DOCSLIB.ORG

Anesthetic Considerations and Clinical Manifestations 243

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Anesthetic Considerations and Clinical Manifestations 243 MUCOPOLYSACCHARIDOSES: ANESTHETIC CONSIDERATIONS AND CLINICAL MANIFESTATIONS 243 MUCOPOLYSACCHARIDOSES: ANESTHETIC CONSIDERATIONS AND CLINICAL MANIFESTATIONS * ** *** JERMALE A. SAM , AMIR R. BALUCH , RASHID S. NIAZ , *** **** LINDSEY LONADIER AND ALAN D. KAYE Abstract Mucopolysaccharidosis (MPS) is a group of genetic disorders that presents challenges during anesthetic care and in particular difficulty with airway management. Patients should be managed by experienced anesthesiologists at centers that are familiar with these types of conditions. Rarely encountered disease states have been identified as important topics in the continuing education of clinical anesthesiologists. This review will define MPS, describe the pathophysiology of MPS, describe how patients with this rare lysosomal storage disorders have dysfunction of tissues, cite the incidence of MPS, list the clinical manifestations and specific problems associated with the administration of anesthesia to patients with MPS, present treatment options for patients with MPS, define appropriate preoperative evaluation and perioperative management of these patients, including, to anticipate potential postoperative airway problems. Introduction Mucopolysaccharidoses (MPS) are a group of rare genetic lysosomal storage disorders characterized by the deficiency in or complete lack of necessary lysosomal enzymes required for the stepwise breakdown of glycosaminoglycans (GAGs, also known as mucopolysaccharidoses)1-5. Consequently, fragments of GAGs accumulate intracellularly in the lysosome resulting in cellular enlargement causing disruption/dysfunction of structure and function of tissues. This process leads to numerous clinical abnormalities. Incidence of all types of MPS is reported to be between 1in 10,000 to 1 in 30,000 live births and are transmitted autosomal recessive except for MPS II which is X-linked1,4,5. Pathophysiology Glycosaminoglycans are long-chain complex carbohydrates consisting of repeating sulfated acidic and amino sugar disaccharide units. They are usually linked to proteins to form proteoglycans, which are the major * Resident, Department of Surgery, Riverside Methodist Hospital, Columbus, Ohio. ** Attending Staff Physician, Metropolitan Anesthesia Consultants, Dallas, Texas. *** Research Associate, Louisiana State University Health Science Center, New Orleans, Louisiana. **** Professor and Chairman, Department of Anesthesiology, Louisiana State University Health Science Center, New Orleans, Louisiana. Address Correspondence to: Alan D Kaye, MD, PhD, Professor and Chairman, Department of Anesthesiology, Louisiana State University School of Medicine, 1542 Tulane Ave, Room 656, New Orleans, LA 70112. Tel: (504) 568-2319, Fax: (504) 568-2317, E-mail: [email protected] 243 M.E.J. ANESTH 21 (2), 2011 244 JERMALE A SAM constituents of the ground substance of connective tissue, lubricant in joint fluid, and the surface coating that initially binds growth factors to cells. The major GAGs are chondroitin-4-sulfate, chondroitin-6-sulfate, heparan sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. In the organism, these substances are degraded by the sequential action of lysosomal enzymes leading to a stepwise shortening of the terminal sulfate, acidic, and amino sugar residues. Deficient/dysfunctional activity of the degradative enzymes results in MPS disorder of which there are eleven types based on levels of severity. The clinical phenotype of the disorder depends upon the distribution and turnover of the substrate affected by the deficiency, rather than the distribution of the enzyme1-6. Classification Of the 