Imaging Findings of a Malignant Rhabdoid Tumor in the Stomach:A Case Report

A malignant rhabdoid tumor is an aggressive tumor that occurs mainly in the kidney of infants and children. When it occurs in extrarenal sites, it is referred to as an extrarenal malignant rhabdoid tumor. Although a few cases of malignant rhabdoid tumor occuring in the central nervous system, liver, brain, skin, and soft tissue have been reported, it is rarely observed in the stomach. We report the imaging findings of a malignant rhabdoid tumor of the stomach that mimicked a gastric lymphoma in a patient who presented with melena.

Imaging Findings of a Malignant Rhabdoid Tumor in the Stomach:A Case Report

A malignant rhabdoid tumor is an aggressive tumor that occurs mainly in the kidney of infants and children. When it occurs in extrarenal sites, it is referred to as an extrarenal malignant rhabdoid tumor. Although a few cases of malignant rhabdoid tumor occuring in the central nervous system, liver, brain, skin, and soft tissue have been reported, it is rarely observed in the stomach. We report the imaging findings of a malignant rhabdoid tumor of the stomach that mimicked a gastric lymphoma in a patient who presented with melena.

Imaging Findings of Primary Adrenal Leiomyosarcoma: A Case Report

Leiomyosarcoma is a malignant tumor that typically originates from either the uterus or the retroperitoneum. Furthermore, primary adrenal leiomyosarcoma is an extremely rare condition. Owing to its radiological non-specificity, differentiating leiomyosarcoma from other tumor types in the adrenal gland is difficult. We report the imaging findings of a primary adrenal leiomyosarcoma in a patient who presented with left upper quadrant abdominal pain, which increased by more than 1 cm in diameter in two years. Primary adrenal leiomyosarcoma was diagnosed considering the subsequent surgical and histopathologic findings.

Imaging Findings of Primary Adrenal Leiomyosarcoma: A Case Report

Leiomyosarcoma is a malignant tumor that typically originates from either the uterus or the retroperitoneum. Furthermore, primary adrenal leiomyosarcoma is an extremely rare condition. Owing to its radiological non-specificity, differentiating leiomyosarcoma from other tumor types in the adrenal gland is difficult. We report the imaging findings of a primary adrenal leiomyosarcoma in a patient who presented with left upper quadrant abdominal pain, which increased by more than 1 cm in diameter in two years. Primary adrenal leiomyosarcoma was diagnosed considering the subsequent surgical and histopathologic findings.

Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry

The main purpose of newborn screening is to diagnose genetic, metabolic, and other inherited disorders, at their earliest to start treatment before the clinical manifestations become evident. Understanding and tracing the biochemical data obtained from tandem mass spectrometry is vital for early diagnosis of metabolic diseases associated with such disorders. Accordingly, it is important to focus on the entire diagnostic process, including differential and confirmatory diagnostic options, and the major factors that influence the results of biochemical analysis. Compared to regular biochemical testing, this is a complex process carried out by a medical physician specialist. It is comprised of an integrated program requiring multidisciplinary approach such as, pediatric specialist, expert scientist, clinical laboratory technician, and nutritionist. Tandem mass spectrometry is a powerful tool to improve screening of newborns for diverse metabolic diseases. It is likely to be used to analyze other treatable disorders or significantly improve existing newborn tests to allow broad scale and precise testing. This new era of various screening programs, new treatments, and the availability of detection technology will prove to be beneficial for the future generations.

Erratum to: Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry

The original published article contains an inaccurate statement in Acknowledgements section.

Serum Globotriaosylceramide Assay as a Screening Test for Fabry Disease in Patients with ESRD on Maintenance Dialysis in Korea

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.

Seven-year experience with inherited metabolic disorders screening by tandem mass spectrometry

