• Clinical and Experimental Pediatrics
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• v.51 no.6
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• pp.634-639
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• 2008

Purpose : There has been considerable disagreement regarding the most appropriate dosage of gonadotropin-releasing hormone agonist in cases of central precocious puberty. The aim of this study was to determine the appropriate dosage for suppression of the puberty in girls with central precocious or early puberty. Methods : Twenty-two girls with early puberty were randomly subjected to 3 types of dosages of leuprolide acetate for at least 6 months. The number of cases in groups 1, 2, and 3 were 7, 7, and 8, and dosages were 70, 90, and $110{\mu}g/kg/-month$, respectively. Height, weight, bone age, Tanner stage of breast development, and serum levels of LH, FSH, estradiol, and progesterone were measured before treatment and after 6 months of treatment. The number of cases of puberty suppression was compared using a modified puberty suppression score with a nonparametric chi-square test. Results : There were no significant differences of chronologic and bone ages among the groups. There was a significant decrease in height SDS gain after 6 months in group 3 (P<0.05) compared with groups 1 and 2. Serum levels of LH, FSH, estradiol and progesterone were all significantly decreased after treatment in all 3 groups (P<0.05). The number of cases of puberty suppression in each group were 4 (57%), 5 (71%), and 8 (100%). There was a significantly increased proportion of suppression of puberty in group 3 (P<0.05). Conclusion : It was necessary to use a higher dose of gonadotropin-releasing hormone agonist to suppress early puberty in girls; however further longitudinal study will be needed for their prognosis of final adult height.

• Investigative Magnetic Resonance Imaging
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• v.8 no.1
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• pp.32-41
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• 2004

Purpose : To measure the NMR relaxation properties of MnPC, to observe the characteristics of liver enhancement patterns on MR images in experimentally implanted rabbit VX2 tumor model, and to estimate the possibility of tissue specific contrast agent for MnPC in comparison with the hepatobiliary agent. Materials and Methods : Phthalocyanine (PC) was chelated with paramagnetic ions, manganese (Mn). 2.01 g (5.2 mmol) of phthalocyanine was mixed with 0.37 g (1.4 nlmol) of Mn chloride at $310^{\circ}C$ for 36 hours and then purified by chromatography ($CHCl_3:\;CH_3OH=98:2$, volume ratio) to obtain 1.04 g $(46\%)$ of MnPC (molecular weight = 2000 daltons). The T1/T2 relaxivity (R1/R2) for MnPC were determined at a 1.5 T (64 MHz) MR spectrometer. VX2 tumor model was experimentally implanted in the liver parenchyma of rabbits. All MR studies were performed on 1.5 T. The human extremity radio frequency coil of a bird cage type was employed. MR images were acquired at 17 to 24 days after VX2 carcinoma implantation.4 mmol/kg MnPC and 0.01 mmol/kg Mn-DPDP were injected via the ear vein of rabbits. T1-weighted images were obtained with spin-echo (TR/TE=516/14 msec) and fast multiplanar spoiled gradient recalled (TR/TE : 80/4 msec, $60^{\circ}$ flip angle) pulse sequence. Fast spin-echo (TR/TE=1200/85 msec) was used to obtain the T2-weighted images. Results : The value of T1/T2 relaxivity (R1/R2) of MnPC was $7.28\;mM^{-1}S^{-1}$ and $55.56\;mM^{-1}S^{-1}$ respectively at 1.5 T (64 MHz). Because the T2 relaxivity of MnPC that bonded strongly, covalently manganese with phthalocyanine was very high, the signal intensity of liver parenchyma was decreased on postcontrast T2-weighted images and we could easily distinguish the VX2 carcinoma within the liver parenchyma. When MnPC was administrated intravenously, the tumor margin delineation was more remarkable than Mn-DPDP-enhanced images. The enhancement of liver parenchyma with MnPC persisted at relatively high levels over at least one hour after injection of the contrast agents. Conclusion : The hepatic uptake and biliary excretion of MnPC, which are similar to Mn-DPDP, suggest that this agent is a new liver-specific agent. Also, MnPC seems to be used as a dual contrast agent (T1 and T2) with high T2 relaxivity. However, it is warranted that MnPC needs further investigation as a potential contrast agent for MR imaging of the liver. That is, further characterizations of MnPC are needed in vivo and in vitro before clinical trials. The diagnostic potential of MnPC will also have to be examined more in the animal models of additional types.

