Investigation of Human Disease - Essay Example

?Investigation of Human Disease Patient Laboratory results: Prolonged PT and aPTT, decreased prothrombin %, decreased factors VII, IX, and X Differential Diagnosis: Liver cirrhosis, warfarin poisoning, VKOR mutation Liver cirrhosis is the terminal stage of chronic liver disease. Functionally, it synthesizes substances of almost all clotting factors necessary in coagulation process. Meanwhile, vitamin K, which is synthesized in the intestine by bacteria, is also necessary for hepatic synthesis of prothrombin, serum prothrombin conversion accelerator or factor VII, plasma thromboplastin component or factor IX, factor X, and protein C. Without vitamin K, the levels of these clotting factors will be significantly decreased leading to bleeding tendencies. Liver diseases such as cirrhosis, hepatitis, and atrophy all lead to failure of liver to secrete bile which is necessary for fat metabolism and its absorption together with vitamin K therefore, decreasing absorption of vitamin K as well. Laboratory results are prolonged bleeding time, PT and prolonged to normal PTT, normal platelet count, decreased levels of coagulation factors except VIII, decreased thrombin time and fibrinogen levels (Guyton & Hall, 2008). Warfarin (Coumadin), an oral anticoagulant functions by antagonizing vitamin K through the enzyme epoxide reductase which blocks vitamin K to be reduced in its active form. Thus the Vitamin K-dependent clotting factors as well as the anticoagulant proteins C and S which are produced in the liver are rendered inactive. About 97% of warfarin is tightly bound to plasma protein primarily albumin. Toxicity of the drug is dose dependent in which single intake of 10-20 mg only leads to mild intoxication. Meanwhile, chronic intake of small quantities of even 2-5 mg daily can result to considerable anticoagulation effects particularly with ingestion of interacting drugs. Likewise, superwarfarins are long acting and are utilized primarily as rodenticides can be highly potent resulting to extended adverse effects with dose as little as 1 mg. Laboratory findings are prolonged bleeding time and PT and decreased coagulation factors II, VII, IX, and X. The main consequence of warfarin or superwarfarin poisoning is bleeding (Olson, n.d.). VKOR (Vitamin K epoxide reductuse) can indicate dosages of warfarin and is encoded by the gene VKORC1. Vitamin K is fat-soluble and is needed as cofactor for the carboxylation of ?-carbon of the glutamic acid residues of the vitamin K-dependent clotting factors namely II, VII, IX, and X. The process is a vital stage for calcium and phospholipid to bind with these proteins. Epoxide reductase and ?-glutamylcarboxylase are important enzymes for metabolism and renewal of vitamin K. Genetic mutations involving these enzymes lead to their defective functioning eventually decreasing also the function of the vitamin-K dependent clotting factors. Laboratory findings are prolonged PT aPTT, and bleeding time, and decreased factors II, VII, IX, and X. Clinical manifestations of the disorder are characterized by hemorrhages ranging from mild to severe that may be apparent at birth. Medical interventions include replacement therapy with fresh frozen plasma or PCCs (Fauci, A., et al., 2008). Patient 2: Laboratory results: Marginal low thrombin time Diagnosis: Factor V Leiden Factor V Leiden mutation is present in about up to 15% of Caucasians. Genetic mutation of glutamine to arginine substitution at 506 position results to a factor V that is resistant to cleavage by protein C. Consequently, a significant antithrombotic counter-regulatory mechanism is lost resulting to a hypercoagulable state which may predispose a patient to develop thrombus formation (Kumar, et al., 2010). APC acts to inactivate factors Va and VIIIa via activation of