PURPOSE: In recent years, many countries have adopted newborn screening programs that use tandem mass spectrometry (MS/MS) to screen and the number of diseases screened has also increased. We began screening for inherited metabolic disorders using MS/MS in April, 2001. Our goal was to determine the overall prevalence of metabolic disorders and to assess the effectiveness of newborn screening by MS/MS in Korea. METHODS: From April, 2001 to December, 2007, we screened newborns and high risk groups using MS/MS. Acylcarnitines and amino acids were extracted and butylated and were introduced into the inlet of MS/MS. Confirmatory testing including a repeat newborn screening, and urine organic acid and plasma amino acid analysis were performed on a case-by-case basis. RESULTS: The total number of screened subjects 284,933 which comprised 251,799 neonates and 33,134 high risk subjects. The recall rate was 0.4% (1158 tests) and true positive cases were 117 (0.04%). Confirmed metabolic disorders (newborn/high risk group) were as follows; 78 (25/53) amino acid disorders, 27 (16/11) organic acid disorders, and 12 (5/7) fatty acid oxidation disorders. The estimated prevalence of inherited metabolic diseases in newborns was 1:5,000 and that in the total group was 1:2,000. CONCLUSION: Newborn screening by MS/MS improved the detection of many inherited metabolic disorders. We therefore propose that all newborns be screened by a MS/MS national program and followed-up using a systemic organization strategy.

Short-Term Efficacy of Enzyme Replacement Therapy in Korean Patients with Fabry Disease

Fabrazyme has been widely used for treatment of Fabry disease since its approval by the U.S. Food and Drug Administration in 2003. This study was undertaken to assess the short-term efficacy and safety of enzyme replacement therapy (ERT) for Fabry disease in Korea. Eight male patients and three female symptomatic carriers aged 13 to 48 yr were included. Fabrazyme was administered by intravenous infusion at a dose of 1 mg/kg every 2 weeks. Plasma and urine globotriaosylceramide (GL-3) levels, serum creatinine, creatinine clearance, and 24-hr urine protein levels were measured every 3 months. Kidney biopsies, ophthalmologic exams, and pure tone audiometry were performed before and 1 yr after ERT. Kidney function, including serum creatinine, creatinine clearance, and the 24-hr urine protein level, remained stable during ERT. Plasma and urine GL-3 levels were reduced within 3 to 6 months of ERT initiation. Microvascular endothelial deposits of GL-3 were decreased from renal biopsy specimens after 1 yr of treatment. The severity of sensorineural hearing loss and tinnitus did not improve after ERT. ERT is safe and effective in stabilizing renal function and clearing microvascular endothelial GL-3 from kidney biopsy specimen in Korean patients with Fabry disease.

PHEX Gene Mutations and Genotype-Phenotype Analysis of Korean Patients with Hypophosphatemic Rickets

X-linked hypophosphatemic rickets (XLH) results from mutations in the PHEX gene. Mutational analysis of the PHEX gene in 15 unrelated Korean patients with hypophosphatemic rickets revealed eight mutations, including five novel mutations, in nine patients: two nonsense mutations, two missense mutations, one insertion, and three splicing acceptor/donor site mutations. Of these, c.64G>T, c.1699C>T, c.466_467 insAC, c.1174-1G>A, and c.1768+5G>A were novel mutations. To analyze the correlation between genotype and phenotype, phenotypes were compared between groups with and without a mutation, in terms of mutation location, mutation type, and sex. Skeletal disease tended to be more severe in the group with a mutation in the C-terminal half of the PHEX gene, but no genotype-phenotype correlation was detected in other comparisons. Further extensive studies of the PHEX gene mutations and analyses of the genotype-phenotype relationships are required to understand PHEX function and the pathogenesis of XLH.

Determination of plasma C16-C24 globotriaosylceramide (Gb3) isoforms by tandem mass spectrometry for diagnosis of Fabry disease

PURPOSE: A simple, rapid, and highly sensitive analytical method for Gb3 in plasma was developed without labor-extensive pre-treatment by electrospray ionization MS/MS (ESI-MS/MS). Measurement of globotriaosylceramide (Gb3, ceramide trihexoside) in plasma has clinical importance for monitoring after enzyme replacement therapy in Fabry disease patients. The disease is an X-linked lipid storage disorder that results from a deficiency of the enzyme ??-galactosidase A (alpha-Gal A). The lack of alpha-Gal A causes an intracellular accumulation of glycosphingolipids, mainly Gb3. METHODS: Only simple 50-fold dilution of plasma is necessary for the extraction and isolation of Gb3 in plasma. Gb3 in diluted plasma was dissolved in dioxane containing C17:0 Gb3 as an internal standard. After centrifugation it was directly injected and analyzed through guard column by in combination with multiple reaction monitoring mode of ESI-MS/MS. RESULTS: Eight isoforms of Gb3 were completely resolved from plasma matrix. C16:0 Gb3 occupied 50% of total Gb3 as a major component in plasma. Linear relationship for Gb3 isoforms was found in the range of 0.001-1.0 microgram/mL. The limit of detection (S/N=3) was 0.001 microgram/mL and limit of quantification was 0.01 microgram/mL for C16:0 Gb3 with acceptable precision and accuracy. Correlation coefficient of calibration curves for 8 Gb3 isoforms ranged from 0.9678 to 0.9982. CONCLUSION: This quantitative method developed could be useful for rapid and sensitive 1st line Fabry disease screening, monitoring and/or diagnostic tool for Fabry disease.

