• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.25-28
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• 2015

Mitochondrial disorders are rare metabolic diseases. They often present during neonatal period but with nonspecific clinical features such as feeding difficulties, failure to thrive, and seizures. Mitochondrial defects have also known to be associated with neurological disorders, as well as cancers. We report the first case of neonatal mitochondrial respiratory chain defect with sarcoma botryoides confirmed by pathologic diagnosis, suggesting another possible link between mitochondrial dysfunction and cancer.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.3
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• pp.95-98
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• 2018

A striking feature of mitochondrial disorders is the vast heterogeneity in their clinical symptoms that ranges from a single organ to severe multisystem involvement. Though a variety of ocular symptoms such as ptosis, pigmentary retinal degeneration, external ophthalmoplegia, and optic nerve atrophy can occur in association with mitochondrial cytopathies, progressive bilateral cataracts are rare among their ocular findings. A 5-year-old girl with no previous medical history came to our hospital presenting symptoms of seizure. She started showing progressive developmental regression, increased seizure frequency, hypotonia, general weakness, dysphagia and decreased vision. Lactic acidosis was noted in metabolic screening test and we confirmed mitochondrial respiratory chain complex I defect in spectrophotometric enzyme assay using the muscle tissue. Progressive bilateral cataracts then developed and were fully evident at the age of 7. She underwent cataract extraction with posterior chamber lens implantation. We are reporting a case of mitochondrial respiratory chain defect with multiorgan involvements including bilateral progressive cataract, an uncommon ocular manifestation. Ophthalmologic evaluation is highly recommended not to overlook the possible ocular manifestations in mitochondrial disorders.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.2
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• pp.72-77
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• 2015

Purpose: Deficits of the respiratory chain are reported to be the major cause of Leigh syndrome is said to be the underlying causes. The need for biochemical diagnosis to draw more accurate diagnosis or prognosis to support treatments is rapidly increasing. This study tried to analyze the aspects of clinical characteristics and biochemical diagnosis of mitochondrial respiratory chain complex (MRC) defect in Leigh syndrome, using methods of biochemical enzyme assay. Methods: We included total number of 47 patients who satisfied the clinical criteria of Leigh syndrome and confirmed by biochemical diagnosis. All those patients went through muscle biopsy to perform biochemical enzyme assay to analyze MRC enzyme in order to find the underlying cause of Leigh syndrome. Results: MRC I defect was seen in 23 (48.9%) cases taking the first place and MRC IV defect in 15 (31.9%) following it. There were 9 (19.2%) cases of combined MRC defect. Combined cases of type I and IV were detected in 7 (14.9%) patients while type I and V in 2 (4.3%). The onset age of symptom was less than 1 year old in 28 (59.6%). The most common early symptom, observed in 23 (48.9%), was delayed development, but there were other various neurological symptoms observed as well. In regard with the disease progression, 35 (74.5%) patients showed slowly progressive course, the one that progressed continuously but slowly over 2 years of period. As for Maximum motor development, 22 (46.8%) were bed-ridden state, most of them suffering serious delayed development. Patients showed various symptoms with different organs involved, though neuromuscular involvement was most prominent. Delayed development was seen in all cases. Multifocal lesion in brain MRI study was seen in 36 (76.6 %) cases, taking a greater percentage than 11 (23.4%) cases with single lesion. In MR spectroscopy study, the characteristic lactate peak of mitochondrial disease was identified in 20 (42.6%) patients. Conclusions: Further analysis of clinical and biochemical diagnosis on more extended group of patients with Leigh syndrome will enable us to improve diagnostic precision and to understand the natural course of mitochondrial disease.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.1 no.1
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• pp.15-17
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• 2001

• Clinical and Experimental Pediatrics
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• v.53 no.12
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• pp.994-999
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• 2010

