• Journal of Genetic Medicine
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• v.16 no.2
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• pp.55-61
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• 2019

Purpose: Genetic defects in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases were first identified as causes of various disorders in 2007. Variants in IARS2, which encodes a mitochondrial isoleucyl-tRNA synthetase, were first reported in 2014. These variants are associated with diverse phenotypes ranging from CAGSSS (CAtaracts, Growth hormone deficiency, Sensory neuropathy, Sensorineural hearing loss, and Skeletal dysplasia) and Leigh syndrome to isolated nonsyndromic cataracts. Here, we describe the phenotypic and genetic spectrum of Korean patients with IARS2-related disorders. Materials and Methods: Using whole-exome sequencing followed by Sanger sequencing, we identified five patients with IARS2 mutations. Their medical records and brain magnetic resonance images were reviewed retrospectively. Results: All five patients presented with developmental delay or regression before 18 months of age. Three patients had bilateral cataracts, but none had hearing loss or sensory neuropathy. No evidence of skeletal dysplasia was noted, but two had short stature. One patient had cardiomyopathy and another exhibited renal tubulopathy and hypoparathyroidism. Their brain imaging findings were consistent with Leigh syndrome. Interestingly, we found the recurrent mutations p.R817H and p.V105Dfs*7 in IARS2. Conclusion: To our knowledge, this is the first report of Korean patients with IARS2-related disorders. Our findings broaden the phenotypic and genotypic spectrum of IARS2-related disorders in Korea and will help to increase clinical awareness of IARS2-related neurodegenerative diseases.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.1
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• pp.121-132
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• 2008

Objective : This study was performed to examine the patterns of inpatients that had visited Dept. of Dermatology Hospital of Oriental Medicine, Dongguk University. Methods : We analysed statistic study in 106 patients, who had admitted to the Dept. of Dermatology, Ophthalmology & Otorhinolaryngology Hospital of Oriental Medicine, Dongguk University from July, 2005 to January, 2008. Results : The results were as follows; 1. Males were 50.94% and females were 49.06%. 2. Distribution of aging was 18.87% in twenties and 17.92% in fifties. 3. Common disease group were Facial palsy(33.96%); Atopic dermatitis(21.7%); Tinnitus(7.55%); Sudden Sensorineural Hearing loss(4.72%); Sore throat(5.66%). 4. Average age of Facial palsy patients was 50.9 years old, average hospitalized period were 10.47days and subjective satisfaction rate was 2.56 points on the basis of 4 points. 5. Average age of Atopic dermatitis patient's average age was 22.22 years old, average hospitalized period were 8.35days and subjective satisfaction rate was 3.44 points on the basis of 4 points. 6. 47.2% of all patient were admitted into the hospital on 1st or 2nd outpatient service and 44% of Facial palsy patient were admitted into the hospital via emergency room. 7. All patient's average hospitalized period were 7.5 days. 8. All patient's subjective satisfaction rate were 2.97 points on the basis of 4 points. Conclusion : This study suggests that oriental medical treatments is especially popular in facial palsy and atopic dermatitis. We have to take steps for effective management and treatment for special diseases and ages.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.14 no.2
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• pp.134-145
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• 2001