11 total MPS disorders, there are 7 major types classified I through IX. MPS V, formerly Scheie syndrome, and MPS VIII are no longer recognized4. The MPS disorders are differentiated by clinical features and age at presentation and biochemically by the associated enzyme deficiency. As a general rule, the impaired degradation of heparan sulfate is more closely associated with mental deficiency, and the impaired degradation of dermatan, chondroitin and keratan sulfate results in mesenchymal abnormalities6,7. Overall, these disorders can be grouped into four broad categories according to their dominant clinical features: 1. Soft tissue storage and skeletal disease with or without brain disease (MPS I, II,VII). 2. Soft tissue and skeletal disease (MPS VI). 3. Primarily skeletal disease (MPS IVa, IVb). 4. Primarily CNS disease (MPS IIIa-d). Table 1 Specific classifications and features of MPS Number Eponym Enzyme GAG stored Craniofacial Joint and skeletal Cardiac Visceral, visual, deficiency abnormalities deformities involvement and neurologic manifesations MPS I (severe) Hurler syndrome -L-iduronidase dermatan sulfate, macrocephaly stiff joints, coronary intimal hepato- heparan sulfate coarse facies thoracolumbar and valvular splenomegaly; macroglossia kyphosis, possible thickening, umbilical and hydrocephalus odontoid deformity, mitral inguinal hernias; hypoplasia, short regurgitation, corneal clouding; neck, cardiomegaly severe mental short stature retardation MPS I Scheie syndrome -L- iduronidase dermatan sulfate, coarse facies, short neck, normal aortic hepato- (attenuated) heparan sulfate macroglossia stature regurgitation splenomegaly; prognathia umbilical and inguinal hernias; corneal clouding 244 MUCOPOLYSACCHARIDOSES: ANESTHETIC CONSIDERATIONS AND CLINICAL MANIFESTATIONS 245 MPS I (attenuated Hurler-Scheie - L iduronidase dermatan sulfate, macrocephaly, diffuse joint mitral and aortic Hepato- with different syndrome heparan sulfate coarse facies, limitation, value thickening splenomegaly, features) macroglossia, short neck, and regurgitation umbilical and micrognathia short stature inguinal hernias, corneal clouding MPS II (severe) Hunter syndrome Iduronate sulfatase dermatan sulfate, Macrocephaly, diffuse joint coronary intimal hepato - (severe) heparan sulfate coarse facies, limitation, short thickening, splenomegaly, hydrocephalus neck, short stature ischemic no corneal cardiomyopathy clouding MPS Hunter iduronate sulfatase dermatan sulfate, II(attenuated) syndrome(mild) heparan sulfate MPS IIIA Sanfilippo A Heparan N heparan sulfate coarse facies, mild stiff joints, minimal to none severe retardation, (symptoms appear syndrome sulfatase heavy eyebrows short stature, behavioral after the first year that meet in dysphagia problems, diarrhea of life) center of face above the nose MPS IIIB Sanfilippo B N acetyl heparan sulfate coarse facies mild stiff joints, minimal to none developmental syndrome glucosaminidase short stature, delay, walking problems, behavioral lumbar vertebral problems issues, dysphagia MPS IIIC Sanfilippo C acetyl Co heparan sulfate coarse facies mild stiff joints, minimal to none developmental syndrome glucosaminide short stature, delay, acetlytransferase lumbar vertebral behavioral issues, dysphagia problems MPS IIID Sanfilippo D N heparan sulfate coarse facies mild stiff joints, minimal to none developmental syndrome acetylglucosamine short stature, delay, 6 sulfatase lumbar vertebral behavioral issues, dysphagia problems MPS IVA Morquio galactose 6 keratan sulfate, coarse facies joint laxity, aortic mild corneal syndrome, type A sulfatase chondroitin-6- severe kypho-regurgitation opacities, hepato- sulfate scoliosis, odontoid splenomegaly hypoplasia, short neck, C1-C2, C2- C3 subluxation, short stature MPS IVB Morquio beta