep-inducing efficacy can only be used safely if the behavioral and metabolic abnormalities do not appear.Thus, in this study, we used Phenomaster equipment to continuously monitor the movement, feeding, water consumption, gas changes, etc. in C57BL/6 mice at a dose of 500 mg/kg/day for 5 consecutive days with PI extract group compared with the control group. Before sacrifice, differences in body composition of mice were also compared. Monitoring of 24 h/5 days through the equipment showed no change in PI-treated group in anything except for significant decrease in blood melatonin levels and activity after PI administration. Taken together, the statistically insignificance of any behavioral and metabolic phenomenon produced by repeated treatment of PI are not only expected to have an accurate sleep effect, but are also free of side effects of the prescribed sleeping pills. This study has given us greater confidence in the safety of the PI extracts we use for sleep-inducer.
Administration, Oral ; Animals ; Body Composition ; Brain ; Drinking ; Ethanol ; Herbal Medicine ; Melatonin ; Metabolic Diseases ; Metabolic Phenomena ; Mice ; Passiflora ; Prescriptions ; Sleep Initiation and Maintenance Disorders

OBJECTIVE: To review the clinical features of a male twin affected with glutaric academia type I (GA-I) and analyze the variations of glutaryl-CoA dehydrogenase (GCDH) gene. METHODS: Clinical data of the pair of twins and their parents were collected. Genomic DNA was extracted from peripheral blood samples, and variants of GCDH genes were detected by capture sequencing using a customized panel. Variants of the twins and their parents were verified by Sanger sequencing. RESULTS: The level of glutaric acyl carnitine (C5DC + C6OH) was 3.26 μmol/L in the male twin. The relative level of glutaric acid in urine was 547.51 by gas chromatography mass spectrometry analysis. Cerebral ultrasonography showed that the patient had subependymal hemorrhage, but no serious clinical manifestation was noted. After treating with special formula milk powder and L-carnitine, the boy showed good growth and development. Two heterozygous variants of the GCDH gene were detected in the patient, among which c.416C>G was suspected to be pathogenic, while c.109_110delCA was unreported. The variants were respectively inherited from his parents. The twin girl only carried the c.416C>G variant. CONCLUSION GA-I can be diagnosed by mass spectrometry, urine gas chromatographic mass spectrometry, imaging as well as genetic diagnosis. Early diagnosis and intervention is important.
Amino Acid Metabolism, Inborn Errors ; genetics ; Brain Diseases, Metabolic ; genetics ; Female ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; Humans ; Male ; Mutation ; Phenotype

BACKGROUND: Organic solvent-induced chronic toxic encephalopathy (CTE) is known as a non-progressive disorder that does not progress after diagnosis. The authors present a case those symptoms worsened after continued exposure to organic solvent after returning to work. Because such a case has not been reported in South Korea to the best of our knowledge, we intend to report this case along with literature review. CASE PRESENTATION: A 59-year-old man, who performed painting job at a large shipyard for 20 years, was receiving hospital treatment mainly for depression. During the inpatient treatment, severe cognitive impairment was identified, and he visited the occupational and environmental medicine outpatient clinic for assessing work relatedness. In 1984, at the age of 27, he began performing touch-up and spray painting as a shipyard painter. Before that he had not been exposure to any neurotoxic substances. In 2001, at the age of 44, after 15 years of exposure to mixed solvents including toluene, xylene and others, he was diagnosed with CTE International Solvent Workshop (ISW) type 2A. After 7 years of sick leave, he returned to work in 2006. And he repeated return-to-work and sick leave in the same job due to worsening of depressive symptoms. He had worked four times (2006–2010, 2011–2011, 2011–2011, 2016–2017) for a total of 5 years as a shipyard painter after first compensation. During the return-to-work period, the mean values of the mixed solvent index ranged from 0.57 to 2.15, and except for a one semiannual period, all mean values were above the standard value of 1. We excluded other diseases that can cause cognitive impairment like central nervous system diseases, brain injury, psychological diseases and metabolic diseases with physical examinations, laboratory tests, and brain image analysis. And finally, throughout neuropsychological tests, an overall deterioration in cognitive function was identified compared to 2002, and the deterioration types was similar to that often shown in the case of CTE; thus a diagnosis of CTE (ISW) type 3 was made. CONCLUSION: This case is showing that CTE can go on with continued exposure to mixed solvents. Appropriate “fitness to work” should be taken to prevent disease deterioration especially for the sick leave workers.
Ambulatory Care Facilities ; Brain ; Brain Injuries ; Central Nervous System Diseases ; Cognition ; Cognition Disorders ; Compensation and Redress ; Depression ; Diagnosis ; Education ; Environmental Medicine ; Humans ; Inpatients ; Korea ; Metabolic Diseases ; Middle Aged ; Neuropsychological Tests ; Neurotoxicity Syndromes ; Occupational Diseases ; Paint ; Paintings ; Physical Examination ; Return to Work ; Sick Leave ; Solvents ; Toluene ; Xylenes

