Mucopolysaccharidosis (MPS) is an inherited metabolic disorder caused by a deficiency in enzymes that participate in the degradation of glycosaminoglycans (GAGs) such as heparin sulfate and dermatan sulfate. Left untreated, patients show progressive mental and physical deterioration due to deposition of GAGs in organs. Death often occurs due to cardiac or respiratory failure before patients reach their early twenties. MPS has several oral and dental manifestations. An enlarged head, short neck, and open mouth associated with a large tongue are major characteristics of MPS patients. Dental complications can be severe, including unerupted dentition, dentigerous cyst-like follicles, malocclusions, condylar defects, and gingival hyperplasia. A 21-year-old female patient with MPS was described in this article, with special emphasis on oral manifestations and dental treatment.
Dental Pulp Cavity ; Dentition ; Dermatan Sulfate ; Female ; Gingival Hyperplasia ; Glycosaminoglycans ; Head ; Heparin ; Humans ; Malocclusion ; Mouth ; Mucopolysaccharidoses ; Neck ; Oral Manifestations ; Respiratory Insufficiency ; Root Canal Therapy ; Tongue ; Young Adult

Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive lysosomal storage disease caused by mutation of the iduronate-2-sulfatase gene. The mutation results in iduronate-2-sulfatase deficiency, which causes the progressive accumulation of heparan sulfate and dermatan sulfate in cellular lysosomes. The phenotype, age of onset, and symptoms of MPS II vary; accordingly, the disease can be classified into either the early-onset type or the late-onset type, depending on the age of onset and the severity of the symptoms. In patients with severe MPS II, symptoms typically first appear between 2 and 5 years of age. Patients with severe MPS II usually die in the second decade of life although some patients with less severe disease have survived into their fifth or sixth decade. Here, we report the establishment of a preimplantation genetic diagnosis (PGD) strategy using multiplex nested polymerase chain reaction, direct sequencing, and linkage analysis. Unaffected embryos were selected via the diagnosis of a single blastomere, and a healthy boy was delivered by a female carrier of MPS II. This is the first successful application of PGD in a patient with MPS II in Korea
Age of Onset ; Blastomeres ; Dermatan Sulfate ; Diagnosis ; Embryonic Structures ; Female ; Heparitin Sulfate ; Humans ; Korea ; Lysosomal Storage Diseases ; Lysosomes ; Male ; Mucopolysaccharidoses ; Mucopolysaccharidosis II ; Multiplex Polymerase Chain Reaction ; Parturition ; Phenotype ; Polymerase Chain Reaction ; Preimplantation Diagnosis ; Prostaglandins D

BACKGROUND AND PURPOSE: Understanding the mechanisms underlying stroke can aid the development of therapies and improve the final outcome. The purposes of this study were to establish whether there are characteristic mechanistic differences in the frequency, severity, functional outcome, and mortality between left- and right-hemisphere ischemic stroke and, given the velocity differences in the carotid circulation and direct branching of the left common carotid artery from the aorta, whether large-vessel ischemia (including cardioembolism) is more common in the territory of the left middle cerebral artery. METHODS: Trial cohorts were combined into a data set of 476 samples. Using Trial of Org 10172 in Acute Stroke Treatment criteria, ischemic strokes in a total 317 patients were included in the analysis. Hemorrhagic stroke, stroke of undetermined etiology, cryptogenic stroke, and bilateral ischemic strokes were excluded. Laterality and vascular distribution were correlated with outcomes using a logistic regression model. The etiologies of the large-vessel strokes were atherosclerosis and cardioembolism. RESULTS: The overall event frequency, mortality, National Institutes of Health Stroke Scale (NIHSS) score, Glasgow Coma Scale score, and rate of mechanical thrombectomy interventions differed significantly between the hemispheres. Left-hemispheric strokes (54%) were more common than right-hemispheric strokes (46%; p=0.0073), and had higher admission NIHSS scores (p=0.011), increased mortality (p=0.0339), and higher endovascular intervention rates (p< or =0.0001). ischemic strokes were more frequent in the distribution of the left middle cerebral artery (122 vs. 97; p=0.0003) due to the higher incidence of large-vessel ischemic stroke in this area (p=0.0011). CONCLUSIONS: Left-hemispheric ischemic strokes appear to be more frequent and often have a worse outcome than their right-hemispheric counterparts. The incidence of large-vessel ischemic strokes is higher in the left middle cerebral artery distribution, contributing to these hemispheric differences. The hemispheric differences exhibit a nonsignificant trend when strokes in the middle cerebral artery distribution are excluded from the analysis.
Aorta ; Atherosclerosis ; Carotid Artery, Common ; Chondroitin Sulfates ; Cohort Studies ; Dermatan Sulfate ; Glasgow Coma Scale ; Heparitin Sulfate ; Humans ; Incidence ; Ischemia ; Logistic Models ; Middle Cerebral Artery ; National Institutes of Health (U.S.) ; Stroke ; Thrombectomy