galactosidase Keratan sulfate, coarse facies joint laxity, aortic mild corneal syndrome, type B chondroitin-6- severe kypho- regurgitation opacities, hepato- sulfate scoliosis, odontoid splenomegaly hypoplasia, short neck, C1-C2, C2- C3 subluxation, short stature 245 M.E.J. ANESTH 21 (2), 2011 246 JERMALE A SAM MPS VI Maroteaux-Lamy N- dermatan sulfate, Macrocephaly, mild joint stiffness, mitral and aortic syndrome acetylgalactosamin heparan sulfate coarse facies, kyphoscoliosis, value thickening e-4-sulfatase macroglossia, odontoid and regurgitation hydrocephalus hypoplasia, short stature MPS VII Sly syndrome beta glucoronidase dermatan sulfate, Macrocephaly, joint flexion, mitral and aortic heparan sulfate, coarse facies contractures, value thickening chondroitin 4,6 thoracolumbar and regurgitation sulfate deformity, hip dysplasia, odontoid hypoplasia, short stature MPS IX Hyaluronidase Hyaluronan (Modified from Diaz JH, Belani KG. Perioperative management of children with mucopolysaccharidoses. Anesth Analg 1993; 77:1261-70). Clinical Manifestations As mentioned previously, MPS disorders are characterized by progressive craniofacial, joint, and skeletal deformities, progressive cardiac involvement, and early death from pulmonary infection or cardiac failure often before childhood1-18. Hurler syndrome is the prototypical MPS and occurs in 1 in 100,000 live births (Fig. 1)13,14. GAGs deposits lead to thickened heart valves, and valvular insufficiency more often than stenosis. Myocardial hypertrophy, ventricular dysfunction and cardiomyopathy result from accumulation of GAGs in the myocardium and frequently cause congestive heart failure and death. Intimal deposition of GAGs causes coronary luminal narrowing and occlusion that can be progressive1-16. GAGs are also deposited in abdominal viscera leading to hepatosplenomegaly (HSM) in most if not all patients. Umbilical and inguinal hernias can be due to abdominal protuberance from hepatospenomegaly. HSM and ineffective connective tissue support of the anterior abdominal wall often occurs. In addition to heart disease and HSM, most infants
Load more

Recommended publications
  • Epidemiology of Mucopolysaccharidoses Update
    diagnostics Review Epidemiology of Mucopolysaccharidoses Update Betul Celik 1,2 , Saori C. Tomatsu 2 , Shunji Tomatsu 1 and Shaukat A. Khan 1,* 1 Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; [email protected] (B.C.); [email protected] (S.T.) 2 Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; [email protected] * Correspondence: [email protected]; Tel.: +302-298-7335; Fax: +302-651-6888 Abstract: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a lysosomal enzyme deficiency or malfunction, which leads to the accumulation of glycosaminoglycans in tissues and organs. If not treated at an early stage, patients have various health problems, affecting their quality of life and life-span. Two therapeutic options for MPS are widely used in practice: enzyme replacement therapy and hematopoietic stem cell transplantation. However, early diagnosis of MPS is crucial, as treatment may be too late to reverse or ameliorate the disease progress. It has been noted that the prevalence of MPS and each subtype varies based on geographic regions and/or ethnic background. Each type of MPS is caused by a wide range of the mutational spectrum, mainly missense mutations. Some mutations were derived from the common founder effect. In the previous study, Khan et al. 2018 have reported the epidemiology of MPS from 22 countries and 16 regions. In this study, we aimed to update the prevalence of MPS across the world. We have collected and investigated 189 publications related to the prevalence of MPS via PubMed as of December 2020. In total, data from 33 countries and 23 regions were compiled and analyzed.
