DOCSLIB.ORG

Laboratory Diagnosis of Galactosemia: a Technical Standard and Guideline of the American College of Medical Genetics and Genomics (ACMG)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Laboratory Diagnosis of Galactosemia: a Technical Standard and Guideline of the American College of Medical Genetics and Genomics (ACMG) © American College of Medical Genetics and Genomics ACMG STANDARDS AND GUIDELINES Laboratory diagnosis of galactosemia: a technical standard and guideline of the American College of Medical Genetics and Genomics (ACMG) Marzia Pasquali, PhD1, Chunli Yu, MD2 and Bradford Coffee, PhD3; on behalf of the ACMG Laboratory Quality Assurance Committee Disclaimer: These ACMG Standards and Guidelines are developed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these Standards and Guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient’s record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures. Galactosemias are inherited disorders of galactose metabolism deficiency and UDP-galactose-4′-epimerase deficiency is not due to deficiency in one of the three enzymes involved in the Leloir universal. Early identification and treatment of galactosemia pathway: galactose-1-phosphate uridyltransferase, galactokinase, leads to improved outcome. This document reviews the and uridine diphosphate (UDP)-galactose-4′-epimerase. laboratory methods and best practices for the diagnosis of Galactose-1-phosphate uridyltransferase deficiency, or classic galactosemia. galactosemia, is the most frequent and the most severe of the three enzyme deficiencies; it is characterized by failure to Genet Med advance online publication 26 October 2017 thrive, liver failure, susceptibility to sepsis, and death, if untreated. Key Words: enzyme assay; galactokinase; galactose-1-phosphate Newborn screening for classic galactosemia has been implemented 0 in all of the United States, while screening for galactokinase uridyltransferase; galactosemia; UDP-galactose-4 -epimerase METHODS the literature provided conflicting evidence about a topic or This laboratory technical standard and guideline was when there was insufficient evidence, the authors used expert informed by a review of the literature, including any current opinion to inform the recommendations. Expert opinion guidelines, and expert opinion. Resources consulted included included the coauthors of the document, as well as any experts PubMed (search terms: galactosemia, galactose-1-phosphate consulted outside the workgroup and acknowledged in this uridyltransferase, galactokinase, galactose epimerase, galac- document. Any conflicts of interest for workgroup members tose-1-phosphate, Duarte variant), the American College or consultants are listed. The ACMG Laboratory Quality of Medical Genetics and Genomics (ACMG) Technical Assurance Committee (Lab QA) reviewed the document Standards and Guidelines for Clinical Genetics Laboratories, providing further input on the content, and a final draft was Clinical and Laboratory Standards Institute guidelines, CLIA delivered to the ACMG Board of Directors for review and regulations, and the Centers for Disease Control and approval to send out for member comment. The final draft of Prevention’s Morbidity and Mortality Weekly Report on Good the document was uploaded to the ACMG website and an Laboratory Practices for Biochemical Genetics Testing and e-mail link was sent to ACMG members inviting all to Newborn Screening for Inherited Metabolic Disorders. When provide comment. All members’ comments were assessed by 1University of Utah School of Medicine and ARUP Laboratories, Salt Lake City, Utah, USA; 2Mount Sinai Genetic Testing Laboratory, Icahn School of Medicine at Mount Sinai, New York, New York, USA; 3Myriad Genetics, Salt Lake City, Utah, USA. Correspondence: Marzia Pasquali ([email protected]) The Board of Directors of the American College of Medical Genetics and Genomics approved this guideline on 22 May 2017. Submitted 30 August 2017; accepted 30 August 2017; advance online publication 26 October 2017. doi:10.1038/gim.2017.172 GENETICS in MEDICINE | Volume 20 | Number 1 | January 2018 3 ACMG STANDARDS AND GUIDELINES PASQUALI et al | Laboratory diagnosis of galactosemia CO2 + Xylulose DIET Galactitol Galactonate Lactose galactose aldose dehydrogenase reductase NADP+ NADPH NADH NAD+ galactokinase (GALK) Galactose Gal-1-P Endogenous production ATP ADP UDPGlu galactose-1-phosphate uridyl transferase (GALT) Glu-1-P UDPGlu UDPGal uridine diphosphate galactose-4-epimerase (GALE) Figure 1 Metabolism of galactose. Galactose, deriving from diet and, in minor part, from endogenous synthesis, is phosphorylated to galactose-1- phosphate (Gal-1-P) by galactokinase, the first enzyme in the Leloir pathway. Uridine diphosphate (UDP)-galactose is produced from Gal-1-P and UDP- glucose through the enzyme galactose-1-phosphate uridyltransferase. UDP-galactose is then converted to UDP-glucose by the enzyme uridine diphosphate galactose-4-epimerase. UDP-glucose is recycled back into the pathway. the authors and additional evidence was included; our this referral source. Newborn screening for classic galactose- recommendations were amended as deemed appropriate. mia identifies patients with decreased GALT activity in dried Member comments and author responses were reviewed by a blood spots (DBS) and, for some states, elevated galactose representative of the Lab QA committee and the ACMG sugars. States including galactose sugars as part of their Board. The final document was approved by the ACMG screening also identify cases of GALK and GALE deficiencies, Board of Directors. while those relying only on galactose sugars alone may miss cases of GALT deficiency in patients on a galactose-limited OVERVIEW diet. Galactosemia testing may also be initiated by a positive Galactosemia encompasses three distinct enzymatic deficien- family history, or by nonspecific features of the disease in an cies in the Leloir pathway of galactose metabolism (Figure 1). older patient. Although diagnostic testing is relatively This pathway plays a critical role in converting D-galactose straightforward, significant variability can result from pre- to glucose-1-phoshate for entry into glycolysis, as well as analytic and analytic influences if not properly controlled. supplying uridine diphosphate galactose (UDP-galactose) for These guidelines were developed to delineate best practices for the galactosylation of carbohydrates and lipids. Classic enzyme and metabolite testing for galactosemia and to galactosemia (MIM 230400) is caused by deficient galactose- characterize variables that can influence test performance 1-phosphate uridyltransferase (GALT) activity, leading to and results interpretation. elevated galactose-1-phosphate (Gal-1-P) and other galactose metabolites in blood and urine. A variant form of galacto- semia, referred to as Duarte variant or DG galactosemia, is BACKGROUND characterized by approximately 25% of normal GALT activity Biochemical and molecular characteristics of galactose- and may be clinically benign.1 Galactokinase (GALK) metabolizing enzymes deficiency and UDP-galactose-4′-epimerase (GALE) defi- Galactose-1-phosphate uridyltransferase ciency are clinically and biochemically distinct from classic Galactose-1-phosphate uridyltransferase (GALT; EC 2.7.7.12), galactosemia. For each of these conditions, the diagnosis is the second enzyme of the Leloir pathway, is a member of the based on the demonstration of severely reduced or absent histidine triad superfamily and is a homodimer composed of enzyme activity in red blood cells (RBCs). DNA analysis of two 43-kDa subunits.2 This enzyme catalyzes the interconver- the GALT, GALK1,orGALE genes is often performed as part sion of Gal-1-P to glucose-1-phosphate, with the concomitant of the diagnostic evaluation. interconversion of the co-substrate UDP-glucose to UDP- Because galactosemia is included in all newborn screening galactose. The reaction follows a “ping-pong” mechanism programs in the United States and many other countries whereby histidine at the active site reacts with UDP-glucose worldwide, the majority of diagnostic testing originates from loading the enzyme with uridine 5′-monophosphate (UMP); 4 Volume 20 | Number 1 | January 2018 | GENETICS in MEDICINE Laboratory diagnosis of galactosemia | PASQUALI et al ACMG STANDARDS AND GUIDELINES UMP then reacts with galactose-1-phosphate, forming the Gal-1-P.14 It is encoded by GALK1, a gene spanning 8 exons final product, UDP-galactose.3 and 7.3 kb on chromosome 17q25.1.15 Deficiency of GALK The GALT gene encompasses 11 exons spanning 4.3 kb of results in type II galactosemia or galactokinase deficiency chromosome 9p13. An open-access database has curated (MIM 230200). Several GALK pathogenic variants have been more than 250 pathogenic variants including