BACKGROUND AND PURPOSE: Atherothrombotic cerebral infarction [atherothrombotic stroke (ATS)] shares common risk factors and pathophysiological mechanisms with coronary artery disease (CAD), and both diseases appear to have common susceptibility loci. The muscle RAS oncogene homolog gene (MRAS) has been identified as a susceptibility locus for CAD and is implicated in atherosclerosis. The aim of this study was to elucidate whether the single-nucleotide polymorphisms (SNPs) and haplotypes of MRAS are associated with increased risk of ATS in a population of Han Chinese. METHODS: A case-controlled association study was conducted in which only patients with ATS (identified as a major subtype in the Korean modification of the Trial of Org 10172 in Acute Stroke Treatment classification) were enrolled. Subgroup analyses were carried out to determine whether the effect of the MRAS polymorphism was specific to age and gender among the subjects. RESULTS: In total, 194 ATS and 186 control subjects were included in the present study. Two tagging SNPs were identified in MRAS (rs40593 and rs3755751). A multivariate regression analysis revealed a positive association between rs40593 and ATS under dominant and additive models after adjustment for covariates. Subgroup analyses revealed that there were no gender differences with respect to allele or genotype frequencies between the groups. The AG genotype for rs40593 (p=0.028), the CT genotype for rs3755751 (p=0.036), and G-allele carriers (AG plus GG) for rs40593 (p=0.015) exhibited a significant protective effect among those aged > or =45 years. For the haplotype analysis, ATS subjects aged > or =45 years had a higher frequency of the ACAC haplotype (76.0%) than the controls (68.1%; p<0.05); that haplotype was associated with an increased risk of ATS. CONCLUSIONS: The obtained data suggest a positive association between MRAS and ATS among the Han Chinese. Further studies should be performed with larger sample and among different ethnic populations, and gene-gene or gene-environment interactions should be considered.
Alleles ; Asian Continental Ancestry Group* ; Atherosclerosis ; Case-Control Studies ; Cerebral Infarction ; Chondroitin Sulfates ; Coronary Artery Disease ; Dermatan Sulfate ; Gene-Environment Interaction ; Genes, ras ; Genetic Variation* ; Genotype ; Haplotypes ; Heparitin Sulfate ; Humans ; Muscles ; Polymorphism, Single Nucleotide ; Risk Factors ; Stroke*