    [Show full text]
  • Long-Term Outcomes of Systemic Therapies for Hurler Syndrome: an International Multicenter Comparison
    © American College of Medical Genetics and Genomics ORIGINAL RESEARCH ARTICLE Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison Julie B. Eisengart, PhD1, Kyle D. Rudser, PhD2, Yong Xue, MD, PhD3, Paul Orchard, MD4, Weston Miller, MD4, Troy Lund, MD, PhD4, Ans Van der Ploeg, MD, PhD5, Jean Mercer, RGN, RSCN6, Simon Jones, MBChB7, Karl Eugen Mengel, MD8, Seyfullah Gökce, MD8, Nathalie Guffon, MD9, Roberto Giugliani, MD, PhD10, Carolina F.M. de Souza, MD, PhD10, Elsa G. Shapiro, PhD1,11 and Chester B. Whitley, PhD, MD12 Purpose: Early treatment is critical for mucopolysaccharidosis type I Results: Survival was worse when comparing ERT versus HCT, and (MPS I), justifying its incorporation into newborn screening. Enzyme Untreated versus ERT. The cumulative incidences of hydrocephalus replacement therapy (ERT) treats MPS I, yet presumptions that ERT – and cervical spinal cord compression were greater in ERT versus HCT. cannot penetrate the blood brain barrier (BBB) support recommen- Findings persisted in the sensitivity analysis. dations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics precludes rando- Conclusion: As newborn screening widens treatment opportunity for mized comparison of ERT with HCT, but insight into this comparison Hurler syndrome, this examination of early treatment quantifies some is presented with an international cohort of patients with Hurler ERT benefit, supports presumptions about BBB impenetrability, and syndrome who received long-term ERT from a young age. aligns with current guidelines to treat with HCT. Methods: Long-term survival and neurologic outcomes were Genet Med compared among three groups of patients with Hurler syndrome: 18 advance online publication 8 March 2018 treated with ERT monotherapy (ERT group), 54 who underwent HCT (HCT group), and 23 who received no therapy (Untreated).
    [Show full text]
  • Pathophysiology of Mucopolysaccharidosis
    Pathophysiology of Mucopolysaccharidosis Dr. Christina Lampe, MD The Center for Rare Diseases, Clinics for Pediatric and Adolescent Medicine Helios Dr. Horst Schmidt Kliniken, Wiesbaden, Germany Inborn Errors of Metabolism today - more than 500 diseases (~10 % of the known genetic diseases) 5000 genetic diseases - all areas of metabolism involved - vast majority are recessive conditions 500 metabolic disorders - individually rare or very rare - overall frequency around 1:800 50 LSD (similar to Down syndrome) LSDs: 1: 5.000 live births MPS: 1: 25.000 live births 7 MPS understanding of pathophysiology and early diagnosis leading to successful therapy for several conditions The Lysosomal Diseases (LSD) TAY SACHS DIS. 4% WOLMAN DIS. ASPARTYLGLUCOSAMINURIA SIALIC ACID DIS. SIALIDOSIS CYSTINOSIS 4% SANDHOFF DIS. 2% FABRY DIS. 7% POMPE 5% NIEMANN PICK C 4% GAUCHER DIS. 14% Mucopolysaccharidosis NIEMANN PICK A-B 3% MULTIPLE SULPH. DEF. Mucolipidosis MUCOLIPIDOSIS I-II 2% Sphingolipidosis MPSVII Oligosaccharidosis GM1 GANGLIOSIDOSIS 2% MPSVI Neuronale Ceroid Lipofuszinois KRABBE DIS. 5% MPSIVA others MPSIII D A-MANNOSIDOSIS MPSIII C MPSIIIB METACHROMATIC LEUKOD. 8% MPS 34% MPSIIIA MPSI MPSII Initial Description of MPS Charles Hunter, 1917: “A Rare Disease in Two Brothers” brothers: 10 and 8 years hearing loss dwarfism macrocephaly cardiomegaly umbilical hernia joint contractures skeletal dysplasia death at the age of 11 and 16 years Description of the MPS Types... M. Hunter - MPS II (1917) M. Hurler - MPS I (1919) M. Morquio - MPS IV (1929) M. Sanfilippo - MPS III (1963) M. Maroteaux-Lamy - MPS IV (1963) M. Sly - MPS VII (1969) M. Scheie - MPS I (MPS V) (1968) M. Natowicz - MPS IX (1996) The Lysosome Lysosomes are..