Load more

Recommended publications
  • Molecular Characterization of Galactokinase Deficiency In
    J Hum Genet (1999) 44:377–382 © Jpn Soc Hum Genet and Springer-Verlag 1999377 ORIGINAL ARTICLE Minoru Asada · Yoshiyuki Okano · Takuji Imamura Itsujin Suyama · Yutaka Hase · Gen Isshiki Molecular characterization of galactokinase deficiency in Japanese patients Received: May 19, 1999 / Accepted: August 21, 1999 Abstract Galactokinase (GALK) deficiency is an autoso- Key words Galactosemia · Galactokinase (GALK) · Muta- mal recessive disorder, which causes cataract formation in tion · Genotype · Phenotype children not maintained on a lactose-free diet. We charac- terized the human GALK gene by screening a Japanese genomic DNA phage library, and found that several nucle- otides in the 59-untranslated region and introns 1, 2, and 5 in Introduction our GALK genomic analysis differed from published data. A 20-bp tandem repeat was found in three places in intron Galactokinase (GALK: McKUSICK 230200) is the first 5, which were considered insertion sequences. We identified enzyme in the Leloir pathway of galactose metabolism; it five novel mutations in seven unrelated Japanese patients catalyzes the phosphorylation of galactose to galactose- with GALK deficiency. There were three missense muta- 1-phosphate. GALK deficiency, first described in 1965 tions and two deletions. All three missense mutations (Gitzelmann 1965), is an autosomal recessive genetic disor- (R256W, T344M, and G349S) occurred at CpG dinucle- der with an incidence of 1/1,000,000 in Japan (Aoki and otides, and the T344M and G349S mutations occurred in Wada 1988) on newborn mass screening and an incidence of the conserved region. The three missense mutations led to a 1/1,000,000 in Caucasians (Segal and Berry 1995).
    [Show full text]
  • Clinical Applications and Implications of Common and Founder Mutations in Indian Subpopulations
    REVIEW OFFICIAL JOURNAL Clinical Applications and Implications of Common and Founder Mutations in Indian Subpopulations www.hgvs.org Arunkanth Ankala,1∗ † Parag M. Tamhankar,2 † C. Alexander Valencia,3,4 Krishna K. Rayam,5 Manisha M. Kumar,5 and Madhuri R. Hegde1 1Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia; 2ICMR Genetic Research Center, National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India; 3Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; 4Department of Pediatrics, University of Cincinnati Medical School, Cincinnati, Ohio; 5Department of Biosciences, CMR Institute of Management Studies, Bangalore, Karnataka, India Communicated by Arupa Ganguly Received 24 October 2013; accepted revised manuscript 16 September 2014. Published online 27 November 2014 in Wiley Online Library (www.wiley.com/humanmutation). DOI: 10.1002/humu.22704 that include a lack of widespread awareness about genetic disorders in the general population and the scarcity of specialized medical ABSTRACT: South Asian Indians represent a sixth of the world’s population and are a racially, geographically, and professionals and affordable genetic tests. Seeking a molecular di- genetically diverse people. Their unique anthropological agnosis and understanding the risk estimates are critical to making structure, prevailing caste system, and ancient religious sound reproductive choices, especially in families with an affected practices have all impacted the genetic composition of most individual. Adding to this adversity is the absence of a properly func- of the current-day Indian population. With the evolving tioning social health care system and insufficient encouragement socio-religious and economic activities of the subsects and of individual health insurance by the government.