thrombomodulin by thrombin. Protein C attaches with thrombomodulin producing then APC. Activated protein C also attaches with protein S on surface membranes of platelets. With this, APC can now lyse activated factors V and VIII. But with factor V Leiden, factor V becomes defiant to protein C, thus activated protein C resistance or APCR resulting to a factor V that is not blocked, or blocking is abnormally slower resulting to a thrombophilic status (Slusher, 2010). Laboratory findings are increased factor V and VIII and decreased thrombin time. Patient 3: Laboratory results: Prolonged PT and aPTT, increased thrombin time Diagnosis: Heparin treatment, dysfibrinogenemia Dysfibrinogenemia, which can be hereditary or acquired, is coagulation disorder due to defective structure of fibrinogen molecule leading to its abnormal functioning causing either bleeding or thrombosis wherein bleeding is caused by fibrinogen mutation while thrombosis is caused by mutations that inhibit anticoagulant or profibrinolytic activities of fibrin. Inherited dysfibrinogenemia is an autosomal dominant trait and is due to mutations in the coding region of the fibrinogen A?, B?, or ? gene. It is diagnosed by laboratory test and analysis of the fibrinogen protein or genes. Most do not manifest bleeding but abnormal thrombin time. Acquired dysfibrinogenemia is typically the result of liver or biliary diseases resulting to increased sialylation of carbohydrate side chains of the fibrinogen molecule reducing fibrin polymerization rate. Positive screening tests include thrombin time and reptilase time which is prolonged due to inhibition of fibrinopeptide A release or fibrin monomer polymerization. A test for confirmation is a decreased fibrinogen activity-antigen ratio (Cunningham, et al., 2002) Patient 4: Laboratory results: prolonged aPTT, decreased factor VIII Diagnosis: Hemophilia A. Hemophilia A or classic hemophilia is an X-linked recessive heritable bleeding disorder due to mutations of the gene coding factor VIII. Factor VIII is composed of two components in which the smaller component is more involved in the intrinsic pathway of blood coagulation, the deficiency of which results to classic hemophilia. The most common type of hemophilia A is secondary to an inversion of the intron 22 sequence, which is demonstrated in 40% of patients with severe hemophilia. Laboratory test findings are prolonged PTT, normal PT, and decreased level of factor VIII. Hemophilia A manifests variably according to the level of factor VIII activity, classified as mild, moderate, or severe. Symptoms present with easy bruising and massive bleeding after injury or surgical operations. Instantaneous bleeding commonly exists in body parts ordinarily subjected to injury such as the joints (Fauci, et al., 2010; & Kumar, et al., 2010). Patient 5: Laboratory results: Prolonged PT and aPTT, decreased prothrombin % and factors VII, IX, and X Differential Diagnosis: VKOR mutation, warfarin poisoning, liver cirrhosis Patient 6: Laboratory results: Prolonged bleeding time Diagnosis: Aspirin treatment Aspirin (acetylsalicylic acid) is indicated as analgesic, antipyretic, and anti-inflammatory drug. Aspirin intake of healthy individuals increases bleeding time due to irreversible acetylation of cyclooxygenase resulting to reduced thromboxane A2. It is indicated as prophylaxis of thromboembolism particularly in heart and cerebral blood circulation. It does not change the platelet count, hematocrit, or hemoglobin content. Caution is observed with long term therapy since there is a risk of prolonged bleeding time along with blood loss from the gastrointestinal tract. Likewise, it can cause a mild level of hemolysis in persons suffering from glucose-6-phosphate deficiency. Salicylates can consequently lead to liver injury especially with clients taking increased