    [Show full text]
  • Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment
    International Journal of Molecular Sciences Review Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment Francesca D’Avanzo 1,2 , Laura Rigon 2,3 , Alessandra Zanetti 1,2 and Rosella Tomanin 1,2,* 1 Laboratory of Diagnosis and Therapy of Lysosomal Disorders, Department of Women’s and Children ‘s Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy; [email protected] (F.D.); [email protected] (A.Z.) 2 Fondazione Istituto di Ricerca Pediatrica “Città della Speranza”, Corso Stati Uniti 4, 35127 Padova, Italy; [email protected] 3 Molecular Developmental Biology, Life & Medical Science Institute (LIMES), University of Bonn, 53115 Bonn, Germany * Correspondence: [email protected] Received: 17 January 2020; Accepted: 11 February 2020; Published: 13 February 2020 Abstract: Mucopolysaccharidosis type II (MPS II, Hunter syndrome) was first described by Dr. Charles Hunter in 1917. Since then, about one hundred years have passed and Hunter syndrome, although at first neglected for a few decades and afterwards mistaken for a long time for the similar disorder Hurler syndrome, has been clearly distinguished as a specific disease since 1978, when the distinct genetic causes of the two disorders were finally identified. MPS II is a rare genetic disorder, recently described as presenting an incidence rate ranging from 0.38 to 1.09 per 100,000 live male births, and it is the only X-linked-inherited mucopolysaccharidosis. The complex disease is due to a deficit of the lysosomal hydrolase iduronate 2-sulphatase, which is a crucial enzyme in the stepwise degradation of heparan and dermatan sulphate.
    [Show full text]
  • Megalencephaly and Macrocephaly
    277 Megalencephaly and Macrocephaly KellenD.Winden,MD,PhD1 Christopher J. Yuskaitis, MD, PhD1 Annapurna Poduri, MD, MPH2 1 Department of Neurology, Boston Children’s Hospital, Boston, Address for correspondence Annapurna Poduri, Epilepsy Genetics Massachusetts Program, Division of Epilepsy and Clinical Electrophysiology, 2 Epilepsy Genetics Program, Division of Epilepsy and Clinical Department of Neurology, Fegan 9, Boston Children’s Hospital, 300 Electrophysiology, Department of Neurology, Boston Children’s Longwood Avenue, Boston, MA 02115 Hospital, Boston, Massachusetts (e-mail: [email protected]). Semin Neurol 2015;35:277–287. Abstract Megalencephaly is a developmental disorder characterized by brain overgrowth secondary to increased size and/or numbers of neurons and glia. These disorders can be divided into metabolic and developmental categories based on their molecular etiologies. Metabolic megalencephalies are mostly caused by genetic defects in cellular metabolism, whereas developmental megalencephalies have recently been shown to be caused by alterations in signaling pathways that regulate neuronal replication, growth, and migration. These disorders often lead to epilepsy, developmental disabilities, and Keywords behavioral problems; specific disorders have associations with overgrowth or abnor- ► megalencephaly malities in other tissues. The molecular underpinnings of many of these disorders are ► hemimegalencephaly now understood, providing insight into how dysregulation of critical pathways leads to ►
    [Show full text]
  • Tepzz¥5Z5 8 a T
    (19) TZZ¥Z___T (11) EP 3 505 181 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 03.07.2019 Bulletin 2019/27 A61K 38/46 (2006.01) C12N 9/16 (2006.01) (21) Application number: 18248241.4 (22) Date of filing: 28.12.2018 (84) Designated Contracting States: (72) Inventors: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB • DICKSON, Patricia GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Torrance, CA California 90502 (US) PL PT RO RS SE SI SK SM TR • CHOU, Tsui-Fen Designated Extension States: Torrance, CA California 90502 (US) BA ME • EKINS, Sean Designated Validation States: Brooklyn, NY New York 11215 (US) KH MA MD TN • KAN, Shih-Hsin Torrance, CA California 90502 (US) (30) Priority: 28.12.2017 US 201762611472 P • LE, Steven 05.04.2018 US 201815946505 Torrance, CA California 90502 (US) • MOEN, Derek R. (71) Applicants: Torrance, CA California 90502 (US) • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (74) Representative: J A Kemp Torrance, CA 90502 (US) 14 South Square • Phoenix Nest Inc. Gray’s Inn Brooklyn NY 11215 (US) London WC1R 5JJ (GB) (54) PREPARATION OF ENZYME REPLACEMENT THERAPY FOR MUCOPOLYSACCHARIDOSIS IIID (57) The present disclosure relates to compositions for use in a method of treating Sanfilippo syndrome (also known as Sanfilippo disease type D, Sanfilippo D, mu- copolysaccharidosis type IIID, MPS IIID). The method can entail injecting to the spinal fluid of a MPS IIID patient an effective amount of a composition comprising a re- combinant human acetylglucosamine-6-sulfatase (GNS) protein comprising the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1 and having the en- zymatic activity of the human GNS protein.