Taurine is an abundant, β-amino acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.
Acidosis, Lactic ; Arthritis ; Brain Diseases ; Calcium ; Cardiovascular System ; Central Nervous System ; Cytoprotection ; Energy Metabolism ; Gene Expression ; Heart Failure ; Japan ; MELAS Syndrome ; Metabolic Diseases ; Mitochondrial Diseases ; Neurodegenerative Diseases ; Pathology ; Quality Control ; Taurine*

PURPOSE: The aim of this study was to evaluate the clinical characteristics of children diagnosed as cryopyrin-associated periodic syndrome (CAPS) in Korea. METHODS: Diagnosis was made based on clinical features and confirmed by a mutation in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene. Especially, osteocartilaginous overgrowth in the patella or distal femur was so characteristic that its presence warranted a diagnosis of chronic infantile neurologic cutaneous and articular/NOMID. RESULTS: We observed the clinical features of 9 Korean CAPS patients. All the patients suffered from an urticarial rash with recurrent fever. Among the 9 patients, 6 presented with rash and 4 with fever on the 1st or 2nd days of birth. Eight patients showed myalgia, and 7 patients showed arthralgia in the joints, and 6 patients showed radiologic findings of arthropathy including cupping of the metaphysis, excessive growth of the epiphysis, osteopenia or overgrowth of the cartilage. Four patients showed brain atrophy, enlarged ventricles or leptomeningeal enhancement on magnetic resonance imaging. Intellectual disability was observed in 1 patient. Five patients had eye involvement as conjunctivitis, uveitis, chorioretinitis, avascular area or papillary edema, and 3 patients showed progressive hearing loss. All 9 patients showed increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). CONCLUSIONS: All the patients carried a mutation on exon 3 of the CIAS1 gene. After the anakinra (interleukin-1 receptor antagonist) therapy, the fever and rash immediately disappeared, and CRP and ESR were improved.
Arthralgia ; Atrophy ; Blood Sedimentation ; Bone Diseases, Metabolic ; Brain ; C-Reactive Protein ; Cartilage ; Child ; Chorioretinitis ; Conjunctivitis ; Cryopyrin-Associated Periodic Syndromes ; Diagnosis ; Edema ; Epiphyses ; Exanthema ; Exons ; Femur ; Fever ; Hearing Loss ; Humans ; Intellectual Disability ; Interleukin 1 Receptor Antagonist Protein ; Joints ; Korea ; Magnetic Resonance Imaging ; Myalgia ; Parturition ; Patella ; Uveitis

Blood glucose homeostasis is well maintained by coordinated control of various hormones including insulin and glucagon as well as cytokines under normal conditions. However, chronic exposure to diabetic environment with high fat/high sugar diets and physical/mental stress can cause hyperglycemia, one of main characteristics of insulin resistance, metabolic syndrome, and diabetes. Hyperglycemia impairs organogenesis and induces organ abnormalities such as cardiac defect in utero. It is a risk factor for the development of metabolic diseases in adults. Resulting glucotoxicity affects peripheral tissues and vessels, causing pathological complications including diabetic neuropathy, nephropathy, vessel damage, and cardiovascular diseases. Moreover, chronic exposure to hyperglycemia can deteriorate cognitive function and other aspects of mental health. Recent reports have demonstrated that hyperglycemia is closely related to the development of cognitive impairment and dementia, suggesting that there may be a cause-effect relationship between hyperglycemia and dementia. With increasing interests in aging-related diseases and mental health, diabetes-related cognitive impairment is attracting great attention. It has been speculated that glucotoxicity can result in structural damage and functional impairment of brain cells and nerves, hemorrhage of cerebral blood vessel, and increased accumulation of amyloid beta. These are potential mechanisms underlying diabetes-related dementia. Nutrients and natural food components have been investigated as preventive and/or intervention strategy. Among candidate components, resveratrol, curcumin, and their analogues might be beneficial for the prevention of diabetes-related cognitive impairment. The purposes of this review are to discuss recent experimental evidence regarding diabetes and cognitive impairment and to suggest potential nutritional intervention strategies for the prevention and/or treatment of diabetes-related dementia.
Adult ; Alzheimer Disease* ; Amyloid ; Blood Glucose ; Blood Vessels ; Brain ; Cardiovascular Diseases ; Cognition ; Cognition Disorders ; Curcumin ; Cytokines ; Dementia ; Diabetes Mellitus ; Diabetic Neuropathies ; Diet ; Glucagon ; Hemorrhage ; Homeostasis ; Humans ; Hyperglycemia ; Insulin ; Insulin Resistance ; Mental Health ; Metabolic Diseases ; Organogenesis ; Risk Factors