• Investigative Magnetic Resonance Imaging
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• v.8 no.2
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• pp.79-85
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• 2004

Purpose : To evaluate the usefulness and reproducibility of $^1H$ MRS in different 1.5 T MR machines with different coils to compare the SNR, scan time and the spectral patterns in different brain regions in normal volunteers. Materials and Methods : Localized $^1H$ MR spectroscopy ($^1H$ MRS) was performed in a total of 10 normal volunteers (age; 20-45 years) with spectral parameters adjusted by the autoprescan routine (PROBE package). In all volunteers, MRS was performed in a three times using conventional MRS (Signa Horizon) with 1 channel coil and upgraded MRS (Echospeed plus with EXCITE) with both 1 channel and 8 channel coil. Using these three different machines and coils, SNRs of the spectra in both phantom and volunteers and (pre)scan time of MRS were compared. Two regions of the human brain (basal ganglia and deep white matter) were examined and relative metabolite ratios (NAA/Cr, Cho/Cr, and mI/Cr ratios) were measured in all volunteers. For all spectra, a STEAM localization sequence with three-pulse CHESS $H_2O$ suppression was used, with the following acquisition parameters: TR=3.0/2.0 sec, TE=30 msec, TM=13.7 msec, SW=2500 Hz, SI=2048 pts, AVG : 64/128, and NEX=2/8 (Signa/Echospeed). Results : The SNR was about over $30\%$ higher in Echospeed machine and time for prescan and scan was almost same in different machines and coils. Reliable spectra were obtained on both MRS systems and there were no significant differences in spectral patterns and relative metabolite ratios in two brain regions (p>0.05). Conclusion : Both conventional and new MRI systems are highly reliable and reproducible for $^1H$ MR spectroscopic examinations in human brains and there are no significant differences in applications for $^1H$ MRS between two different MRI systems.

• Investigative Magnetic Resonance Imaging
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• v.8 no.2
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• pp.100-108
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• 2004

Purpose : Early degeneration of articular cartilage is accompanied by a loss of glycosaminoglycan (GAG) and the consequent change of the integrity. The purpose of this study was to biochemically quantify the loss of GAG, and to evaluate the $Gd(DTPA)^{2-}$-enhanced, and T1, T2, rho relaxation map for detection of the early degeneration of cartilage. Materials and Methods : A cartilage-bone block in size of $8mm\;\times\;10mm$ was acquired from the patella in each of three pigs. Quantitative analysis of GAG of cartilage was performed at spectrophotometry by use of dimethylmethylene blue. Each of cartilage blocks was cultured in one of three different media: two different culture media (0.2 mg/ml trypsin solution, 1mM Gd $(DTPA)^{2-}$ mixed trypsin solution) and the control media (phosphate buffered saline (PBS)). The cartilage blocks were cultured for 5 hrs, during which MR images of the blocks were obtained at one hour interval (0 hr, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr). And then, additional culture was done for 24 hrs and 48 hrs. Both T1-weighted image (TR/TE, 450/22 ms), and mixed-echo sequence (TR/TE, 760/21-168ms; 8 echoes) were obtained at all times using field of view 50 mm, slice thickness 2 mm, and matrix $256\times512$. The MRI data were analyzed with pixel-by-pixel comparisons. The cultured cartilage-bone blocks were microscopically observed using hematoxylin & eosin, toluidine blue, alcian blue, and trichrome stains. Results : At quantitation analysis, GAG concentration in the culture solutions was proportional to the culture durations. The T1-signal of the cartilage-bone block cultured in the $Gd(DTPA)^{2-}$ mixed solution was significantly higher ($42\%$ in average, p<0.05) than that of the cartilage-bone block cultured in the trypsin solution alone. The T1, T2, rho relaxation times of cultured tissue were not significantly correlated with culture duration (p>0.05). However the focal increase in T1 relaxation time at superficial and transitional layers of cartilage was seen in $Gd(DTPA)^{2-}$ mixed culture. Toluidine blue and alcian blue stains revealed multiple defects in whole thickness of the cartilage cultured in trypsin media. Conclusion : The quantitative analysis showed gradual loss of GAG proportional to the culture duration. Microimagings of cartilage with $Gd(DTPA)^{2-}$-enhancement, relaxation maps were available by pixel size of $97.9\times195\;{\mu}m$. Loss of GAG over time better demonstrated with $Gd(DTPA)^{2-}$-enhanced images than with T1, T2, rho relaxation maps. Therefore $Gd(DTPA)^{2-}$-enhanced T1-weighted image is superior for detection of early degeneration of cartilage.

