DOCSLIB.ORG

Essential Revision Notes for MRCP Fourth Edition

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Essential Revision Notes for MRCP Fourth Edition Essential Revision Notes for MRCP Fourth Edition edited by Philip A Kalra MA MB BChir FRCP MD Consultant and Honorary Professor of Nephrology, Salford Royal NHS Foundation Trust and The University of Manchester Contents Contributors to Fourth Edition vii Contributors toThird Edition x Permissions xii Preface to the Fourth Edition xiii CHAPTER 1. Cardiology 1 J E R Davies, S Nijjer 2. ClinicalPharmacology,ToxicologyandPoisoning 65 S Waring 3. Dermatology 87 H Robertshaw 4. Endocrinology 107 T Kearney, S Giritharan, M Kumar 5. Epidemiology 143 J Ritchie 6. Gastroenterology 157 S Lal, D H Vasant 7. Genetics 205 E Burkitt Wright 8. Genito-urinary Medicine and AIDS 223 B Goorney 9. Haematology 237 K Patterson 10. Immunology 279 J Galloway 11. Infectious Diseases andTropical Medicine 295 C L van Halsema 12. Maternal Medicine 329 L Byrd v Contents 13. Metabolic Diseases 359 S Sinha 14. Molecular Medicine 395 K Siddals 15. Nephrology 435 P Kalra 16. Neurology 493 M Jones, C Kobylecki, D Rog 17. Ophthalmology 561 K Smyth 18. Psychiatry 583 E Sampson 19. Respiratory Medicine 611 H Green 20. Rheumatology 657 M McMahon 21. Statistics 685 E Koutoumanou Index 703 vi Chapter 4 Endocrinology CONTENTS 4.1 Hormone action 4.4 Hyponatraemia and SIADH 4.1.1 Types of hormone 4.1.2 Hormones that act at the cell 4.5 The thyroid gland surface 4.5.1 Hyperthyroidism and 4.1.3 Hormones that act hypothyroidism intracellularly 4.5.2 Causes of thyrotoxicosis 4.1.4 Hormone resistance syndromes 4.5.3 Thyroid cancer and nodules 4.5.4 Drugs and the thyroid 4.2 Speci¢c hormone physiology 4.5.5 Autoimmunity and eye signs in 4.2.1 Hormones in illness thyroid disease 4.2.2 Hormone changes in obesity 4.5.6 Thyroid function tests 4.2.3 Hormones in pregnancy 4.2.4 Investigations in endocrinology 4.6 Adrenal disease and hirsutism 4.2.5 Growth hormone 4.6.1 Cushing syndrome 4.2.6 Prolactin 4.6.2 Primary hyperaldosteronism 4.2.7 Adrenal steroids 4.6.3 Congenital adrenal hyperplasia 4.2.8 Thyroid hormone metabolism 4.6.4 Hypoadrenalism 4.2.9 Renin–angiotensin–aldosterone 4.6.5 Polycystic ovary syndrome and 4.2.10 Calcium, PTH and vitamin D hirsutism 4.2.11 Atrial natriuretic peptide 4.7 Phaeochromocytoma and 4.3 The pituitary gland multiple endocrine neoplasia 4.3.1 Anatomy syndromes 4.3.2 Pituitary tumours 4.3.3 Diabetes insipidus 4.8 Puberty/growth/intersex 4.3.4 Acromegaly 4.8.1 Normal puberty 4.3.5 Prolactinomas 4.8.2 Precocious puberty 4.3.6 Hypopituitarism and growth 4.8.3 Delayed puberty/short stature hormone deficiency in adults 4.8.4 Intersex 107 Essential Revision Notes for MRCP 4.9 Diabetes mellitus 4.9.1 Risk factors and clinical features of types 1 and 2 diabetes mellitus 4.9.2 Diagnostic criteria for diabetes 4.9.3 Treatment of type 1 diabetes 4.9.4 Treatment of type 2 diabetes 4.9.5 Glycated HbA1c 4.9.6 Microvascular and macrovascular complications of diabetes 4.9.7 Autonomic neuropathy 4.10 Hypoglycaemia 4.10.1 Hypoglycaemia in diabetes mellitus 4.10.2 Hypoglycaemia unrelated to diabetes 108 Endocrinology Endocrinology 4.1 HORMONE ACTION bind to an intracellular receptor and affect gene transcription. Glucagon is not a steroid or an amine There are three main types of hormone: so it must be a polypeptide hormone, which has a • amine short circulation