• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.21-30
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• 2023

Inherited metabolic disorders (IMD) are a group of disorders caused by defects in specific biochemical pathways. Up to 85% of IMD display predominantly neurological manifestations by affecting neurodevelopment or causing neurodegeneration. These neurometabolic disorders present with a variety of neurological and non-neurological manifestations. Early diagnosis of IMD is important because some disorders can be treated or improved with specific treatment if detected early. For prompt diagnosis and treatment, it is important to suspect IMD by being familiar with the clinical characteristics, biochemical abnormalities, and characteristic neuroimaging patterns that appear in IMD. Genetic testing, including next-generation sequencing, is also important in diagnosing IMD. During the follow-up of patients with IMD, it is necessary to conduct regular physical and neurological examinations in addition to disease-specific management.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.34-38
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• 2020

The term dopa-responsive dystonia (DRD) is used to describe a group of neurometabolic disorders, which are characterized by dystonia, and are typically associated with diurnal fluctuations and respond to levodopa treatment. Autosomal dominant DRD (DYT5a, MIM# 128230) is caused by a heterozygous mutation in the GTP cyclohydrolase 1 (GCH1) gene (MIM# 600225). GCH1 encodes an enzyme, which is involved in the biosynthesis of tetrahydrobiopterin, an essential co-factor for tyrosine hydroxylase. Herein, we report the case of a 16-year-old girl who was diagnosed with DYT5a. She exhibited additional unusual clinical features, including intellectual disability, depression, multiple skeletal anomalies, and short stature, which are not commonly observed in patients with DYT5a. The patient harbored a heterozygous missense variant, c.539A>C, p.Gln180Pro, in the GCH1 gene, which was identified by targeted gene panel analysis using next-generation sequencing.

• Journal of mucopolysaccharidosis and rare diseases
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• v.5 no.1
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• pp.8-11
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• 2021

Glutaric aciduria type 1 (GA1; OMIM #231670) is a rare autosomal recessive-inherited neurometabolic disorder caused by the deficiency of glutaryl-CoA dehydrogenase (GCDH), which is encoded by the GCDH gene. It results in the accumulation of glutaric acid (GA), 3-hydroxyglutaric acid (3-OH-GA), glutaconic acid, and glutarylcarnitine (C5DC). These metabolites are considered to damage the striatum through an excitotoxic mechanism. The treatments of GA1 known to date are metabolic maintenance treatment based on a low-lysine diet and emergency treatment during acute illness. However, treatment after the onset of neurological symptoms has limited effectiveness and is associated with poor outcomes, and the effect of treatment and disease course after treatment are not good. After the implementation of newborn screening, the incidence of acute encephalopathic crisis fell to 10%-20% with early diagnosis, preventative dietary management, and aggressive medical intervention during acute episodes. Recently, several cohort studies have been published on the natural course and treatment of GA1 patients. This mini review will cover the clinical symptoms, natural history, and treatment of GA1 through a literature review.

• Journal of the Korean Magnetic Resonance Society
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• v.7 no.1
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• pp.1-15
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• 2003

PURPOSE - To investigate neurometabolism from the brain destructive lesions and striatal putamen-pallidus regions to the clinically worst side in patients with Parkinson's disease after stereotactic functional neurosurgery. METHODS - Using proton magnetic resonance spectroscopy ($^1$H MRS), fifteen patients (7 males and 8 females; mean age 56.5 years; age range 43-67 years) with Parkinson's disease (PD) were studied to measure N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho) and lactate (Lac) levels on the neurosurgical lesions of thalamus, globus pallidus and striatal putamen-pallidus regions in a brain. RESULTS - Brain destructive lesion and striatal putamen-pallidus region in PD compared with controls were highly and significantly related to NAA/Cho ratios reduction, respectively (P =0.002, P =0.04), but showed no difference from the same regions of PD prior to neurosergery (P =0.06, P =0.77). Increased lactate peaks at 1.3 ppm were present in all the cerebral lesions, and these resonances were confirmed at a long TE =136 ms, indicating that these signals distinguished from lipids. CONCLUSIONS - Our results suggest that NAA/Cho ratios may provide as a neurometabolite marker for neurochemical changes in brain surgical lesion, and the ratios might be related to functional change of neuropathophysiological status in the striatal putamen-pallidus region of PD. Increase of lactate signals, being remarkable in surgical lesions, could be consistent with a common consequence of surgical necrosis. Therefore, MR spectroscopy could be a sensitive diagnostic tool in monitoring neurometabolic changes in PD with neurosurgical treatment.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.1
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• pp.9-14
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• 2022

Glutaric aciduria type 1 (GA1; OMIM #231670) is a rare autosomal recessive inherited neurometabolic disorder caused by the deficiency of glutaryl-CoA dehydrogenase. Infantile-onset GA1 is the most common form characterized by striatal injury and progressive movement disorder, and it is often triggered by an acute encephalopathic crisis within the first three years of life. Once this crisis occurs, there is a high likelihood for ineffective or limited conventional interventions, neurological disorders, or even death. Therefore, early diagnosis and immediate preventive management, such as dietary therapy, is essential. In the past decades, newborn screening (NBS) by tandem mass spectrometry for GA1 has been largely introduced in many countries including Korea, and it has led to improvements in the neurological outcomes of patients with GA1. In this review, the clinical symptoms, natural histories, and outcomes before and after the introduction of NBS in patients are discussed.

• Journal of the Korean Child Neurology Society
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• v.25 no.3
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• pp.204-207
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• 2017

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH syndrome) is a neurometabolic disorder with highly variable clinical severity ranging from mild learning disability to severe encephalopathy. Diagnosis of HHH syndrome can easily be delayed or misdiagnosed due to insidious symptoms and incomplete biochemical findings, in that case, genetic testing should be considered to confirm the diagnosis. HHH syndrome is caused by biallelic mutations of SLC25A15, which is involved in the urea cycle and the ornithine transport into mitochondria. Here we report a boy with spastic paraplegia and asymptomatic younger sister who have compound heterozygous mutations of c.535C>T (p.R179^*) and c.116C>A (p.T39K) in the SLC25A15 gene. We identified that p.T39K mutation is a novel pathogenic mutation causing HHH syndrome and that p.R179^*, which is prevalent in Japanese and Middle Eastern heritage, is also found in the Korean population.