doses of the drug attaining a plasma concentration level greater than 150 ug/ml. Thus, it is contraindicated with liver diseases, vitamin K deficiency, hemophilia, and hypoprothrombinemia due to possibility of bleeding. In addition, it is involved in severe liver damage and Reye’s syndrome (Brunton, 2006). Patient 7: Laboratory results: Prolonged PT, aPTT, thrombin time, and reptilase time; decreased fibrinogen; and increased bleeding Diagnosis: Heparin treatment Heparin is an anticoagulant used in high concentrations to inhibit intravascular thrombosis. Heparin molecule becomes activated only with its linking to antithrombin III, a glycosylated, single chain polypeptide with 432 amino acid residues (Olson & Chuan, 2002) which is a potent anticoagulant by lysing thrombin, factors IX, X, XI, and XII. It is continuously synthesized by mast cells and basophils which are located in the pericapillary connective tissues. It increases the rate of thrombin-antithrombin reaction by functioning like a catalyst template where the inhibitor and the protease bind. Heparin therapy is monitored with aPTT and clotting time which is 1.8 to 2.5 times the normal mean aPTT value. Due to its rapid onset of action, it is used as initial treatment for venous thrombosis and pulmonary embolism (Hirsh, et al., 2001). High doses are given during cardiopulmonary bypass and also for long term use to clients with contraindicated use of warfarin. Laboratory findings are increased thrombin time with normal platelet count (Brunton, et al., 2006). Patient 8: Laboratory results: Prolonged aPTT, decreased factor IX Diagnosis: Hemophilia B Hemophilia B, factor IX deficiency, or Christmas disease is an X-linked recessive trait and manifests varying degree of clinical severity which predisposes men and homozygous women, similar to Hemophilia A (Kumar, et al., 2010). Various mutations of the genes encoding factor IX, which are partial gene deletions and point and missense mutations result to decrease functioning of factor IX proteins (Murray, 2006). Laboratory results are prolonged PTT, normal PT and decreased factor IX. Prolonged PTT suggests deficiency of factors involved in intrinsic pathway of blood coagulation which are factors I, II, V, VIII, IX, X, XI, and XII. Normal PT tests clotting factors I, II, V, VII, and X implying that this pathway is not affected. Clinically, hemophilia B and A are indistinguishable which also presents with hemorrhagic episodes. Diagnosis of the disease is only possible by assay of the factor levels. Clients are given intravenous infusions of recombinant factor IX (Fauci, et al., 2010). Patient 9: Laboratory results: Prolonged PT, aPTT, thrombin time, and reptilase time; and decreased fibrinogen, prothrombin % and factors VII, IX, and X. Differential diagnosis: VKOR mutation, liver cirrhosis, dysfibrinogenaemia Patient 10: Laboratory results: Prolonged bleeding time, decreased platelet count Diagnosis: Bernard-Soulier syndrome Bernard-Soulier syndrome is an autosomal recessive hereditary disorder resulting to a deficient platelet membrane glycoprotein complex Ib-IX which is a receptor for von Willebrand factor (vWF). The faulty adhesion of platelets to subendothelial extracellular matrix (ECM) results to hemorrhagic episodes (Fauci, et al., 2010; & Kumar, et al., 2010). Platelet attachment to ECM is mediated through contact with vWF, which functions to connect surface receptors of platelets and exposed collagen. vWF-GpIb complex is important to surmount the high shear pressures of the flowing blood. Thus, with the significance of this interplay, hereditary deficiencies of vWF (von Willebrand disease) or its receptor (Bernard-Soulier syndrome) consequently lead to hemorrhagic diseases. Laboratory findings reveal marginal to prolonged bleeding time, variable thrombocytopenia, huge defective platelets, and platelet count commonly ranges below 30 to 200 ? 