half-life, acts via a cell surface • steroid receptor and probably utilises a second messenger • peptide. (adenosine cyclic monophosphate, or cAMP, in fact). Knowing which category a particular hormone fits into makes it possible to guess much of its physiol- ogy. Thyroxine is an exception to this, as shown 4.1.2 Hormones that act at the cell below. surface Peptide and amine hormones act at the cell surface 4.1.1 Types of hormone via specific membrane receptors. The signal is trans- • Amine: catecholamines, serotonin, thyroxine mitted intracellularly by one of three mechanisms: • Steroid: cortisol, aldosterone, androgens, • Via cAMP oestrogens , progestogens and vitamin D • Via a rise in intracellular calcium • Peptide: everything else! (made up of a series of • Via receptor tyrosine kinases. amino acids). Thyroxine is chemically an amine but it acts like a If in doubt, assume the action of a peptide or amine steroid. Vitamin D has the structure of a steroid hormone (excluding thyroxine) is via cAMP, unless hormone and it acts like one. it is insulin or has the word ‘growth’ in its name, in which case it is likely to act via a receptor tyrosine kinase (Table 4.1). Amines/peptides • Short half-life (minutes) Cyclic AMP and G-proteins • Secretion may be pulsatile • Act on a cell surface receptor Hormone receptors linked to cAMP (eg thyroid- • Often act via a second messenger stimulating hormone [TSH] receptor) typically have seven transmembrane domains. The receptor does not directly generate cAMP but acts via separate ‘G- Steroids proteins’ on the cell surface which, in turn, interact with the cAMP-generating enzyme, adenylyl • Longer biological half-life (hours) cyclase, on the cell surface. (See Figure 14.4 in • Act on an intracellular receptor Chapter 14, Molecular Medicine.) • Act on DNA to alter gene expression Hormones that raise the level of cAMP intracellu- larly (all hormones in this category except somato- This information can be used to predict hormone statin) act via a stimulatory G-protein, ‘Gs’. action, eg aldosterone is a steroid hormone so it Hormones that lower the level of cAMP (somato- must have a biological half-life of several hours, statin) act via an inhibitory G-protein, ‘G i’. 109 Essential Revision Notes for MRCP Table 4.1 Mechanisms of hormone action Via cAMP Via Ca 2+ Via receptor tyrosine kinases Adrenaline (â receptors) GnRH Insulin All pituitary hormones except GH, PRL TRH GH, PRL Glucagon Adrenaline (Æ receptors) ‘Growth factors’: IGF-1, EGF Somatostatin cAMP, adenosine cyclic monophosphate; EGF, epidermal growth factor; GH, growth hormone; GnRH, gonado- trophin-releasing hormone; IGF-1, insulin-like growth factor 1; PRL, prolactin; TRH, thyrotrophin-releasing hormone. G-proteins are important in endocrinology because pseudohypoparathyroidism). The dysmorphic mutations in Gs have been found to be associated bone features are sometimes referred to as with certain diseases: ‘Albright’s hereditary osteodystrophy’ and can be present in either the maternally or the paternally • Acromegaly: 40% of patients with acromegaly inherited form. have an activating somatic mutation of Gs in their pituitary tumour. As a result, the cells are always ‘switched on’ and continuously make 2+ growth hormone (GH), resulting in acromegaly Intracellular Ca • McCune–Albright syndrome: an activating Some hormones release intracellular Ca 2+ as a sec- mutation of Gs early in