    [Show full text]
  • Diversity of Mutations and Distribution of Single Nucleotide Polymorphic Alleles in the Human -L-Iduronidase (IDUA) Gene
    article November/December 2002 ⅐ Vol. 4 ⅐ No. 6 Diversity of mutations and distribution of single nucleotide polymorphic alleles in the human ␣-L-iduronidase (IDUA) gene Peining Li, PhD1,3, Tim Wood, PhD1,4, and Jerry N. Thompson, PhD1,2 Purpose: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder resulting from a deficiency of the lysosomal glycosidase, ␣-L-iduronidase (IDUA). Patients with MPS I present with variable clinical manifestations ranging from severe to mild. To facilitate studies of phenotype-genotype correlation, the authors performed molecular studies to detect mutations in MPS I patients and characterize single nucleotide polymorphism (SNP) in the IDUA gene. Methods: Twenty-two unrelated MPS I patients were subjects for mutation detection using reverse transcriptional polymerase chain reaction (RT-PCR) and genomic PCR sequencing. Polymorphism analyses were performed on controls by restriction enzyme assays of PCR amplicons flanking nine IDUA intragenic single nucleotide polymorphic alleles. Results: Eleven different mutations including two common mutations (Q70X, W402X), five recurrent mutations (D315Y, P533R, R621X, R628X, S633L), and four novel mutations (R162I, G208D, 1352delG, 1952del25bp) were identified from MPS I patients. Multiple SNP alleles coexisting with the disease-causing mutations were detected. Allelic frequencies for nine SNP alleles including A8, A20, Q33H, L118, N181, A314, A361T, T388, and T410 were determined. Conclusions: The results provide further evidence for the mutational heterogeneity among MPS I patients and point out possible common haplotype structures in the IDUA gene. Genet Med 2002:4(6):420–426. Key Words: mucopolysaccharidosis type I, ␣-L-iduronidase (IDUA) gene, mutations, single nucleotide polymor- phism, haplotype Mucopolysaccharidosis type I (MPS I, MIM 252800) is an and results in lysosomal accumulation and excessive urinary autosomal recessive disorder caused by various lesions in the excretion of partially degraded dermatan sulfate and heparan ␣-L-iduronidase (IDUA) gene.
    [Show full text]
  • MECHANISMS in ENDOCRINOLOGY: Novel Genetic Causes of Short Stature
    J M Wit and others Genetics of short stature 174:4 R145–R173 Review MECHANISMS IN ENDOCRINOLOGY Novel genetic causes of short stature 1 1 2 2 Jan M Wit , Wilma Oostdijk , Monique Losekoot , Hermine A van Duyvenvoorde , Correspondence Claudia A L Ruivenkamp2 and Sarina G Kant2 should be addressed to J M Wit Departments of 1Paediatrics and 2Clinical Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Email The Netherlands [email protected] Abstract The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T3/T4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature.