Introduction: Noises in the ear, whether real or imagined, are called tinnitus. Subjective causes of tinnitus(which is heard only by the patient) are extremely common and the majority of them are treated conservatively. For certain individuals their tinnitus is a major handicap; for others a trivial concern. The most common from of subjective tinnitus is a rushing, hissing or buzzing noise; it is frequently associated with sensorineural heanng loss. The patient may be unaware of the hearing loss, especially if it is a high frequency deficit of moderate severity. The character of the tinnitus may give a clue to the etiology. But the patient often has difficulty in explaining his/her tinnitus in absolute terms, as they have no other tinnitus with which to compare it but their own Tinnitus, like pain, is a subjective state and trying to objectively assess the severity is problematic. Audiological techniques to match subjective loudness to machine-produced noise may offer some help, in that sound intensity matches can bear little correspondence to subjective complaint. In spite of many studies, most patients presently seen complaining of tinnitus are told by their doctors that there is no treatment and that they will have to learn to live with this symptom. Objectives: To perform a clinical analysis of tinnitus and estimate the efficacy of Oriental Medical treatment according to the Byeonjeung(辨證). Subject: We studied 34 patients with complaints of tinnitus who had visited Pundang Cha Oriental Medicine Hospital Department of Otorhinolaryngology from March 1998 to February 2000. All of them had been treated 2 or 3 times a week with acupuncture treatment and had taken herbs according to the Byeonjeung(辨證) method. It was therefore possible for me to know whether their symptoms improved or not. Parameters Observed and Method: We treated them with acupuncture & herb-medication. Sometimes we gave them moxibustion or negative therapy with bloodletting at the acupuncture points(耳門, 聽宮, 聽會). Parameters Observed 1) Distribution of age & sex 2) Chief complaints 3) The sites of tinnitus 4) The quality of tinnitu 5) The duration of disease 6) The problem induced tinnitus 7) Factors increasing disease severity 8) The classification of the Byeonjeung(辨證) 9) The efficacy of treatments Results: 1. Age and sex distribution: The most common occurrence was found in males in their twenties: 6 males($17.7\%$), and in females in their thirties and over sixty: 8 females($23.5\%$). Total patient numbers for men and women were 20 men($58.8\%$), 14 women ($41.2\%$). 2. The most frequent major complaints were hearing disturbances related to tinnitus; and dizziness with tinnitus; each comprising 10 cases($29.4\%$). There were also 7 patients($20.6\%$) with only tinnitus. 3. Tinnitus sites: 13($38.2\%$) said that they felt tinnitus in both ears, equally. In the right ear, 9($26.5\%$), in the left, 6($17.7\%$). 4. The most frequent descriptive symptoms of tinnitus were: humming, hissing, buzzing etc. 5. The duration of disease. 14cases($41.2\%$) had a duration of less than 1 year. 6. 15cases($44.1\%$) complained that it was hard to watch TV or make a phone call because of tinnitus. 10 cases($29.4\%$) complained about depression. 7. Factors increasing severity of tinnitus: ⅰ) fatigue: 18cases($52.9\%$) ⅱ) stress/ tension: 10 cases($29.4\%$) ⅲ) alcohol and tobacco: 5cases($l4.7\%$) 8. Classification through Byeonjeung : ⅰ) 19 cases($55.9\%$) were classified as showing Deficiency syndrome. ⅱ) 15 cases($44.l\%$) were classified as showing Excess syndrome. The deficiency of Qi was 7($20.6\%$), deficiency of Xue, 8($23.5\%$) and insufficiency of the Kidney Yin & Yang, 4($11.8\%$). The flare of Liver fire was 8($23.5\%$) and phlegm-fire, 7($20.6\%$), 9. The efficacy of treatments showed: an improvement in 17cases($50.0\%$); no real improvement or changes in 13 cases($38.2\%$); and some worsening in 4 cases($11.8\%$). In the group with deficiency in Qi, 4($57.1\%$) improved, 1($14.3\%$) showed no change and 2($28.6\%$) were aggravated. In the cases of deficiency in Xue, 6($75.0\%$) improved, 2($25.0\%$) showed no change. In the cases of insufficiency of Kidney Yin & Yang, 3($75.0\%$) showed no change and 1($25.0\%$) were aggravated. In the group of flare of Liver fire, 4($50.0\%$) improved, 3($37.5\%$) no change and 1($12.5\%$) were aggravated. In the cases of phlegm-fire, 3($42.9\%$) improved, 4($57.1\%$) showed no change. Conclusion: We would recommend that any further studies of tinnitus utilize trial treatments of longer than 2 months duration, as any positive effects observed in our study showed that improvement occurred fairly slowly. And we suggest that this study could be utilized as a reference for clinical Oriental Medical treatment of tinnitus. If we try to apply music or sound therapy treatment properly combined with ours, we expect it to provide psycological stability in addition to inducing masking effects, even though it may not directly decrease or completely remove tinnitus.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.164-175
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• 2001