embryonic development ond messenger (see Table 4.1 for examples). The causes hyperfunction of one or more endocrine receptors for these hormones activate different G- glands with the following sequelae: precocious proteins (eg Gq), which in turn activate the cyto- puberty (gonad hyperfunction), acromegaly (GH plasmic enzyme phospholipase C (PLC). PLC re- hypersecretion), Cushing syndrome (adrenal leases the small molecule inositol-1,4,5- gland hyperfunction), thyrotoxicosis or triphosphate (IP3) from membrane phospholipids. hyperparathyroidism. The syndrome is IP3 in turn binds to the IP3-sensitive receptor on the associated with cafe´-au-lait spots and endoplasmic reticulum within the cell, causing Ca 2+ polyostotic fibrous dysplasia. As the mutation to be released from stores in the endoplasmic retic- occurs after the zygote stage, affected ulum into the cytoplasm. The Ca 2+ subsequently individuals are a mosaic and different patterns affects cell metabolism by binding to the protein of tissue involvement may be seen between calmodulin. individuals • Pseudohypoparathyroidism: inactivating germline mutations in Gs result in Receptor tyrosine kinases pseudohypoparathyroidism type 1A if maternally inherited, with dysmorphic features (including The insulin, GH, prolactin and growth factor recep- short fourth or fifth metacarpal) and resistance to tors do not use second messengers. The receptors a variety of hormones that act via cAMP themselves can act as enzymes that phosphorylate (including parathyroid hormone, TSH and (‘kinase activity’) other proteins when hormone is gonadotrophins). Spontaneously occurring or bound at the cell surface. This is followed by a paternally inherited mutations cause the cascade of proteins phosphorylating other proteins dysmorphic features alone (pseudo- until gene transcription in the nucleus is modulated. 110 Endocrinology 4.1.3 Hormones that act hormone (TRH), TSH and L-thyroxine/L-triiodothyro- intracellularly nine (T4/T3). It is orchestrated by the hypothalamus, not by the end-organs. Hormones involved in the Steroids, vitamin D and thyroxine are sufficiently stress response may rise. lipid-soluble that they do not need cell surface receptors but can diffuse directly through the cell Hormones that fall membrane. They then bind to receptors in the cytoplasm, which results in shedding of heat shock • TSH, T4/T3a proteins that protect the empty receptor. The hor- • mone–receptor complex migrates into the nucleus LH, FSH • Testosterone, oestrogen where it alters the transcription of a large number of • genes (see Figure 14.6 in Chapter 14, Molecular Insulin (starvation) Medicine). May rise (stress hormones) 4.1.4 Hormone resistance syndromes • GH (though IGF-1 falls) • ACTH, glucocorticoids The following are conditions of hormone resistance • Adrenaline with the site of the defect shown. • Glucagon (starvation) • Prolactin • Receptor defect (hormone involved) a • Laron’s dwarfism (GH) In this case conversion of T4 to T3 is inhibited so T3 • Leprechaunism (Donahue’s syndrome, falls more than T4 ACTH, adrenocorticotrophic hormone; FSH, follicle- Rabson–Mendenhall syndrome [insulin]) stimulating hormone; GH, growth hormone; IGF-1, • Nephrogenic diabetes insipidus insulin-like growth factor 1; LH, luteinising hormone; (antidiuretic hormone [ADH]) T3, L-triiodothyronine; T4, L-thyroxine; TSH, thyroid- • Androgen resistance (testicular stimulating hormone.