103/?L which commonly manifests with menometrorrhagia, epistaxis, bleeding gums, and ecchymosis. Confirmatory tests are flow cytometry and platelet aggregometry (Pham & Wang, 2007). References: Blomback B. Studies on the action of thrombic enzymes on bovine fibrinogen as measured by N-terminal analysis. Arkiv Kemi.12:321–335, 1958 ; Holleman WH, Weiss LJ. The thrombin-like enzyme from Bothrops atrox snake venom: properties of the enzyme purified by affinity chromatography on p-aminobenzamidine-substituted agarose. J Biol Chem ;251:1663–1669, 1976 Brunton, L., et al. Goodman and Gilman’s The Pharmacological Basis of Therapeutics 11th ed the McGraw-Hill Companies, Inc., 2006 Cunningham, M., et al. Laboratory Diagnosis of Dysfibrinogenemia PhD Arch Pathol Lab Med—Vol 126, 2002 Fauci, A., et al. Harrison’s Principles of Internal Medicine 17th ed. The McGraw-Hill Companies, Inc., 2008 Fritsma, G. “Blood Thinners” Coumadin, Heparin, and Coagulation Laboratory Testing, n.d.) Guyton, A. & Hall J. Textbook of Medical Physiology 11th ed. Elsevier Inc., 2006 Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia: report on a study of the SSC Subcommittee of Fibrinogen. Thromb Haemost.73:151–161, 1995 Hirsh, J., et al. Guide to anticoagulant therapy. Heparin: a statement for healthcare professionals form the American Heart Association. Circulation, 103: 2994-3018, 2001 Kasper, D., et al. Harrisons Manual of Medicine 16th ed. The McGraw-Hill Companies, Inc., 2005 Kent R Olson, MD Toxicity, Warfarin and Superwarfarins Available at http://emedicine.medscape.com Retrieved April 8, 2011 Kumar, V., et al. Robbins and Cotran Pathologic Basis of Disease 8th ed Saunders Elsevier, 2010 LeBlond, R., DeGowin, R., & Brown, D. DeGowin’s Diagnostic Examination: The Complete Guide to Assessment Examination Differential Diagnosis 8th ed. The McGraw Hill Companies, 2004 Olson, S. & Chuang Y. Heparin activated antithrombin anticoagulant function by generating new interaction sites (exosites) for blood clotting proteinases. Trends Cardiovasc. Med. 12:331-338, 2002 Pham, A. & Wang, J. (2007) Bernard-Soulier Syndrome: An Inherited Platelet Disorder. Archives of Pathology & Laboratory Medicine:Vol. 131, No. 12, pp. 1834-1836. 2007Table of Contents Page 1p36 Deletion Syndrome 1q21.1 Microdeletion 16p11.2 Microdeletion 15q13.3 Microdeletion 17q21.31 Microdeletion Syndrome 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia 22q11.2 Deletion Syndrome 22q11.2 Duplication 22q13.3 Deletion Syndrome 2q37 Deletion Syndrome 3-M Syndrome 3-Methylglutaconic Aciduria Type 3 46,XX Testicular Disorder of Sex Development 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis ALK-Related Neuroblastoma Susceptibility ALS2-Related Disorders APC-Associated Polyposis Conditions ARSACS ATP6V0A2-Related Cutis Laxa ATP7A-Related Copper Transport Disorders Aceruloplasminemia Achondrogenesis Type 1B Achondroplasia Achromatopsia Acid Sphingomyelinase Deficiency Adenosine Deaminase Deficiency Adult Polyglucosan Body Disease Aicardi Syndrome Aicardi-Goutieres Syndrome Alagille Syndrome Alexander Disease Alkaptonuria Alpha-Mannosidosis Alpha-Thalassemia X-Linked Intellectual Disability Syndrome Alpha-Thalassemia Alpha1-Antitrypsin Deficiency Alstrom Syndrome Alzheimer Disease Overview Amish Lethal Microcephaly Amyotrophic Lateral Sclerosis Overview Andersen-Tawil Syndrome Androgen Insensitivity Syndrome Angelman Syndrome Aniridia Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Syndrome Anophthalmia / Microphthalmia Overview Arginase Deficiency Argininosuccinate Lyase Deficiency Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant Arts Syndrome Arylsulfatase A Deficiency Ataxia with Oculomotor Apraxia Type 1 Ataxia with Oculomotor Apraxia Type 2 Ataxia with Vitamin E Deficiency