    [Show full text]
  • Mucopolysaccharidosis Type I
    diagnostics Review Mucopolysaccharidosis Type I Francyne Kubaski 1,2,3,4 , Fabiano de Oliveira Poswar 1,2 , Kristiane Michelin-Tirelli 2,4 , Ursula da Silveira Matte 1,3,4,5,6, Dafne D. Horovitz 7, Anneliese Lopes Barth 7, Guilherme Baldo 1,3,4,5,8, Filippo Vairo 9,10 and Roberto Giugliani 1,2,3,4,5,6,11,* 1 Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre 91501970, Brazil; [email protected] (F.K.); [email protected] (F.d.O.P.); [email protected] (U.d.S.M.); [email protected] (G.B.) 2 Medical Genetics Service, HCPA, Porto Alegre 90035903, Brazil; [email protected] 3 INAGEMP, Porto Alegre 90035903, Brazil 4 Biodiscovery Research Group, Experimental Research Center, HCPA, Porto Alegre 90035903, Brazil 5 Gene Therapy Center, HCPA, Porto Alegre 90035903, Brazil 6 Department of Genetics, UFRGS, Porto Alegre 91501970, Brazil 7 Medical Genetics Department, National Institute of Women, Children, and Adolescent Health, Oswaldo Cruz Foundation, Rio de Janeiro 21040900, Brazil; [email protected] (D.D.H.); [email protected] (A.L.B.) 8 Department of Physiology, UFRGS, Porto Alegre 90050170, Brazil 9 Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; [email protected] 10 Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA 11 Postgraduation Program in Medicine, Clinical Sciences, UFRGS, Porto Alegre 90035003, Brazil * Correspondence: [email protected]; Tel.: +55-51-3359-6338; Fax: +55-51-3359-8010 Received: 31 January 2020; Accepted: 10 March 2020; Published: 16 March 2020 Abstract: Mucopolysaccharidosis type I (MPS I) is caused by the deficiency of α-l-iduronidase, leading to the storage of dermatan and heparan sulfate.
    [Show full text]
  • Sanfilippo Disease Type D: Deficiency of N-Acetylglucosamine-6- Sulfate Sulfatase Required for Heparan Sulfate Degradation
    Proc. Nat!. Acad. Sci. USA Vol. 77, No. 11, pp. 6822-6826, November 1980 Medical Sciences Sanfilippo disease type D: Deficiency of N-acetylglucosamine-6- sulfate sulfatase required for heparan sulfate degradation (mucopolysaccharidosis/keratan sulfate/lysosomes) HANS KRESSE, EDUARD PASCHKE, KURT VON FIGURA, WALTER GILBERG, AND WALBURGA FUCHS Institute of Physiological Chemistry, Waldeyerstrasse 15, D-4400 Mfinster, Federal Republic of Germany Communicated by Elizabeth F. Neufeld, July 10, 1980 ABSTRACT Skin fibroblasts from two patients who had lippo syndromes and excreted excessive amounts of heparan symptoms of the Sanfilippo syndrome (mucopolysaccharidosis sulfate and keratan sulfate in the urine. His fibroblasts were III) accumulated excessive amounts of hean sulfate and were unable to desulfate N-acetylglucosamine-6-sulfate and the unable to release sulfate from N-acety lucosamine)--sulfate linkages in heparan sulfate-derived oligosaccharides. Keratan corresponding sugar alcohol (17, 18). It was therefore suggested sulfate-derived oligosaccharides bearing the same residue at that N-acetylglucosamine-6-sulfate sulfatase is involved in the the nonreducing end and p-nitrophenyl6sulfo-2-acetamido- catabolism of both types of macromolecules. 2-deoxy-D-ucopyranoside were degraded normally. Kinetic In this paper, we describe a new disease, tentatively desig- differences between the sulfatase activities of normal fibro- nated Sanfilippo disease type D, that is characterized by the blasts were found. These observations suggest that N-acetyl- excessive excretion glucosamine4-6sulfate sulfatase activities degrading heparan clinical features of the Sanfilippo syndrome, sulfate and keratan sulfate, respectively, can be distinguished. of heparan sulfate, and the inability to release inorganic sulfate It is the activity directed toward heparan sulfate that is deficient from N-acetylglucosamine-6-sulfate residues of heparan sul- in these patients; we propose that this deficiency causes Sanfi- fate-derived oligosaccharides.