Load more

Recommended publications
  • DIAGMOL Town, ZIPCODE :…………………………………………………… Director : Prof
    Mr. Mrs. (IN UPPER CASE, please) Name:……………………………………………………. Maiden Name:……………………………………. DMGL / Service de Médecine Génétique Centre d’accueil des prélèvements (CAP) First name :………………………………………………… Bâtiment des Laboratoires (BATLab), local 8D-0-850.1 Date of birth : ............ / ........... / …………… 4 rue Gabrielle-Perret-Gentil, 1211 Genève 14 Legal representative (for minors) : father mother Molecular and Genomic Diagnostics Laboratory Name/first name :…………………………………………… Street/N°:……………………………………………………… http://www.hug-ge.ch/feuilles-de-demande DIAGMOL Town, ZIPCODE :…………………………………………………… Director : Prof. Stylianos ANTONARAKIS Hospitalisation Unit: …………… Physician :…………………… Lab managers: N° EdS : …………………………………………………………… Dr J.-L. BLOUIN, Dr Th. NOUSPIKEL, Dr. M. GUIPPONI Invoice address: Patient Prescriptor Insurance [email protected], [email protected], [email protected] Type of case : Disease AI Accident Pregnancy Lab direct or results: Phone/FAX: +41 (0) 22 37 21 826 / 21 860 N° AVS (Mandatory for AI) : ………………………...................... Sample Entrance Center (CAP) : Phone +41 (0) 22 37 21 800 Insurance : ………………… Insured N° : ……………………… PHYSICIAN PHYSICIAN (NAME/First name - Street/N°- Town, ZIPCODE - Phone/FAX. IN UPPER CASES, PLEASE) COPY TO OTHER PHYSICIAN (NAME/First name - Street/N°- Town, ZIPCODE - Phone/FAX. IN UPPER CASES, PLEASE) « The laboratory is granted permission by the Physician/Patient to transmit copies of the report to other physicians» Opposition of the patient to the registration of this request results in the electronic patient record (DPI) of the HUG If the patient belongs to a family already known to the laboratory, please indicate index case NAME: CLINICAL INFORMATIONS given by the physician: Ethnic origins Father Mother Currently pregnant Date of last menses Number of weeks of amenorrhea SAMPLE(S) Most of our tests work from 4 ml of blood in EDTA (children <2 ans : 1 On every and single NAME First name ml : ok) or from purified DNA (some exceptions apply for some tests) tube.
    [Show full text]
  • Abstracts from the 9Th Biennial Scientific Meeting of The
    International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):15 DOI 10.1186/s13633-017-0054-x MEETING ABSTRACTS Open Access Abstracts from the 9th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society (APPES) and the 50th Annual Meeting of the Japanese Society for Pediatric Endocrinology (JSPE) Tokyo, Japan. 17-20 November 2016 Published: 28 Dec 2017 PS1 Heritable forms of primary bone fragility in children typically lead to Fat fate and disease - from science to global policy a clinical diagnosis of either osteogenesis imperfecta (OI) or juvenile Peter Gluckman osteoporosis (JO). OI is usually caused by dominant mutations affect- Office of Chief Science Advsor to the Prime Minister ing one of the two genes that code for two collagen type I, but a re- International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):PS1 cessive form of OI is present in 5-10% of individuals with a clinical diagnosis of OI. Most of the involved genes code for proteins that Attempts to deal with the obesity epidemic based solely on adult be- play a role in the processing of collagen type I protein (BMP1, havioural change have been rather disappointing. Indeed the evidence CREB3L1, CRTAP, LEPRE1, P4HB, PPIB, FKBP10, PLOD2, SERPINF1, that biological, developmental and contextual factors are operating SERPINH1, SEC24D, SPARC, from the earliest stages in development and indeed across generations TMEM38B), or interfere with osteoblast function (SP7, WNT1). Specific is compelling. The marked individual differences in the sensitivity to the phenotypes are caused by mutations in SERPINF1 (recessive OI type obesogenic environment need to be understood at both the individual VI), P4HB (Cole-Carpenter syndrome) and SEC24D (‘Cole-Carpenter and population level.
    [Show full text]
  • Genes in Eyecare Geneseyedoc 3 W.M
    Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease.