Ataxia-Telangiectasia Atelosteogenesis Type 2 Atypical Hemolytic-Uremic Syndrome Autism Spectrum Disorders Autoimmune Lymphoproliferative Syndrome Autosomal Dominant Hyper IgE Syndrome Autosomal Dominant Nocturnal Frontal Lobe Epilepsy Autosomal Dominant Partial Epilepsy with Auditory Features Autosomal Recessive Congenital Ichthyosis BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer BSCL2-Related Neurologic Disorders/Seipinopathy Baller-Gerold Syndrome Bardet-Biedl Syndrome Beckwith-Wiedemann Syndrome Benign Familial Neonatal Seizures Berardinelli-Seip Congenital Lipodystrophy Best Vitelliform Macular Dystrophy Beta-Thalassemia Biotinidase Deficiency Birt-Hogg-Dube Syndrome Blepharophimosis, Ptosis, and Epicanthus Inversus Bloom's Syndrome Branchiootorenal Spectrum Disorders Brugada Syndrome CADASIL CARASIL CATSPER-Related Male Infertility CDC73-Related Disorders CFTR-Related Disorders CHARGE Syndrome CHMP2B-Related Frontotemporal Dementia CLCN7-Related Osteopetrosis COL4A1-Related Disorders Calpainopathy Campomelic Dysplasia Camurati-Engelmann Disease Canavan Disease Cardiofaciocutaneous Syndrome Carney Complex Carnitine Palmitoyltransferase 1A Deficiency Carnitine Palmitoyltransferase II Deficiency Catecholaminergic Polymorphic Ventricular Tachycardia Caveolinopathies Celiac Disease Central Core Disease Cerebral Cavernous Malformation, Familial Cerebrotendinous Xanthomatosis Char Syndrome Charcot-Marie-Tooth Hereditary Neuropathy Overview Charcot-Marie-Tooth Neuropathy Type 1 Charcot-Marie-Tooth Neuropathy Type 2 Charcot-Marie-Tooth Neuropathy Type 2A Charcot-Marie-Tooth Neuropathy Type 2D/Distal Spinal Muscular Atrophy V Charcot-Marie-Tooth Neuropathy Type 4 Charcot-Marie-Tooth Neuropathy Type 4A Charcot-Marie-Tooth Neuropathy Type 4C Charcot-Marie-Tooth Neuropathy X Type 1 Charcot-Marie-Tooth Neuropathy X Type 5 Charcot-Marie-Tooth Neuropathy Type 2E/1F Chediak-Higashi Syndrome Cherubism Childhood Ataxia with Central Nervous System Hypomyelination/Vanishing White Matter Chondrodysplasia Punctata 1, X-Linked Recessive Chorea-Acanthocytosis Choroideremia Citrin Deficiency Citrullinemia Type I Cleidocranial Dysplasia Cockayne Syndrome Coffin-Lowry Syndrome Cohen Syndrome Cold-Induced Sweating Syndrome including Crisponi Syndrome Collagen IV-Related Nephropathies (Alport Syndrome and Thin Basement Membrane Nephropathy) Collagen Type VI-Related Disorders Common Variable Immune Deficiency Overview Congenital Cataracts, Facial Dysmorphism, and Neuropathy Congenital Central Hypoventilation Syndrome Congenital Contractural Arachnodactyly Congenital Diaphragmatic Hernia Overview Congenital Disorder of Glycosylation Type 1a Congenital Disorders of Glycosylation Overview Congenital Dyserythropoietic Anemia Type I Congenital Fiber-Type Disproportion Congenital Fibrosis of the Extraocular Muscles Congenital Hepatic Fibrosis Overview Congenital Muscular Dystrophy Overview Congenital Myasthenic Syndromes Congenital Stromal Corneal Dystrophy Cornelia de Lange Syndrome Costello Syndrome Craniofacial Microsomia Overview Craniometaphyseal Dysplasia, Autosomal Dominant Creatine Deficiency Syndromes Cystinosis Cytochrome P450 Oxidoreductase Deficiency DCX-Related Disorders DFNA2 Nonsyndromic Hearing Loss DGUOK-Related Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy DRPLA Deafness and Hereditary Hearing Loss Overview Deafness-Dystonia-Optic Neuronopathy Syndrome Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II Diabetes Mellitus, 6q24-Related Transient Neonatal Diamond-Blackfan Anemia Diastrophic Dysplasia Dilated Cardiomyopathy Overview Disorders of Intracellular Cobalamin Metabolism Donnai-Barrow Syndrome Dopamine Beta-Hydroxylase Deficiency Duane Syndrome Dysferlinopathy Dyskeratosis Congenita Dystonia Overview Dystrophic Epidermolysis Bullosa Dystrophinopathies ELANE-Related Neutropenia