Purpose : Alport syndrome is a hereditary nephrotic disease characterized by progressive nephrotic symptom, sensorineural hearing loss, ophthalmic abnormality, typical microscopic findings, and familial occurrence. In this study, we tried to find the risk factors related with its prognosis by taking a close observation on clinical symptoms of children with Alport syndrome reviewing retrospectively. Materials & methods : We chose children diagnosed as Alport syndrome in renal biopsy during 20 years(from 1980, Jan. until 1999, Dec.) who could receive follow up studies in tile department of pediatrics. They were divided into two groups by comparing renal function at the time of diagnosis and at current status. We compared several clinical aspects in them, and applied nonparametric test for statistical analysis. Results : The sex ratio(male:female) of 24 children was 3:1. The most common clinical symptom presented at their first visit was gross hematuria. Among those 24 children, 11 cases($46\%$) of progressing into chronic renal failure(Group II) were observed. Hypertension, proteinuria and edema were seen much frequently in group II. The level of serum protein, albumin, and creatinine clearance were decreased while BUN, creatinine were relatively increased. All the results were statistically significant. Conclusion Clinically significant risk factors related to prognosis in Alport syndrome were the presence of hypertension, edema, and proteinuria at the time of diagnosis. Also, the level of serum protein, albumin, BUN, creatinine, and glomerular filtration rate were proved to be important factors in predicting prognosis. We believe that studies on these possible risk factors would be of great help in treating and predicting prognosis of children suffering with Alport syndrome. (J Korean Soc Pediatr Nephrol 2001;5 : 164-75)

• Childhood Kidney Diseases
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• v.4 no.1
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• pp.48-56
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• 2000

Purpose: Alport SD., the most common herectitary rephriris, is a renal disease with rapid progression. Deafness, ocular abnormalities and a specific EM finding may be associated in addition to a family history. We have aralyged retrospectively. Methods: We observed 12 children with Alport syndrome who were diagnosed at Dept. of pediatrics in Kyunghee Univ., College of Medicine, from Apr. 1991 until Jun. 1999. We used four criteria for diagnosis: renal disease, family history, deafness or eye abnormalities, and a specific finding in electron microscopy Results: 2 of 12 patients had all features of the four diagnostic criteria. We could not trace an exact family history in 3 patients, and 6 patients did not exhibit deafness or eye abnormality. One could not have renal biopsy because offer chronic renal failure. Other three criteria were observed in her. The ratio of male to female observed was 1:2 respectively and the mean age of initial renal symptom was 5.6 years. 9 of 12 patients had a family history of renal disease. In the audiogram and ocular examination for 11 of 12 cases, sensorineural hearing loss was observed in 6 and ocular abnormality in 2 cases. In electron microscopic finding, irregular thickness of the capillary basement membranes with lamination of lamina densa and foot process obliteration was noted in 9 of 11 and thin basement membrane with splitting and foot process obliteration was noted in the other 2. The mean period of follow-up was 3 6/12 years. And one patient developed the chronic renal failure until now and had kidney transplantation. Conclusion: For the diagnosis of Alport syndrome, the following four diagnostic criteria are very important : renal disease, family history, deafness or eye abnormalities, and a specific finding on electron microscopy. We expect that more patients can be detected through the analysis of these characteristics.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.1
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• pp.25-30
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• 2023

Leigh syndrome is a rare progressive neurodegenerative mitochondrial disorder with clinical and genetic heterogeneity. Recently, balletic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes from Leigh and West syndrome to a rare syndrome CAGSSS characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome (OMIM#616007). We describe a child with Korean Leigh syndrome with urologic manifestations resulting from a compound heterozygote mutation in IARS2. A 5-year-old girl visited the emergency room with a complaint of abdominal pain accompanied by abdominal distension. Abdominal-pelvic CT showed a markedly distended urinary bladder without definite obstructive lesions. She was diagnosed with neurogenic bladder dysfunction based on a urodynamic study. She had global delayed development due to neurologic regression after 6 months of age and a history of bilateral cataract surgery at the age of 2 years. Her brain magnetic resonance imaging showed symmetrically increased signal intensities in the bilateral putamen and caudate nuclei with diffuse cerebral atrophy. No gene variants were identified through whole-mitochondrial genome analysis. Whole exome sequencing was performed for diagnosis, and compound heterozygous pathogenic variants were identified in IARS2: c.2446C>T (p. Arg816Ter) and c.2450G>A (p. Arg817His). To the best of our knowledge, this is the first case report of bladder dysfunction manifestation in a patient with IARS2-related Leigh syndrome. Thus, it broadens the clinical and genetic spectrum of IARS2-associated diseases.