    [Show full text]
  • Homozygous Hypomorphic HNF1A Alleles Are a Novel Cause of Young-Onset Diabetes and Result in Sulphonylurea-Sensitive Diabetes
    Diabetes Care 1 Shivani Misra,1 Neelam Hassanali,2 Homozygous Hypomorphic Amanda J. Bennett,2 Agata Juszczak,2 Richard Caswell,3 Kevin Colclough,3 HNF1A Alleles Are a Novel Cause Jonathan Valabhji,4 Sian Ellard,3 of Young-Onset Diabetes and Nicholas S. Oliver,1,4 and Anna L. Gloyn2,5,6 Result in Sulphonylurea-Sensitive Diabetes https://doi.org/10.2337/dc19-1843 OBJECTIVE Heterozygous loss-of-function mutations in HNF1A cause maturity-onset diabetes of the young (MODY). Affected individuals can be treated with low-dose sulpho- nylureas. Individuals with homozygous HNF1A mutations causing MODY have not been reported. RESEARCH DESIGN AND METHODS We phenotyped a kindred with young-onset diabetes and performed molecular genetic testing, a mixed meal tolerance test, a sulphonylurea challenge, and in vitro assays to assess variant protein function. RESULTS A homozygous HNF1A variant (p.A251T) was identified in three insulin-treated 1 family members diagnosed with diabetes before 20 years of age. Those with the Diabetes, Endocrinology and Metabolism, Im- NOVEL COMMUNICATIONS IN DIABETES homozygous variant had low hs-CRP levels (0.2–0.8 mg/L), and those tested dem- perial College London, London, U.K. 2Oxford Centre for Diabetes, Endocrinology and onstrated sensitivity to sulphonylurea given at a low dose, completely transitioning off Metabolism, University of Oxford, Oxford, U.K. insulin. In silico modeling predicted a variant of unknown significance; however, in vitro 3Institute of Biomedical and Clinical Science, Uni- studies supported a modest reduction in transactivation potential (79% of that for the versity of Exeter Medical School, Exeter, U.K.
    [Show full text]
  • Abstracts from the 50Th European Society of Human Genetics Conference: Electronic Posters
    European Journal of Human Genetics (2019) 26:820–1023 https://doi.org/10.1038/s41431-018-0248-6 ABSTRACT Abstracts from the 50th European Society of Human Genetics Conference: Electronic Posters Copenhagen, Denmark, May 27–30, 2017 Published online: 1 October 2018 © European Society of Human Genetics 2018 The ESHG 2017 marks the 50th Anniversary of the first ESHG Conference which took place in Copenhagen in 1967. Additional information about the event may be found on the conference website: https://2017.eshg.org/ Sponsorship: Publication of this supplement is sponsored by the European Society of Human Genetics. All authors were asked to address any potential bias in their abstract and to declare any competing financial interests. These disclosures are listed at the end of each abstract. Contributions of up to EUR 10 000 (ten thousand euros, or equivalent value in kind) per year per company are considered "modest". Contributions above EUR 10 000 per year are considered "significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal and fetal echocardiography. The molecular karyotyping Genetics revealed a gain in 8p11.22-p23.1 region with a size of 27.2 Mb containing 122 OMIM gene and a loss in 8p23.1- E-P01.02 p23.3 region with a size of 6.8 Mb containing 15 OMIM Prenatal diagnosis in a case of 8p inverted gene. The findings were correlated with 8p inverted dupli- duplication deletion syndrome cation deletion syndrome. Conclusion: Our study empha- sizes the importance of using additional molecular O¨. Kırbıyık, K. M. Erdog˘an, O¨.O¨zer Kaya, B. O¨zyılmaz, cytogenetic methods in clinical follow-up of complex Y.
    [Show full text]
  • UNSCEAR 2001 Report to the General Assembly, with Scientific Annex
    HEREDITARY EFFECTS OF RADIATION United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2001 Report to the General Assembly, with Scientific Annex UNITED NATIONS HEREDITARY EFFECTS OF RADIATION United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2001 Report to the General Assembly, with Scientific Annex UNITED NATIONS New York, 2001 NOTE The report of the Committee without its scientific annex appears as Official Records of the General Assembly. Fifty-sixth Session, Supplement No. 46 (N56146). The designation employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the pad of the Secretariat of the United Nationsconcerning the legal status of any country, temtory, city orarea, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, In most cases, those that were in use at the time the data were collected or the text prepared. In othercases, however, the names have been updated, where this was posslble and appropriate, to reflect political changes. UNITED NATIONS PUBLICATION Sales No. E.O1 .IX.2 ISBN 92-1-1 42244-2 Report of the United Nations Scientific Committee on the Effects of Atomic Radiation to the General Assembly 1. During the past few years, the United Nations 4. The Committee wishes to acknowledge the assistance Scientific Committee on the Effects of Atomic Radiation1 of the consultant, K. Sankaranarayanan, in the preparation has undertaken broad reviews of the sources and effects of of the scientific annex and the advice of the international ionizing radiation.