Early-Onset Familial Alzheimer Disease Early-Onset Primary Dystonia (DYT1) Ehlers-Danlos Syndrome, Classic Type Ehlers-Danlos Syndrome, Hypermobility Type Ehlers-Danlos Syndrome, Kyphoscoliotic Form Ehlers-Danlos Syndrome, Vascular Type Emanuel Syndrome Emery-Dreifuss Muscular Dystrophy Enlarged Parietal Foramina/Cranium Bifidum Epidermolysis Bullosa Simplex Epidermolysis Bullosa with Pyloric Atresia Epimerase Deficiency Galactosemia Episodic Ataxia Type 1 Episodic Ataxia Type 2 Esophageal Atresia/Tracheoesophageal Fistula Overview FBLN5-Related Cutis Laxa FGFR-Related Craniosynostosis Syndromes FLNB-Related Disorders FMR1-Related Disorders FRMD7-Related Infantile Nystagmus Fabry Disease Facioscapulohumeral Muscular Dystrophy Factor V Leiden Thrombophilia Familial Acute Myeloid Leukemia (AML) with Mutated CEBPA Familial Dysautonomia Familial Exudative Vitreoretinopathy, Autosomal Dominant Familial Hemiplegic Migraine Familial Hyperinsulinism (FHI) Familial Hypertrophic Cardiomyopathy Overview Familial Idiopathic Basal Ganglia Calcification Familial Juvenile Hyperuricemic Nephropathy Type 2 Familial Lipoprotein Lipase Deficiency Familial Mediterranean Fever Familial Mosaic Monosomy 7 Syndrome Familial Paroxysmal Kinesigenic Dyskinesia Familial Paroxysmal Nonkinesigenic Dyskinesia Familial Transthyretin Amyloidosis Fanconi Anemia Feingold Syndrome Focal Dermal Hypoplasia Free Sialic Acid Storage Disorders Friedreich Ataxia Fryns Syndrome Fukuyama Congenital Muscular Dystrophy Fumarate Hydratase Deficiency GATA1-Related X-Linked Cytopenia GRN-Related Frontotemporal Dementia GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia Galactosemia Gaucher Disease Geleophysic Dysplasia Genetic Prion Diseases Giant Axonal Neuropathy Glucose Transporter Type 1 Deficiency Syndrome Glycine Encephalopathy Glycogen Storage Disease Type I Glycogen Storage Disease Type II (Pompe Disease) Glycogen Storage Disease Type III Glycogen Storage Disease Type V Glycogen Storage Disease Type VI Greig Cephalopolysyndactyly Syndrome HFE-Associated Hereditary Hemochromatosis Hand-Foot-Genital Syndrome Hemophagocytic Lymphohistiocytosis, Familial Hemophilia A Hemophilia B Hepatic Veno-Occlusive Disease with Immunodeficiency Hereditary Ataxia Overview Hereditary Diffuse Gastric Cancer Hereditary Folate Malabsorption Hereditary Hemorrhagic Telangiectasia Hereditary Leiomyomatosis and Renal Cell Cancer Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum Hereditary Multiple Osteochondromas Hereditary Neuralgic Amyotrophy Hereditary Neuropathy with Liability to Pressure Palsies Hereditary Non-Polyposis Colon Cancer Hereditary Paraganglioma-Pheochromocytoma Syndromes Hereditary Sensory and Autonomic Neuropathy IV Hereditary Sensory and Autonomic Neuropathy Type II Hereditary Sensory Neuropathy Type I Hereditary Spastic Paraplegia Overview Heritable Pulmonary Arterial Hypertension Hermansky-Pudlak Syndrome Hexosaminidase A Deficiency Hidrotic Ectodermal Dysplasia 2 Hirschsprung Disease Overview Holoprosencephaly Overview Holt-Oram Syndrome Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency Huntington Disease Huntington Disease-Like 2 Hutchinson-Gilford Progeria Syndrome Hyalinosis, Inherited Systemic Hydroxymethylbilane Synthase (HMBS) Deficiency Hyperekplexia Hyperkalemic Periodic Paralysis Type 1 Hypochondroplasia Hypohidrotic Ectodermal Dysplasia Hypokalemic Periodic Paralysis Hypomyelination and Congenital Cataract Hypophosphatasia IPEX Syndrome IRF6-Related Disorders Inclusion Body Myopathy 2 Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia Incontinentia Pigmenti Infantile Neuroaxonal Dystrophy Infantile-Onset Spinocerebellar Ataxia Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency Overview Jervell and Lange-Nielsen Syndrome Joubert Syndrome Junctional Epidermolysis Bullosa Juvenile Hereditary Hemochromatosis Juvenile Polyposis Syndrome Kallmann Syndrome Kleefstra Syndrome Krabbe Disease L1 Syndrome LEOPARD Syndrome LIS1-Associated Lissencephaly/Subcortical Band Heterotopia LMNA-Related Dilated Cardiomyopathy LRRK2-Related Parkinson Disease Laing Distal Myopathy Leber Congenital Amaurosis Leber Hereditary Optic Neuropathy Legius Syndrome Lenz Microphthalmia Syndrome Lesch-Nyhan Syndrome Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation Li-Fraumeni Syndrome Limb-Girdle Muscular Dystrophy Overview Loeys-Dietz Syndrome Low ?