A cost-benefit analysis on tandem mass spectrometry of inherited metabolic diseases in Korea

PURPOSE: Tandem mass spectrometry (MS/MS) is effective screening test for inherited metabolic diseases. In this study, we estimate potential costs and benefits of using tandem mass spectrometry (MS/MS) to screen newborns for inherited metabolic diseases (phenylketonuria, BH4 deficiency, citrullinemia, maple syrup urine disease, propionic aciduria, isovaleric aciduria, glutaric aciduria type 1, LCHAD deficiency) in Korea. METHODS: From April 2001 to March 2004, 79,179 newborns were screened for amino acid disorders, organic acid disorders, and fatty acid oxidative disorders. Twenty-eight newborns were diagnosed with one of the metabolic disorder and the collective estimated prevalence amounted to 1 in 2,800 with a sensitivity of 97.67%, a specificity of 99.28%, a recall rate of 0.05%, and a positive preditive value of 6.38%. We calculated and compared the total costs in case when neonatal screening on phenylketonuria, BH4 deficiency, citrullinemia, maple syrup urine disease, propionic aciduria, isovaleric aciduria, glutaric aciduria type 1, LCHAD deficiency is implemented, and when not. RESULTS: If the neonatal screening on phenylketonuria, BH4 deficiency, citrullinemia, maple syrup urine disease, propionic aciduria, isovaleric aciduria, glutaric aciduria type 1, LCHAD deficiency is implemented, total benefits far exceed costs at a ratio of 1.40:1. CONCLUSION: Although, this study only concerns the monetary aspects of the neonatal screening, tandem mass spcetrometry for neonatal screening is cost-effective compared with not screening. The study appears to support the introduction of tandem mass spectrometry into a Korea neonatal screening programme for inherited metabolic diseases.

Fatty acid oxidation disorders / 한양의대학술지

Inborn errors of fatty acid mitochondrial oxidation (FAOD) have drawn considerable attention in recent years because of rapid pace of discovery of new defects and an ever-increasing spectrum of clinical phenotypes. This review describes a clinical and biochemical phenotypes, diagnosis and treatment of FAOD. Some of FAOD can not be detected by conventional biochemical investigations, even when a patient is symptomatic with fasting intolerance or functional failure of fatty acid dependent tissue (s). Diagnosis must ultimately be based on direct assay of the involved enzyme, however, preliminary indicators may come from determination of carnitine and intermediate metabolites in plasma, profiling of urine organic acid, and radioisotopic screening assays with lymphocytes or cultured fibroblasts. We are faced with the following major challenges: whether to include FAOD in newborn screening programs, the investigation of the rules played by individual disorders in maternal complication during pregnancy, sudden and unexpected death in early life, and pediatric acute/fulminant liver failure.

A Case of 2-Methylbutyryl-CoA Dehydrogenase Deficiency / 소아과

We report a one-day-old Korean boy with 2-Methylbutyryl-CoA dehydrogenase(2-MBCDase) deficiency detected by urine organic acid and acylglycine analysis, plasma acylcarnitine analysis and confirmed by enzyme assay and Western blot. The patient was born at 35 weeks and three days with oligohydroamnios and premature rupture of membrane for 31 hours, as a second child of healthy non-consanguineous parents. There was no significant family history and spontaneous abortion. He was admitted at NICU under ventilator care due to prematurity, respiratory difficulty, and decreased generalized muscle tone. During the first week of hospitalization, he presented with disseminated intravascular coagulation and sepsis. A grade IV intraventricular hemorrhage on brain sonography was observed on the 7th day after birth with seizure. The clinical course of aggravation and recovery was repeated for one month. In laboratory tests, blood C5-acylcarnitines(isovaleryl/ methylbutyrylcarnitine) and urine 2-methylbutyrylglycine(2-MBG) were markedly elevated; butyrylglycine and isobutyrylglycine were also detected in small amounts in the urine. SBCAD(short branched-chain acyl-CoA dehydrogenase) enzyme activity was undetectable in cultured skin fibroblasts and Western blot showed no detectable immuno-reactive protein. Molecular analysis of the 2-MBCD gene revealed a polymorphism in the leader peptide region(38G>A; Arg13Lys) and homozygous for a non-coding polymorphism 639T>C. This is the first such case in Korea. This disorder is known to be relatively common in one other oriental ethnic group, the Hmong. The baby has been fed on a maple syrup urine disease(MSUD)-similar diet program, and is still alive and is 26-months-old now. However, he developed significant neurologic complications including communicating hydrocephalus, cerebral palsy, and blindness. Presumably the prematurity and its complications may also attribute to his severe neurologic problems. However, the clinical course was particularly severe, a finding in contrast with the observation from several asymptomatic Hmong cases. The clinical course of 2-MBCDase deficiency could be very variable and careful monitoring and follow up should be considered.