    [Show full text]
  • Uncommon Forms of Diabetes
    Clinical Medicine 2021 Vol 21, No 4: e337–41 CME: DIABETES Uncommon forms of diabetes Authors: Yun-Ni LeeA and Mohammed SB HudaB Diabetes mellitus is a common condition which all clinicians and insulin independence. It is estimated to account for 1%–2% will encounter in their clinical practice. The most common of patients diagnosed with diabetes and, in the UK, the prevalence form is type 2 diabetes followed by type 1 diabetes. However, of MODY is estimated to be at 108 cases per million.3 However, there are many other atypical forms of diabetes which are it may be a significant underestimate and these figures are not important for a clinician to consider as it can impact on the accurate until large population screening studies are performed. ABSTRACT diagnosis and their management. The most common mutations are hepatocyte nuclear factor-1- This article focuses on maturity onset diabetes of the young alpha (HNF1α; 52%), glucokinase (GCK; 32%) and HNF4α (10%), (MODY), latent autoimmune diabetes in adults (LADA), see Table 2.3 ketosis-prone diabetes and other secondary forms of diabetes such as pancreatic cancer and haemochromatosis. We briefly Hepatocyte nuclear factor-1-alpha gene describe the key clinical features of these forms of diabetes and their investigations and treatment. Formerly called MODY3, mutations on the HNF1α gene on chromosome 3 are associated with a progressive defect of insulin secretion.4 Mutations here also result in low renal threshold for 5 Introduction glucose and thus mutation carriers have detectable glycosuria. In the UK, around 90% of people with diabetes have type 2 diabetes (T2D), around 8% have type 1 diabetes (T1D) and around 2% have other forms of diabetes.1 Key points Typically, we see T1D present in a young, lean patient with Suspect other uncommon forms of diabetes if the clinical marked symptoms of polyuria, polydipsia, weight loss and diabetic picture does not fit type 1 or type 2 diabetes.
    [Show full text]
  • Two MODY 2 Families Identified in Brazilian Subjects
    case report Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects Hiperglicemia incidental em crianças: duas famílias com MODY 2 identificadas em brasileiros Lílian A. Caetano1,2, Alexander A. L. Jorge1, Alexsandra C. Malaquias1, Ericka B. Trarbach1, Márcia S. Queiroz2, Márcia Nery2, Milena G. Teles1,2 SUMMARY Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode 1 Unidade de Endocrinologia of inheritance, early onset of hyperglycemia, and defects of insulin secretion. MODY subtypes Genética e Laboratório de described present genetic, metabolic, and clinical differences. MODY 2 is characterized by mild Endocrinologia Molecular e Celular/LIM25, Disciplina de asymptomatic fasting hyperglycemia, and rarely requires pharmacological treatment. Hence, Endocrinologia, Faculdade precise diagnosis of MODY is important for determining management and prognosis. We report de Medicina da Universidade two heterozygous GCK mutations identified during the investigation of short stature. Case 1: a de São Paulo (FMUSP), São Paulo, SP, Brazil prepubertal 14-year-old boy was evaluated for constitutional delay of growth and puberty. During 2 Unidade de Diabetes, follow-up, he showed abnormal fasting glucose (113 mg/dL), increased level of HbA1c (6.6%), and Hospital das Clínicas, FMUSP, negative β-cell antibodies. His father and two siblings also had slightly elevated blood glucose le- São Paulo, SP, Brazil vels. The mother had normal glycemia. A GCK heterozygous missense mutation, p.Arg191Trp, was identified in the proband. Eighteen family members were screened for this mutation, and 11 had the mutation in heterozygous state. Case 2: a 4-year-old boy investigated for short stature revealed no other laboratorial alterations than elevated glycemia (118 mg/dL); β-cell antibodies were nega- tive.