-GT Familial Intrahepatic Cholestasis Lowe Syndrome Lymphedema-Distichiasis Syndrome Lymphoproliferative Disease, X-Linked Lysinuric Protein Intolerance MAPT-Related Disorders MCT8 (SLC16A2)-Specific Thyroid Hormone Cell Transporter Deficiency MECP2 Duplication Syndrome MECP2-Related Disorders MED12-Related Disorders MELAS MERRF MYH9-Related Disorders Majeed Syndrome Malignant Hyperthermia Susceptibility Manitoba Oculotrichoanal Syndrome Maple Syrup Urine Disease Marfan Syndrome Marinesco-Sjogren Syndrome McKusick-Kaufman Syndrome McLeod Neuroacanthocytosis Syndrome Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Megalencephalic Leukoencephalopathy with Subcortical Cysts Methylmalonic Acidemia Microphthalmia with Linear Skin Defects Syndrome Milroy Disease Mitochondrial DNA Deletion Syndromes Mitochondrial DNA-Associated Leigh Syndrome and NARP Mitochondrial Disorders Overview Mitochondrial Neurogastrointestinal Encephalopathy Disease Mowat-Wilson Syndrome Mucolipidosis II Mucolipidosis III Alpha/Beta Mucolipidosis III Gamma Mucolipidosis IV Mucopolysaccharidosis Type I Mucopolysaccharidosis Type II Muenke Syndrome Multiminicore Disease Multiple Cutaneous and Mucosal Venous Malformations Multiple Endocrine Neoplasia Type 1 Multiple Endocrine Neoplasia Type 2 Multiple Epiphyseal Dysplasia, Dominant Multiple Epiphyseal Dysplasia, Recessive Multiple Sclerosis Overview Myoclonus-Dystonia Myofibrillar Myopathy Myopathy with Deficiency of ISCU Myostatin-Related Muscle Hypertrophy Myotonia Congenita Myotonic Dystrophy Type 1 Myotonic Dystrophy Type 2 NDP-Related Retinopathies NSDHL-Related Disorders Nail-Patella Syndrome Nemaline Myopathy Nephrogenic Diabetes Insipidus Neuroferritinopathy Neurofibromatosis 1 Neurofibromatosis 2 Neuronal Ceroid-Lipofuscinoses Nevoid Basal Cell Carcinoma Syndrome Niemann-Pick Disease Type C Nijmegen Breakage Syndrome Nonsyndromic Hearing Loss and Deafness, DFNA3 Nonsyndromic Hearing Loss and Deafness, DFNB1 Nonsyndromic Hearing Loss and Deafness, Mitochondrial Noonan Syndrome OTOF-Related Deafness Ocular Albinism, X-Linked Oculocutaneous Albinism Type 1 Oculocutaneous Albinism Type 2 Oculocutaneous Albinism Type 4 Oculopharyngeal Muscular Dystrophy Optic Atrophy Type 1 Oral-Facial-Digital Syndrome Type I Osteogenesis Imperfecta Otopalatodigital Spectrum Disorders PINK1 Type of Young-Onset Parkinson Disease PLP1-Related Disorders POLG-Related Disorders PROP1- Related Combined Pituitary Hormone Deficiency (CPHD) PTEN Hamartoma Tumor Syndrome (PHTS) Pachyonychia Congenita Pallister-Hall Syndrome Pantothenate Kinase-Associated Neurodegeneration Parkin Type of Juvenile Parkinson Disease Parkinson Disease Overview Pendred Syndrome/DFNB4 Permanent Neonatal Diabetes Mellitus Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum Perry Syndrome Peters Plus Syndrome Peutz-Jeghers Syndrome Phenylalanine Hydroxylase Deficiency Phosphoribosylpyrophosphate Synthetase Superactivity Polycystic Kidney Disease, Autosomal Dominant Polycystic Kidney Disease, Autosomal Recessive Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL) Polymicrogyria Overview Pontocerebellar Hypoplasia Type 2 and Type 4 Prader-Willi Syndrome Primary Autosomal Recessive Microcephaly Primary Ciliary Dyskinesia Primary Congenital Glaucoma Primary Hyperoxaluria Type 1 Primary