BACKGROUND: Impaired renal function may contribute to development of stroke and small vessel pathology in the brain. We investigated whether stroke subtype, initial stroke severity, early neurologic outcomes, time to cerebral infarction occurrence, and the presence of small vessel pathology in the brain are different between patients with end stage renal disease (ESRD) and those with renal transplantation (RT). METHODS: A total of 57 consecutive de novo RT patients (RT group) and 120 patients undergoing dialysis due to ESRD (ESRD group) who developed a first-ever acute cerebral infarction were enrolled. We compared stroke subtypes based on the Trial of Org 10172 in Acute Stroke Treatment classification, the presence of small vessel pathology (cerebral microbleed, leukoaraiosis and silent lacunar infarction) on MRI, stroke severity based on the National Institutes of Health Stroke Scale (NIHSS) and in-hospital mortality between the groups. RESULTS: The stroke subtypes, NIHSS scores at admission and in-hospital mortality were not different between the two groups. On multivariate analysis, the presence of high grade periventricular white matter changes tended to be more frequently detected in the ESRD group than the RT (P=0.078). The time from starting dialysis to stroke was longer in the RT group (129.9+/-60.9 months) than in the ESRD group (51.1+/-46.1 months). CONCLUSIONS: The stroke patterns, severity and short term outcomes were not different between RT and ESRD. The risk of cerebral infarction and high grade periventricular white matter changes may be reduced after RT in patients with ESRD.
Brain ; Cerebral Infarction ; Chondroitin Sulfates ; Dermatan Sulfate ; Dialysis ; Glycosaminoglycans ; Heparitin Sulfate ; Hospital Mortality ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Leukoaraiosis ; Multivariate Analysis ; National Institutes of Health (U.S.) ; Stroke

Sulodexide is composed of two glycosaminoglycans (fast-moving heparin 80%, dermatan sulfate 20%) that are capable of preventing diabetic nephropathy by correcting abnormal glycosaminoglycan metabolism. Considering heparin-like propertyof sulodexide, side effect profiles of sulodexide are expected to be similar with those of heparin. Among those side effects, we remarked on heparin-induced hyperkalemia and hereby report a case of severe hyperkalemia during the use of sulodexide. A 52-year-old man with diabetic nephroapthy and hypertension was admitted to our hospital because of severe hyperkalemia up to 7.5 meq/L. His clinical condition was stable and medications including losartan and furosemide had not been changed for last 6 months except the addition of sulodexide, which was started 30 days prior to admission. Despite intensive use of Kayexalate and immediate discontinuation of losartan, hyperkalemia aggravated up to 8.0 meq/L. After recognition of possible sulodexide-induced hyperkalemia, sulodexide was discontinued, which resulted in rapid correction of hyperkalemia. In view of the above discussed clinical consideration, we suspect sulodexide as a major cause of hyperkalmia and report this case with a review of literature.
Dermatan Sulfate ; Diabetic Nephropathies ; Furosemide ; Glycosaminoglycans ; Heparin ; Humans ; Hyperkalemia ; Hypertension ; Losartan ; Middle Aged ; Polystyrenes

OBJECTIVE: We evaluated whether serum total bilirubin levels were related to large artery atherosclerosis (LAA), classified by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and stroke severity at admission in acute ischemic stroke. METHODS: We analyzed clinical features, laboratory tests, and radiologic findings such as brain MRI and MR angiography of patients admitted to our hospital within 24 hours of the onset of ischemic stroke between January 2004 and June 2007. By TOAST classification, 237 patients [115 with LAA and 122 with small artery occlusion (SAO)] were selected. We divided serum total bilirubin levels into three groups: Low (<0.6 mg/dL), Middle (0.6~0.9 mg/dL), and High (1.0~1.2 mg/dL). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) at admission. We divided NIHSS scores into three groups: Mild (0-6), Moderate (7-15), and Severe group (>15). RESULTS: Total bilirubin levels were significantly higher in the Mild group than other groups, and high-sensitivity C reactive protein (hsCRP) levels were significantly higher in the Severe group than other groups in LAA. There were no differences for these factors in SAO. We found a significant correlation between total bilirubin levels and stroke severity in LAA (p=0.005). CONCLUSION: Higher serum total bilirubin levels were associated with lower stroke severity at admission in LAA but not SAO.
Angiography ; Arteries ; Atherosclerosis ; Bilirubin ; Brain ; C-Reactive Protein ; Chondroitin Sulfates ; Dermatan Sulfate ; Heparitin Sulfate ; Humans ; National Institutes of Health (U.S.) ; Stroke