    [Show full text]
  • Genetic, Metabolic and Clinical Characteristics of Maturity Onset Diabetes of the Young
    European Journal of Endocrinology (1998) 138 233±239 ISSN 0804-4643 REVIEW Genetic, metabolic and clinical characteristics of maturity onset diabetes of the young Gilberto Velho and Philippe Froguel1 INSERM U-342, HoÃpital Saint Vincent de Paul, Paris, France and 1CNRS EP10, Institut Pasteur de Lille et CHU, Lille, France (Correspondence should be addressed to G Velho, INSERM U-342, HoÃpital Saint Vincent de Paul, 82 Avenue Denfert Rochereau, 75014 Paris, France) Abstract Maturity onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM) characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. To date, three MODY genes have been identi®ed on chromosomes 20q (MODY1/hepatic nuclear factor (HNF)-4a), 7p (MODY2/glucokinase) and 12q (MODY3/HNF-1a). Mutations in MODY2/glucokinase result in mild chronic hyperglycaemia as a result of reduced pancreatic beta-cell responsiveness to glucose, and decreased net accumulation of hepatic glycogen and increased hepatic gluconeogenesis after meals. In contrast, MODY1 and MODY3 are characterised by severe insulin secretory defects, and by major hyperglycaemia associated with microvascular complications. The role of the three known MODY genes in susceptibility to the more common late-onset NIDDM remain uncertain. Genetic studies seem to exclude a role as major susceptibility genes, but leave unresolved whether they may have a minor role in a polygenic context or an important role in particular populations. European Journal of Endocrinology 138 233±239 MODY is a monogenic form of NIDDM MODY3/HNF-1a (11, 12) respectively, can cause this form of diabetes.
    [Show full text]
  • Mat Kadi Tora Tutti O Al Ut Hit Hitta Atuh
    MAT KADI TORA TUTTI USO AL20180235194A1 UT HIT HITTA ATUH ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0235194 A1 Fahrenkrug et al. (43 ) Pub . Date : Aug . 23, 2018 ( 54 ) MULTIPLEX GENE EDITING Publication Classification (51 ) Int. Ci. ( 71 ) Applicant: Recombinetics , Inc ., Saint Paul, MN A01K 67/ 027 (2006 . 01 ) (US ) C12N 15 / 90 ( 2006 .01 ) (72 ) Inventors : Scott C . Fahrenkrug, Minneapolis , (52 ) U . S . CI. MN (US ) ; Daniel F . Carlson , CPC .. .. A01K 67 / 0276 (2013 . 01 ) ; C12N 15 / 907 Woodbury , MN (US ) ( 2013 .01 ) ; A01K 67 /0275 ( 2013 .01 ) ; A01K 2267/ 02 (2013 .01 ) ; AOIK 2217 / 15 (2013 .01 ) ; AOIK 2227 / 108 ( 2013 .01 ) ; AOIK 2217 /07 (21 ) Appl. No. : 15 /923 , 951 ( 2013 .01 ) ; A01K 2227/ 101 (2013 .01 ) ; AOIK ( 22 ) Filed : Mar. 16 , 2018 2217 /075 ( 2013 .01 ) (57 ) ABSTRACT Related U . S . Application Data Materials and methods for making multiplex gene edits in (62 ) Division of application No . 14 /698 ,561 , filed on Apr. cells and are presented . Further methods include animals 28 , 2015, now abandoned . and methods of making the same . Methods of making ( 60 ) Provisional application No . 61/ 985, 327, filed on Apr. chimeric animals are presented , as well as chimeric animals . 28 , 2014 . Specification includes a Sequence Listing . Patent Application Publication Aug . 23 , 2018 Sheet 1 of 13 US 2018 / 0235194 A1 GENERATION OF HOMOZYGOUS CATTLE EDITED AT ONE ALLELE USING SINGLE EDITS Edit allele , Raise FO to Mate FO enough times Raise F1s to Mate F1 siblings Clone cell , sexual maturity , to produce enough F1 sexualmaturity , to make Implant, Gestate 2 years generation carrying 2 years homozygous KO , 9 months , birth edited allele to mate 9 months of FO with each other Generation Primary Fibroblasts ? ? ? Time, years FIG .