Hyperoxaluria Type 2 Progressive Myoclonus Epilepsy, Lafora Type Progressive Myoclonus Epilepsy with Ataxia Prothrombin-Related Thrombophilia Pseudoachondroplasia Pseudoxanthoma Elasticum Pulmonary Fibrosis, Familial Pyridoxine-Dependent Seizures Pyruvate Carboxylase Deficiency RASA1-Related Disorders ROR2-Related Robinow Syndrome Rapid-Onset Dystonia Parkinsonism Red-Green Color Vision Defects Refsum Disease Renal Coloboma Syndrome Retinitis Pigmentosa Overview Retinoblastoma Rhizomelic Chondrodysplasia Punctata Type 1 Roberts Syndrome Romano-Ward Syndrome Rothmund-Thomson Syndrome Rubinstein-Taybi Syndrome Russell-Silver Syndrome SALL4-Related Disorders SCN1A-Related Seizure Disorders SCN9A-Related Inherited Erythromelalgia SHOX-Related Haploinsufficiency Disorders SOST-Related Sclerosing Bone Dysplasias SOX2-Related Eye Disorders SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form, with Mild Methylmalonic Aciduria SYNE1-Related Autosomal Recessive Cerebellar Ataxia Saethre-Chotzen Syndrome Schimke Immunoosseous Dysplasia Shprintzen-Goldberg Syndrome Shwachman-Diamond Syndrome Sialuria Sickle Cell Disease Simpson-Golabi-Behmel Syndrome Smith-Lemli-Opitz Syndrome Smith-Magenis Syndrome Sotos Syndrome Spastic Paraplegia 3A Spastic Paraplegia Type 4 Spastic Paraplegia 7 Spastic Paraplegia 8 Spastic Paraplegia Type 11 Spinal Muscular Atrophy Spinal Muscular Atrophy, X-Linked Infantile Spinal and Bulbar Muscular Atrophy Spinocerebellar Ataxia Type 1 Spinocerebellar Ataxia Type 2 Spinocerebellar Ataxia Type 3 Spinocerebellar Ataxia Type 6 Spinocerebellar Ataxia Type 7 Spinocerebellar Ataxia Type 8 Spinocerebellar Ataxia Type 10 Spinocerebellar Ataxia Type 11 Spinocerebellar Ataxia Type 12 Spinocerebellar Ataxia Type13 Spinocerebellar Ataxia Type 14 Spinocerebellar Ataxia Type 15 Spinocerebellar Ataxia Type 17 Spinocerebellar Ataxia Type 20 Spinocerebellar Ataxia with Axonal Neuropathy, Autosomal Recessive Spondylocostal Dysostosis, Autosomal Recessive Spondylothoracic Dysostosis Stickler Syndrome Succinic Semialdehyde Dehydrogenase Deficiency TARDBP-Related Amyotrophic Lateral Sclerosis TFR2-Related Hereditary Hemochromatosis Tetra-Amelia Syndrome Thanatophoric Dysplasia The Organic Acidemias: An Overview Thiamine-Responsive Megaloblastic Anemia Syndrome Thoracic Aortic Aneurysms and Aortic Dissections Thrombocytopenia Absent Radius Syndrome Timothy Syndrome Tourette Disorder Overview Townes-Brocks Syndrome Treacher Collins Syndrome Trimethylaminuria Troyer Syndrome Tuberous Sclerosis Complex Tyrosine Hydroxylase Deficiency Tyrosinemia Type 1 UMOD-Associated Kidney Disease Udd Distal Myopathy Unverricht-Lundborg Disease Urea Cycle Disorders Overview Usher Syndrome Type I Usher Syndrome Type II von Willebrand Disease VCAN-Related Vitreoretinopathy VLDLR-Associated Cerebellar Hypoplasia Very Long Chain Acyl-Coenzyme A Dehydrogenase Deficiency Von Hippel-Lindau Syndrome WAS-Related Disorders WFS1-Related Disorders Waardenburg Syndrome Type I Weill-Marchesani Syndrome Werner Syndrome Williams Syndrome Wilms Tumor Overview Wilson Disease Wolf-Hirschhorn Syndrome X-Linked Adrenal Hypoplasia Congenita X-Linked Adrenoleukodystrophy X-Linked Agammaglobulinemia X-Linked Congenital Stationary Night Blindness X-Linked Dystonia-Parkinsonism X-Linked Hyper IgM Syndrome X-Linked Juvenile Retinoschisis X-Linked Myotubular Myopathy X-Linked Opitz G/BBB Syndrome X-Linked Periventricular Heterotopia X-Linked Severe Combined Immunodeficiency X-Linked Sideroblastic Anemia and Ataxia X-Linked Spondyloepiphyseal Dysplasia Tarda Xeroderma Pigmentosum Y Chromosome Infertility ZAP70-Related Severe Combined Immunodeficiency Glossary Instructions Illustrated Glossary Slusher, K. Factor V Leiden: A Case Study and Review .January/February 2010 - Volume 29 - Issue 1 - pp 6-10 doi: 10.1097/DCC.0b013e3181be4985 Read More