We report a case of Hunter syndrome in a 4 year old boy, who presented with firm skin colored papules and nodules that coalesce to form a reticular pattern (pebbling of the skin) with extensive Mongolian spots. The lesions are arranged bilaterally and symmetrically over the scapulae, upper arm and lateral aspects of the thighs. He also has low intelligence, coarse face, saddle nose and claw hand contracture of both hands. The result of qualitative analysis of urine was positive for dermatan sulfate and heparan sulfate. And enzyme activity of iduronate-2-sulfatase is decreased in plasma and leukocyte. A skin biopsy specimen section stained with hematoxylin-eosin showed widely separated collagen bundles in the dermis associated with mucin deposition.
Animals ; Arm ; Biopsy ; Collagen ; Contracture ; Dermatan Sulfate ; Dermis ; Hand ; Heparitin Sulfate ; Hoof and Claw ; Intelligence ; Leukocytes ; Mongolian Spot ; Mucins ; Mucopolysaccharidosis II ; Nose ; Plasma ; Scapula ; Skin ; Thigh

BACKGROUND: Although levels of D-dimer and fibrinogen/fibrin degradation products (FDP) are low in the circulation of healthy individuals, their levels are significantly elevated in patients with thromboembolic diseases. The aim of this study was to investigate the clinical utilities of D-dimer and FDP in the early diagnosis of stroke subtypes and the prediction of early prognosis. METHODS: Hospitalized patients due to acute ischemic stroke underwent measurement of plasma levels of D-dimer and FDP within 12 hours after admission. Stroke severity was assessed on admission and 2 weeks later using the National Institutes of Health Stroke Scale (NIHSS). Stroke subtypes were classified according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment criterion. RESULTS: D-dimer and FDP levels were significantly higher in the cardioembolic group than in the atherosclerotic and lacunar groups. There was independent correlation between the level of FDP and cardioembolism. Ninety-six patients showed clinical improvement that was defined by a reduction of more than 4 points on the NIHSS two weeks later compared with that on admission. The level of D-dimer was higher in patients with clinical improvement than in patients without improvement (p=0.032). However, there was no correlation between the level of D-dimer and early improvement. CONCLUSIONS: These results show that measurement of FDP in acute ischemic stroke could be helpful in subtype classification. However, D-dimer and FDP were not related with early prognosis.
Cerebral Infarction ; Chondroitin Sulfates ; Dermatan Sulfate ; Early Diagnosis ; Fibrin Fibrinogen Degradation Products ; Formycins ; Heparitin Sulfate ; Humans ; National Institutes of Health (U.S.) ; Plasma ; Ribonucleotides ; Stroke ; Thromboembolism

OBJECTIVE: To investigate the correlation between the pulse pressure (PP) and functional outcome in acute middle cerebral arterial (MCA) ischemic stroke. METHOD: We reviewed the medical records of 52 first-ever hemiplegic MCA ischemic stroke patients (age 61.5+/-9.7 years; 35 men, 17 women). Functional outcomes were evaluated with Korean-modified Barthel index (K-MBI), functional independence measure (FIM), Korean-national institutes of health stroke scale (K-NIHSS), and Korean-mini mental state examination (K-MMSE) on 3 days and 3 months after the onset of stroke in all the subjects. The PP was measured six times within initial 24 hours after stroke onset and then the highest PP was selected for the analysis. RESULTS: The degree of PP elevation revealed the significant correlations with male gender, over the age of 55 years, diabetes mellitus, and current smoking history, respectively (p<0.05). In TOAST (Trial Org 10172 in Acute Stroke Treatment) classification, the large artery atherosclerosis group showed significantly the higher PP rather than the other groups (p<0.05). There were inverse correlations between the PP and each of FIM and K-MBI scores on 3 months after stroke onset (p=0.000, 0.009; r=- 0.479, -0.358). There was an inverse correlation between the PP and the change of FIM (p=0.000, r=-0.532). CONCLUSION: The PP within initial 24 hours after stroke onset revealed significant correlation with functional outcome. The management for the proper PP gives the favorable effect on the functional outcome in acute MCA territory ischemic stroke.
Academies and Institutes ; Arteries ; Atherosclerosis ; Blood Pressure ; Chondroitin Sulfates ; Dermatan Sulfate ; Diabetes Mellitus ; Hemiplegia ; Heparitin Sulfate ; Humans ; Male ; Medical Records ; Middle Cerebral Artery ; Smoke ; Smoking ; Stroke