Purpose: Mitochondrial dysfunction can present with various symptoms depending on the organ it has affected. This research tried to analyze the ophthalmologic symptoms and ophthalmologic examination (OE) results in patients with mitochondrial disease (MD). Methods: Seventy-four patients diagnosed with mitochondrial respiratory chain complex defect with biochemical enzyme assay were included in the study. They were divided into 2 groups based on the OE results by funduscopy and were analyzed on the basis of their clinical features, biochemical test results, morphological analysis, and neuroimaging findings. Results: Thirty-seven (50%) of the 74 MD patients developed ophthalmologic symptoms. Abnormal findings were observed in 36 (48.6%) patients during an OE, and 16 (21.6%) of them had no ocular symptoms. Significantly higher rates of prematurity, clinical history of epilepsy or frequent apnea events, abnormal light microscopic findings in muscle pathology, diffuse cerebral atrophy in magnetic resonance imaging, and brainstem hyperintensity and lactate peaks in magnetic resonance spectroscopy were noted in the group with abnormal OE results. Conclusion: Although the ophthalmologic symptoms are not very remarkable in MD patients, an OE is required. When the risk factors mentioned above are observed, a more active approach should be taken in the OE because a higher frequency of ocular involvement can be expected.

• Clinical and Experimental Pediatrics
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• v.52 no.4
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• pp.471-475
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• 2009

Purpose : Mitochondrial disorders are a clinical entity characterized by diverse symptoms and signs of involvement of various systems. Furthermore, the disorders are known to show ophthalmologic manifestations as well as neurological findings. Visually evoked potential is a sensitive measure to check the integrity of the visual pathway. In this study, we have investigated the value of visually evoked potential in mitochondrial disorders with respiratory chain defects. Methods : Nineteen patients diagnosed with mitochondrial respiratory chain complex I defect as confirmed by spectrophotometric enzyme assay in muscle samples were enrolled for this study. The patients underwent a visually evoked potential study. We classified the results into four groups and compared these with clinical ophthalmologic findings. Results : Among the 19 patients, 14 showed abnormal visually evoked potential findings. Seven patients showed abnormal clinical ophthalmologic findings. All patients with abnormal ophthalmologic findings showed abnormal visually evoked potential findings. Among the 12 patients with normal ophthalmologic findings, seven showed abnormal results in visually evoked potential. Conclusion : Visually evoked potential study could be used as an effective screening tool for mitochondrial disorders to detect ophthalmologic and neurological abnormalities.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.191-194
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• 2014

Mitochondrial myopathy results from a primary dysfunction of the respiratory chain and is frequently accompanied with endocrine manifestations. Among the endocrine manifestations of mitochondrial disease, diabetes mellitus is relatively common. Diabetes mellitus in the mitochondrial myopathy is usually insulin dependent due to the defect in insulin secretion resulted from mitochondrial dysfunction. But it is seldom manifested as diabetes ketoacidosis and doesn't usually have an auto-antibody. We report a patient with mitochondrial myopathy who was diagnosed as having diabetes mellitus by presenting as diabetes ketoacidosis and had both of the auto-glutamic acid decarboxylase (GAD) antibody and anti-insulin auto-antibody.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.199-204
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• 2009

Purpose : Seizure associated with fever may indicate the presence of underlying inherited metabolic diseases. The present study was performed to investigate the presence of underlying metabolic diseases in patients with complex febrile seizures, using analyses of urine organic acids. Method : We retrospectively analyzed and compared the results of urine organic acid analysis with routine laboratory findings in 278 patients referred for complex febrile seizure. Results : Of 278 patients, 132 had no abnormal laboratory findings, and 146 patients had at least one of the following abnormal laboratory findings: acidosis (n=58), hyperammonemia (n=55), hypoglycemia (n=21), ketosis (n=12). Twenty-six (19.7 %) of the 132 patients with no abnormal findings and 104 (71.2%) of the 146 patients with statistically significant abnormalities showed abnormalities on the organic acid analysis (P<0.05). Mitochondrial respiratory chain disorders (n=23) were the most common diseases found in the normal routine laboratory group, followed by PDH deficiency (n=2) and ketolytic defect (n=1). In the abnormal routine laboratory group, mitochondrial respiratory chain disorder (n=29) was the most common disease, followed by ketolytic defects (n=27), PDH deficiency (n=9), glutaric aciduria type II (n=9), 3-methylglutaconic aciduria type III (n=6), biotinidase deficiency (n=5), propionic acidemia (n=4), methylmalonic acidemia (n=2), 3-hydroxyisobutyric aciduria (n=2), orotic aciduria (n=2), fatty acid oxidation disorders (n=2), 2-methylbranched chain acyl CoA dehydrogenase deficiency (n=2), 3-methylglutaconic aciduria type I (n=1), maple syrup urine disease (n=1), isovaleric acidemia (n=1), HMG-CoA lyase deficiency (n=1), L-2-hydroxyglutaric aciduria (n=1), and pyruvate carboxylase deficiency (n=1). Conclusion : These findings suggest that urine organic acid analysis should be performed in all patients with complex febrile seizure and other risk factors for early detection of inherited metabolic diseases.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.155-165
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• 2000