• The Korean Journal of Nuclear Medicine
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• v.33 no.3
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• pp.298-305
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• 1999

Purpose: N-(3-[$^{18}F$]Fluoropropyl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-iodophenyl)nortropane [$^{18}F$]FP-CIT) has been shown to be very useful for imaging the dopamine transporter. However, synthesis of this radiotracer is somewhat troublesome. In this study, we used a new method for the preparation of [$^{18}F$]FP-CIT to increase radiochemical yield and effective specific activity. Materials and Methods: [$^{18}F$]FP-CIT was prepared by N-alkylation of nor-${\beta}$-CIT (2 mg) with 3-bromo-1-[$^{18}F$]fluoropropane in the presence of $Et_3N$ (5-6 drops of $DMF/CH_3CN$, $140^{\circ}C$, 20 min). 3-Bromo-1-[$^{18}F$]fluoropropane was synthesized from $5{\mu}L$ of 3-bromo-1-trifluoromethanesulfonyloxypropane (3-bromopropyl-1-triflate) and $nBu_4N^{18}F$ at $80^{\circ}C$. The final compound was purified by reverse phase HPLC and formulated in 13% ethanol in saline. Results: 3-Bromo-1-[$^{18}F$]fluoropropane was obtained from 3-bromopropyl-1-triflate and $nBu_4N^{18}F$ in 77-80% yield. N-Alkylation of nor-${\beta}$-CIT with 3-bromo-1-[$^{18}F$]fluoropropane was carried out at $140^{\circ}C$ using acetonitrile containing a small volume of DMF as the solvents. The overall yield of [$^{18}F$]FP-CIT was 5-10% (decay-corrected) with a radiochemical purity higher than 99% and effective specific activity higher than the one reported in the literature based on their HPLC data. The final [$^{18}F$]FP-CIT solution had the optimal pH (7.0) and it was pyrogen-free. Conclusion: In this study, 3-bromopropyl-1-triflate was used as the precursor for the [$^{18}F$]fluorination reaction and new conditions were developed for purification of [$^{18}F$]FP-CIT by HPLC. We established this new method for the preparation of [$^{18}F$]FP-CIT, which gave high effective specific activity and relatively good yield.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.42-48
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• 2007

Purpose: The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using $[^{18}F]FDG$ small animal PET and clinical CT. Materials and Methods: The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at $30^{\circ}C$. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq $[^{18}F]FDG$ and compared pattern of $[^{18}F]FDG$ uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, $[^{18}F]FDG$ image was obtained and fused with anatomical clinical CT image. Results: Average blood glucose concentration in normal mice were $128.0{\pm}23.87$ and $86.0{\pm}21.65\;mg/dL$ in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was $8.6{\pm}0.48$ and $12.1{\pm}0.63$ in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, $[^{18}F]FDG$ image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in $[^{18}F]FDG$ small animal PET image was confirmed by fusion image using clinical CT. Conclusion: Tumor imaging in small animal lung region with $[^{18}F]FDG$ small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during $[^{18}F]FDG$ uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.9-15
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• 2007

Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

• Pediatric Infection and Vaccine
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• v.10 no.1
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• pp.71-80
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• 2003

Purpose : Four kinds of Haemophilus influenzae type b protein conjugate vaccines, PRPD, PRP-T, PRP-OMP and PRP-CRM197, have been developed, and PRP-T vaccines are currently produced by two manufacturer, $ActHib^{(R)}$ by Aventis and $Hiberix^{TM}$ by GlaxoSmith-Kline Biologicals. The purpose of this study is to evaluate the immunogenicity and safety of $Hiberix^{TM}$ in Korean infants. Methods : Seventy-three healthy infants(43 male infants) were recruited for this study after parental informed consent was obtained. Each infant was vaccinated at 2, 4 and 6 months of age with the study vaccine. At each visit, infants were also immunized with DTaP, trivalent oral polio vaccine and hepatitis B vaccine when indicated. The serum anti-PRP antibody was measured at prevaccination, 2 month later after the 2nd dose, and 1 month later after the 3rd dose by the ELISA method. The local and systemic adverse reactions of vaccination were monitored for 3 consecutive days after each immunization. Immunogenicity of vaccine was evaluated in infants who received all the scheduled immunization and the adverse reactions were evaluated for infants who received at least one dose of the study vaccine. Results : Among seventy three infants, enrolled in this study; sixty three(37 male infants) completed all the scheduled immunizations. The geometric mean titer(GMT) of anti-PRP antibodies at prevaccination was 0.17 ${\mu}g/mL$(95% confidence interval[CI]; 0.13~0.22). The GMT of anti-PRP antibodies increased to 4.14 ${\mu}g/mL$(95% CI; 2.65~6.48) at 2 month later after the 2nd dose of PRP-T and 14.65 ${\mu}g/mL$(95% CI; 10.83~19.81) at 1 month later after the 3rd dose. Anti-PRP antibody ${\geq}0.15$ ${\mu}g/mL$, was observed in 98.4%(95% CI; 91.8~100) after 2 doses and 100%(95% CI; 100~100) after 3 doses. Anti-PRP antibody ${\geq}1.0$ ${\mu}g/mL$, was obtained in 77.8%(95% CI; 67.5~88.0) after 2 doses, and 98.4%(95% CI; 95.3~100) after 3 doses. Most of the adverse reaction after vaccination were mild. Irritability, the most common systemic reaction, was observed in 45.5%, followed by drowsiness(30.5%), poor feeding(26.7%) and fever(5.6%). Among the local reactions tenderness was observed in 7.9%, redness(${\geq}5$ mm) in 2.8% and swelling(${\geq}5$ mm) in 1.8%. Conclusion : The PRP-T vaccine used in this study was highly immunogenic and safe in Korean young infants. The finding that high GMT and high frequency of infants with a protective titer achieved after 2 doses is consistent with the previous studies which were done with a PRP-T vaccine of other manufacturer. This study suggests that the immunization schedule of PRP-T vaccine for Korean infants may need re-evaluation.

• Journal of Preventive Medicine and Public Health
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• v.32 no.2
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• pp.123-129
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• 1999