    [Show full text]
  • Gene Symbol Gene Description ACVR1B Activin a Receptor, Type IB
    Table S1. Kinase clones included in human kinase cDNA library for yeast two-hybrid screening Gene Symbol Gene Description ACVR1B activin A receptor, type IB ADCK2 aarF domain containing kinase 2 ADCK4 aarF domain containing kinase 4 AGK multiple substrate lipid kinase;MULK AK1 adenylate kinase 1 AK3 adenylate kinase 3 like 1 AK3L1 adenylate kinase 3 ALDH18A1 aldehyde dehydrogenase 18 family, member A1;ALDH18A1 ALK anaplastic lymphoma kinase (Ki-1) ALPK1 alpha-kinase 1 ALPK2 alpha-kinase 2 AMHR2 anti-Mullerian hormone receptor, type II ARAF v-raf murine sarcoma 3611 viral oncogene homolog 1 ARSG arylsulfatase G;ARSG AURKB aurora kinase B AURKC aurora kinase C BCKDK branched chain alpha-ketoacid dehydrogenase kinase BMPR1A bone morphogenetic protein receptor, type IA BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) BRAF v-raf murine sarcoma viral oncogene homolog B1 BRD3 bromodomain containing 3 BRD4 bromodomain containing 4 BTK Bruton agammaglobulinemia tyrosine kinase BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) C9orf98 chromosome 9 open reading frame 98;C9orf98 CABC1 chaperone, ABC1 activity of bc1 complex like (S. pombe) CALM1 calmodulin 1 (phosphorylase kinase, delta) CALM2 calmodulin 2 (phosphorylase kinase, delta) CALM3 calmodulin 3 (phosphorylase kinase, delta) CAMK1 calcium/calmodulin-dependent protein kinase I CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha CAMK2B calcium/calmodulin-dependent
    [Show full text]
  • Incidence of Inborn Errors of Metabolism by Expanded Newborn
    Original Article Journal of Inborn Errors of Metabolism & Screening 2016, Volume 4: 1–8 Incidence of Inborn Errors of Metabolism ª The Author(s) 2016 DOI: 10.1177/2326409816669027 by Expanded Newborn Screening iem.sagepub.com in a Mexican Hospital Consuelo Cantu´-Reyna, MD1,2, Luis Manuel Zepeda, MD1,2, Rene´ Montemayor, MD3, Santiago Benavides, MD3, Hector´ Javier Gonza´lez, MD3, Mercedes Va´zquez-Cantu´,BS1,4, and Hector´ Cruz-Camino, BS1,5 Abstract Newborn screening for the detection of inborn errors of metabolism (IEM), endocrinopathies, hemoglobinopathies, and other disorders is a public health initiative aimed at identifying specific diseases in a timely manner. Mexico initiated newborn screening in 1973, but the national incidence of this group of diseases is unknown or uncertain due to the lack of large sample sizes of expanded newborn screening (ENS) programs and lack of related publications. The incidence of a specific group of IEM, endocrinopathies, hemoglobinopathies, and other disorders in newborns was obtained from a Mexican hospital. These newborns were part of a comprehensive ENS program at Ginequito (a private hospital in Mexico), from January 2012 to August 2014. The retrospective study included the examination of 10 000 newborns’ results obtained from the ENS program (comprising the possible detection of more than 50 screened disorders). The findings were the following: 34 newborns were confirmed with an IEM, endocrinopathies, hemoglobinopathies, or other disorders and 68 were identified as carriers. Consequently, the estimated global incidence for those disorders was 3.4 in 1000 newborns; and the carrier prevalence was 6.8 in 1000. Moreover, a 0.04% false-positive rate was unveiled as soon as diagnostic testing revealed negative results.