The effectiveness of Lysophosphatic acid (LPA) as a biological marker in gynecologic cancer patients / 대한산부인과학회잡지

OBJECTIVE: LPAs are suggested as useful biological markers in early detection of ovarian carcinoma and other gynecological malignancies except breast and hematologic malignancy. We assessed the possible diagnostic role of serum LPA level in cervical, ovarian and the uterine corpus in Korean women. METHODS: The patients were enrolled in Hanyang University Hospital, Department of OB/GYN from Jan. 1999 to Jun. 2001. There were 19 ovarian carcinomas including 2 metastatic carcinomas, and 1 primary peritoneal carcinoma, 10 cervical carcinomas, 6 uterine carcinomas, 15 benign tumor as the study group and 5 healthy nulliparous women as the control group. Plasma was obtained following the centrifuge of whole blood, LPA was extracted from the plasma and the level was assessed by tandem mass spectrometry in multiple reaction mode. The quantity was measured by ratio of level of LPA and standard material, C14:0 LPA, in chromatogram compared with standard. The level of LPA were compared among control group, benign disease and gynecological malignancies, and also with conventional tumor markers. The statistical significance was analyzed by unpaired student-T test and McNemar test. RESULTS: The mean level of LPA and standard deviation were 7.1698 nmol/mL, 1.70 in malignancies, 4.5357 nmol/mL, 1.10 in benign disease and 5.2812 nmol/mL, 0.88 in healthy control. The level of LPA was significantly higher than in benign and control groups (p0.05). But, in cervical cancer, LPA level is more sensitive than CEA (p=0.039). CONCLUSION: The levels of LPA in cervical cancer, uterine cancer, ovarian carcinoma were significantly higher than in benign disease. Thus LPA is considered as an useful tumor marker in diagnosis and follow-up after treatment, especially in recurrent cervical carcinoma and uterine carcinoma which have no sensitive tumor markers. But further study with large number of casesfor a long period is required for clinical application in the future.

A Case of Glutaric Aciduria Type I with Macrocephaly

Glutaric aciduria type 1(GA1) is an autosomal recessive disorder of the lysine, hydroxylysine and tryptophan metabolism caused by the deficiency of mitochondrial glutaryl-CoA dehydrogenase. This disease is characterized by macrocephaly at birth or shortly after birth and various neurologic symptoms. Between the first weeks and the 4-5th year of life, intercurrent illness such as viral infections, gastroenteritis, or even routine immunizations can trigger acute encephalopathy, causing injury to caudate nucleus and putamen. But intellectual functions are well preserved until late in the disease course. We report a one-month-old male infant with macrocephaly and hypotonia. In brain MRI, there was frontotemporal atrophy(widening of sylvian cistern). In metabolic investigation, there were high glutarylcarnitine level in tandem mass spectrometry and high glutarate in urine organic acid analysis, GA1 was confirmed by absent glutaryl-CoA dehydrogenase activity in fibroblast culture. He was managed with lysine free milk and carnitine and riboflavin. He developed well without a metabolic crisis. If there is macrocephaly in an infant with neuroradiologic sign of frontotemporal atrophy, GA1 should have a high priority in the differential diagnosis. Because current therapy can prevent brain degeneration in more than 90% of affected infants who are treated prospectively, recognition of this disorder before the brain has been injured is essential for treatment.