Objectives: This study was performed to investigate sweets of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), glutathione S-transferase M1 (GSTT1), cytochrome P450 1A1 (CYP1A1) and cytoehrome P450 2E1 (CYP2E1) on lung cancer development. Methods: Ninety-eight lung cancer patients and 98 age-sex matched non-cancer patients hospitalized in Chungbuk National University Hospital form March 1997 to August 1998, were the subjects of this case-control study. Direct interview was done and genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. Effects of the polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1, lifestyle factors including smoking, and their interactions on lung rancor were statistically analyzed. Results: GSTM1 was deleted in 67.01% of the cases and 58.16% of the controls, and the odds ratio(95% CI) was 1.46(0.82-2.62). GSTT1 deletion was 58.76% for the lung cancer patients and 50.00% for the controls[OR:1.43(0.81-2.51)]. The frequencies of lle/lle, lle/Val and Val/Val of the CYP1A1 polymorphisms were 59.18-18%, 35.71%, and 5.10% for the cases, and 52.04%, 45.92%, 2.04% for the controls, respectively. Risk of lung cancer was not associated with polymorphism of CYP1A1 ($x^2trend=0.253$, p-value>0.05). The respective frequency of c1/c1 c1/c2, c2/c2 genotypes for CYP2E1 were 50.00%, 42.86%, 7.14% for the lung cancer patients, and 66.33%, 30.61%, 3.06% for the controls $(x^2trend=5.783,\;p<0.05)$. c2 allele was a significant risk factor for lung cancer. We also observed a significant association of cigarette smoking history with lung cancer risk. The odds ratio(95% Cl) of cigarette smoking was 3.03(1.58-5.81). In multiple logistic analysis including genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1, and smoking habit, only snaking habit came out to be a significant risk factor for lung cancer. Conclusion: Genetic polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 are not so strongly associated with lung cancer as lifestyle factors including cigarette smoking.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.222-230
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• 2005

Purpose : ARC syndrome refers to an association of arthrogryposis, renal tubular dysfunction, and cholestasis. The VPS33B gene was recently identified as the causative gene. So far, 41 cases of ARC syndrome have been reported worldwide, and it has rarely been reported in Korea. This study was conducted to report the clinical findings of seven ARC syndrome cases in Korean children, focusing especially on renal tubular dysfunction. Methods : The hospital records of 7 cases diagnosed as ARC syndrome at Severance Hospital between Mar. 1995 and Aug. 2005 were reviewed and analyzed. Results : Of the 7 cases, 4 were boys and 3 were girls. Six patients(85$\%$) were born with normal birth weight at term, and one was born at preterm. All cases presented with cholestasis and severe jaundice. According to the type of arthrogryposis described by Brown et al, type 3 and 4 were found in 2 patients and type,6, 7, and the undistributed type in one patient respectively. Other associated clinical findings were as follows : failure to thrive in 6(85$\%$), lax skin in 5(71$\%$), and gray platelet syndrome in 4(57$\%$). Urine analysis revealed 6 cases(85$\%$) with proteinuria, 3(43$\%$) with hematuria, 5(71$\%$) with glycosuria, 2(29$\%$) with phosphaturia and 2(29$\%$) with calciuria. Serum electrolytes showed 4 cases(57$\%$) with hyponatremia, 3(43$\%$) with hypokalemia, and 1(14$\%$) with creatinine elevation. Renal tubular dysfunctions were diagnosed as renal tubular acidosis in 6 cases(85$\%$), nephrogenic diabetes insipidus in 2(29$\%$), and Fanconi syndrome in 2(29$\%$). During the follow-up period, 2(29$\%$) had no treatment, 5(85$\%$) had continuous supplementation to correct the electrolyte imbalance and acidosis, and 1(14$\%$) had dialysis. Only one patient had a family history of ARE syndrome in a sibling. Four cases(57$\%$) were diagnosed at the mean age of 8.2 months, and one case was lost during follow-up. Ages of the survived 2 cases were 13 and 25 months, respectively. Conclusion : The rare disease of ARC syndrome Is associated with severe renal dysfunction. However, this study revealed that the renal manifestation of ARC syndrome in Korean children is relatively mild and survival rate is higher than that of previous studies. Contrary to previous reports, this study showed that familial cases are rare and sporadic occurence is possible in Korea. Thus, the diagnosis of this syndrome requires a careful evaluation of the venal function in cases of congenital arthrogryposis, and a mandatory genetic counseling of affected family for prevention of familial occurance. (J Korean Soc Pediatr Nephrol 2005;9:222-230)