    [Show full text]
  • Endocrine Genetic Test List
    Endocrine Genetic Test List Associated conditions Test No. Test Name Genes Included and phenotypes Bone HPP, X-Linked Hypophosphatemia, X-Linked Hypophosphatemic Rickets, XLH, Hypophosphatemic Rickets, X-Linked Hypophosphatasia and Dominant Hypophosphatemic Rickets (XLHR), ALPL, CLCN5, CYP2R1, CYP27B1, DMP1, ENPP1, FGF23, PHEX, 630292 Hypophosphatemic Rickets X-Linked Rickets (XLR), Vitamin D-Resistant SLC34A3, VDR Panel Rickets, X-Linked Vitamin D-Resistant Rickets (VDRR), Hypophosphatemic Vitamin D-Resistant Rickets (HPDR), Phosphate Diabetes, Familial Hypophosphatemic Rickets BMP1, COL1A1, COL1A2, CREB3L1, CRTAP, FKBP10, IFITM5, LRP5, Osteogenesis Imperfecta 630543 MBTPS2, P3H1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, SPARC, OI, Juvenile Primary Osteoporosis Genetic Panel TENT5A, TMEM38B, WNT1 Cancer Familial Isolated Hyperparathyroidism, VistaSeq® Endocrine Cancer CDC73, MAX, MEN1, NF1, PRKAR1A, PTEN, RET, SDHB, SDHC, SDHD, 481374 Multiple Endocrine Neoplasia, Paraganglioma, Panel* TMEM127, TP53 and VHL Parathyroid Cancer, Pheochromocytoma Diabetes and Insulin Maturity-Onset Diabetes of the 630568 GCK, HNF1A, HNF1B, HNF4A Young (MODY) 4-gene Panel Maturity-Onset Diabetes of ABCC8, APPL1, BLK, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11, 630513 the Young (MODY) Expanded KLF11, NEUROD1, PAX4, PDX1 Genetic Panel Congenital Hyperinsulinism ABCC8, GCK, GLUD1, HADH, HNF1A, HNF4A, KCNJ11, PGM1, PMM2, 630500 Hypoglycemia Genetic Panel SLC16A1, UCP2 Growth and Development Combined Pituitary Hormone GLI1, HESX1, LHX3, LHX4, OTX2, POU1F1, PROKR2, PROP1,
    [Show full text]
  • An Interesting Case of Young Onset Diabetes Mellitus
    International Journal of Research in Medical Sciences Gulati S et al. Int J Res Med Sci. 2017 Sep;5(9):4178-4180 www.msjonline.org pISSN 2320-6071 | eISSN 2320-6012 DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20174007 Case Report An interesting case of young onset diabetes mellitus Shipra Gulati*, Tanvi Batra, Akshay A. Dhamne, Vijayashree S. Gokhale Department of Medicine, Dr. DY Patil Medical College and Hospital, Pimpri, Pune, Maharashtra, India Received: 23 June 2017 Accepted: 22 July 2017 *Correspondence: Dr. Shipra Gulati, E-mail: [email protected] Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT A 24 years old female, was admitted with symptoms of urinary tract infection. She was married and had bad obstetric history. She was known diabetic for 16 years of age and was on regular treatment with injection human insulin mixtard since the time of diagnosis, but had no episode of diabetic ketosis/ ketoacidosis. She had a positive family history of diabetes. She was further evaluated and was found to have normal C peptide levels and islet cell antibodies were found to be negative. Hence, the possibility of MODY (monogenic diabetes) was considered. Her genetic testing could not be done due to financial constraints. But a trial of sulfonylureas was given along with reduction in the dose of insulin to which she responded well and is presently well controlled.
    [Show full text]