A Case of Krabbe Disease with Infantile Spasm

Krabbe disease is a rare autosomal recessive disorder clinically characterized by retardation in motor development, prominent spasticity, seizures, and optic atrophy. Pathologically, there are many globoid cells in the white matter, in addition to the lack of myelin and the presence of severe gliosis. Hence Krabbe disease is known as globoid cell leukodystrophy. Biochemically, the primary enzymatic deficiency in Krabbe disease is galactocerebroside beta-galactosidase. Patients with Krabbe disease can be subdivided into the early-onset type and late-onset type, according to the onset of clinical manifestations. Most patients with early-onset type die before their second birthday. We describe a girl with Krabbe disease associated with uncontrolled seizures, which was confirmed with biochemical study and MRI. The clinical findings of this patient included hyperirritability, scissoring of the legs, flexion of arm, and clenching of the fists, and generalized tonic seizures. EEG showed hypsarrhythmia, and MRI demonstrated degenerative white matter changes in bilateral periventricular white matter, posterior rim of internal capsule, basal ganglia and brain stem on T2W1 and FLAIR image. The diagnosis was based on clinical features of progressive neurologic deterioration in conjunction with low galactocerebroside beta-galactosidase activity.

A Case of Rhizomelic Chondrodysplasia Punctata Type I

Rhizomelic chondrodysplasia punctata(RCDP) is a rare autosomal recessive disorder clinically characterized by symmetrical shortening of the proximal limbs, contractures of joints, a typical dysmorphic face, cataracts, and itchyosis. Patients with RCDP can be subdivided into three subgroups based on biochemical analysis and complementation studies. RCDP type I results from mutations in the PEX7 gene encoding the peroxisomal targeting signal type II(PST2) receptors and presents with both a defect in plasmalogen biosynthesis and phytanic acid oxidation. RCDP type II is deficient in the activity of dihydroxyacetonephosphate acyltransferase(DHAP-AT). RCDP type III is deficient in alkyl-dihydroxyacetonephosphate synthase(alkyl-DHAP). We report a case of RCDP type I which was confirmed with biochemical study, fibroblast culture, and gene study.

Serum Lipid Levels and Fatty Acid Metabolism in the Rat With Adriamycin Induced Cardiomyopathy

PURPOSE: Adriarnycin induced cardiomyopathy is irreversible and may procede to clinical congestive heart failure. Recently, it has been suggested that adriamycin may exert cardiomyopathy due to inhibition of transport across mitochondrial membranes rnediated by the carnitine palmitoyltransferase system(CPT I). The effect of adriamycin on fatty acid metabolisrn according to cumulative dose was not clarified. The purpose of this study was to ascertain the acute effect of adriamycin on lipid and fatty acid metabolism accoring to cumulative dose. METHODS: Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injection with adriamycin(5mg/kg) twice a week for 2 weeks. Serum lipid (total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol) and fatty acid levels were analyzed on the first day, 8th day, and 11th day after injection of adriamycin. RESULTS: Total cholesterol, triglyceride, and LDL cholesterol were significantly higher in adriamycin group compared to the control group. HDL cholesterol was similar in both groups. Total cholesterol and LDL choleterol level significantly increased over the adriamycin dose. Total fatty acid levels were significantly higher after injection of adriamycin. Long chain fatty acids such as palmitic acid, linoleic acicl and oleic acid levels were significantly elevated in the adriamycin group. CONCLUSION: Serum lipid and fatty acid levels increased significantly after injection of adriamycin.

Plugging the Biopsy Tract in Rabbit Liver: Gelfoam, Fibrin Sealant and NBCA

PURPOSE: To evaluate the effect of plugging the biopsy tract in rabbit liver and the pathologic changes caused by plugging materials. MATERIALS AND METHODS: Thirty-two New Zealand White rabbits were divided into four groups(eight rabbits in each) and compared with one another. They were labeled group A(control), B(gelfoam),C(fibrin sealant) or D(NBCA). The liver was exposed and biopsied with an 18G disposible biopsy gun. The inner Tru-cut needle was withdrawn and plugging was undertaken through the outer cannula of the biopsy gun. Bleeding times of each material were compared. The rabbits were sacrificed and pathologically evaluated for 17 days. RESULTS: Mean bleeding times were 46.7+/-34.5 sec in group A, 42.9+/-54.7 sec in group B, 12.6+/-15.0 sec in group C, and 0 sec in group D. In groups C and D, these results were statistically significant(p<0.01). Pathologically, fibrin sealant was lowest in foreign body reaction and fibrosis. NBCA was effective for the prevention of hemorrhage. CONCLUSION: NBCA and fibrin sealant effectively plug the biopsy tract through the outer cannula of an18 G biopsy gun.