Background: The phagolysosomal function of alveolar macrophage against M. tuberculosis infection is influenced by Nramp1, which is encoded by the NRAMP1 gene. There are several genetic polymorphisms in NRAMP1, and these polymorphisms affect the innate host resistance through the defect in production and function of Nramp1. To investigate this relationship, the NRAMP1 genetic polymorphism in patients with primary tuberculous pleurisy was determined. Methods: Fifty-six primary tuberculous pleurisy patient, who were diagnosed by pleural biopsy, were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. Three genetic polymorphisms of NRAMP1, such as a single point mutation in intron 4(469+14G/C, INT4), a nonconservative single-base substitution at codon 543 that changes aspartic acid to asparagine(D543N) and a TGTG deletion in the 3' untranslated region(1729+55delI4, 3'UTR), were determined. Polymerase chain reaction(PCR) and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) were used. Results: The frequencies of mutant genotypes of INT4 and 3'UTR were significantly high in pleurisy group(p=0.001, p=0.023). But the frequencies of D543N were not significantly different between the two groups(p=0.079). The odds ratios, which are a comparison with wild genotype for determining mutant genotypes, were 8. 022(95% confidence interval=2.422-26.572) for INT4 and 5.733(95% confidence interval = 1.137~28.916) for 3'UTR ; these were statistically significant But the ratio for D543N was not significant In the combined analysis of the INT4 and 3'UTR polymorphisms, the odds ratios were 6.000(95% confidence interval = 1.461~24.640) for GC/++ genotype and 14.000(95% confidence interval=1.610~121.754) for GC/+del when compared with GG/++ homozygotes ; these were statistically significant. Conclusion: Among the NRAMP1 genetic polymorphisms, a single point mutation in intron 4(469+14G/C, INT4) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR) were closely related to the primary tuberculous pleurisy.

• Neonatal Medicine
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• v.17 no.2
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• pp.254-261
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• 2010

Little is known about neonatal mitochondrial disease, though mitochondrial metabolic disorders may often present in the neonatal period because of the high energy requirement of neonate. In newborn period, common presentations are not specific and the disease course may be rapid and fatal. In this study, we report three cases of neonatal mitochondrial disease. The first case was strongly suspected because of sudden seizure and mental change with severe lactic acidosis, and multiorgan failure. Plasma lactate/pyruvate (L/P) ratio was increased to 55.6 with marked lactic aciduria and increased plasma alanin up to 2,237 nmol/mL. In the second patient, a peritoneal dialysis was performed for acute adrenal and renal failure, but metabolic acidosis persisted. Plasma L/P ratio was increased to 23.9, and MRC I (mitochondrial respiratory chain defect) was diagnosed through the enzymatic analysis of the muscles. The third case showed repetitive episode of lactic acidosis during the first two months of life, hypotonia, failure to thrive and feeding difficulties. We found markedly increased cerebrospinal fluid L/P ratio up to 57 though plasma L/P ratio(19.4) was borderline with increased plasma lactate. The lactate peak was prominent in brain magnetic resonance spectroscopy (MRS). MRC II was confirmed through muscle biopsy. Plasma lactate level and lactate peak of brain MRS were normalized after conservative treatment.