    [Show full text]
  • Hurler Syndrome (Mucopolysaccharidosis Type 1) in a Young Female Patient [Version 1; Peer Review: 3 Approved with Reservations]
    F1000Research 2020, 9:367 Last updated: 06 AUG 2021 CASE REPORT Case Report: Hurler syndrome (Mucopolysaccharidosis Type 1) in a young female patient [version 1; peer review: 3 approved with reservations] Sadaf Saleem Sheikh1, Dipak Kumar Yadav 2, Ayesha Saeed3 1Punjab Medical College, Faisalabad, Pakistan 2Nobel Medical College Teaching Hospital, Biratnagar, Nepal 3The Children’s Hospital, Institute of Child Health, Faisalabad, Pakistan v1 First published: 15 May 2020, 9:367 Open Peer Review https://doi.org/10.12688/f1000research.23532.1 Latest published: 15 May 2020, 9:367 https://doi.org/10.12688/f1000research.23532.1 Reviewer Status Invited Reviewers Abstract Hurler syndrome is a rare autosomal recessive disorder of 1 2 3 mucopolysaccharide metabolism. Here, we present the case of a young female patient who presented with features of respiratory version 1 distress. In addition, the patient had gingival hypertrophy, spaced 15 May 2020 report report report dentition, misaligned eruptive permanent dentition, microdontia, coarse facial features, low set ears, depressed nasal bridge, distended 1. Sanghamitra Satpathi , Hi-Tech Medical abdomen, pectus carinatum, umbilical hernia and J-shaped Sella Turcica on an X-ray of the skull. A diagnosis of Hurler syndrome College and Hospital, Rourkela, India (Mucopolysaccharidosis Type I) was made. The patient was kept on ventilator support from the third day; however, she died on the fifth 2. Alla N. Semyachkina , Research and day of admission. Enzyme replacement modality of treatment can Clinical Institute for Pediatrics of the Pirogov increase a patient's survival rate if an early diagnosis can be made. To Russian National Research Medical the best of our knowledge, only a few cases of Hurler syndrome have been reported in Pakistan.
    [Show full text]
  • Medical Genetics and Genomic Medicine in the United States of America
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by George Washington University: Health Sciences Research Commons (HSRC) Himmelfarb Health Sciences Library, The George Washington University Health Sciences Research Commons Pediatrics Faculty Publications Pediatrics 7-1-2017 Medical genetics and genomic medicine in the United States of America. Part 1: history, demographics, legislation, and burden of disease. Carlos R Ferreira George Washington University Debra S Regier George Washington University Donald W Hadley P Suzanne Hart Maximilian Muenke Follow this and additional works at: https://hsrc.himmelfarb.gwu.edu/smhs_peds_facpubs Part of the Genetics and Genomics Commons APA Citation Ferreira, C., Regier, D., Hadley, D., Hart, P., & Muenke, M. (2017). Medical genetics and genomic medicine in the United States of America. Part 1: history, demographics, legislation, and burden of disease.. Molecular Genetics and Genomic Medicine, 5 (4). http://dx.doi.org/10.1002/mgg3.318 This Journal Article is brought to you for free and open access by the Pediatrics at Health Sciences Research Commons. It has been accepted for inclusion in Pediatrics Faculty Publications by an authorized administrator of Health Sciences Research Commons. For more information, please contact [email protected]. GENETICS AND GENOMIC MEDICINE AROUND THE WORLD Medical genetics and genomic medicine in the United States of America. Part 1: history, demographics, legislation, and burden of disease Carlos R. Ferreira1,2 , Debra S. Regier2, Donald W. Hadley1, P. Suzanne Hart1 & Maximilian Muenke1 1National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 2Rare Disease Institute, Children’s National Health System, Washington, District of Columbia Correspondence Carlos R.
    [Show full text]