    [Show full text]
  • Hereditary Galactokinase Deficiency J
    Arch Dis Child: first published as 10.1136/adc.46.248.465 on 1 August 1971. Downloaded from Alrchives of Disease in Childhood, 1971, 46, 465. Hereditary Galactokinase Deficiency J. G. H. COOK, N. A. DON, and TREVOR P. MANN From the Royal Alexandra Hospital for Sick Children, Brighton, Sussex Cook, J. G. H., Don, N. A., and Mann, T. P. (1971). Archives of Disease in Childhood, 46, 465. Hereditary galactokinase deficiency. A baby with galactokinase deficiency, a recessive inborn error of galactose metabolism, is des- cribed. The case is exceptional in that there was no evidence of gypsy blood in the family concerned. The investigation of neonatal hyperbilirubinaemia led to the discovery of galactosuria. As noted by others, the paucity of presenting features makes early diagnosis difficult, and detection by biochemical screening seems desirable. Cataract formation, of early onset, appears to be the only severe persisting complication and may be due to the biosynthesis and accumulation of galactitol in the lens. Ophthalmic surgeons need to be aware of this enzyme defect, because with early diagnosis and dietary treatment these lens changes should be reversible. Galactokinase catalyses the conversion of galac- and galactose diabetes had been made in this tose to galactose-l-phosphate, the first of three patient (Fanconi, 1933). In adulthood he was steps in the pathway by which galactose is converted found to have glycosuria as well as galactosuria, and copyright. to glucose (Fig.). an unexpectedly high level of urinary galactitol was detected. He was of average intelligence, and his handicaps, apart from poor vision, appeared to be (1) Galactose Gackinase Galactose-I-phosphate due to neurofibromatosis.
    [Show full text]
  • The Counsyl Foresight™ Carrier Screen
    The Counsyl Foresight™ Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.counsyl.com | [email protected] | (888) COUNSYL The Counsyl Foresight Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia .................................................................................................................................................................................... 8 21-hydroxylase-deficient Congenital Adrenal Hyperplasia ...........................................................................................................................................................................................10 6-pyruvoyl-tetrahydropterin Synthase Deficiency ..........................................................................................................................................................................................................12 ABCC8-related Hyperinsulinism........................................................................................................................................................................................................................................ 14 Adenosine Deaminase Deficiency .................................................................................................................................................................................................................................... 16 Alpha Thalassemia.............................................................................................................................................................................................................................................................
    [Show full text]
  • Induction of Uridyl Transferase Mrna-And Dependency on GAL4 Gene Function (In Vitro Translation/Immunoprecipitation/GAL Gene Cluster/Positive Regulation) JAMES E
    Proc. Nati. Acad. Sci. USA Vol. 75, No. 6, pp. 2878-2882, June 1978 Genetics Regulation of the galactose pathway in Saccharomyces cerevisiae: Induction of uridyl transferase mRNA-and dependency on GAL4 gene function (in vitro translation/immunoprecipitation/GAL gene cluster/positive regulation) JAMES E. HOPPER*, JAMES R. BROACHt, AND LUCY B. ROWE* * Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02154; and t Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 Communicated by Norman H. Giles, April 10,1978 ABSTRACT In Saccharomyces cerevisiae, utilization of Genetic control of the inducible galactose pathway enzymes galactose requires four inducible enzyme activities. Three of involves the four structural genes GALI, GAL10, GAL7, and these activities (galactose-l-phosphate uridyl transferase, EC genes, GAL4, GAL81 (c), GAL80 2.7.7.10; uridine diphosphogalactose 4-epimerase, EC 5.1.3.2; GAL2 and four regulatory and galactokinase, EC 2.7.1.6) are specified by three tightly (i), and GALS.* Mutations in GALl, GAL10, GAL7, and GAL2 linked genes (GAL7, GALlO, and GALI, respectively) on chro- affect the individual appearance of galactokinase, epimerase, mosome II, whereas the fourth, galactose transport, is specified transferase, and galactose transport activities, respectively (6). by a gene (GALS) located on chromosome XIL Although classic Mutations defining the GALl, GAL10, and GAL7 genes have genetic analysis has revealed both positive and negative regu- invariably been recessive, and they map in three tightly linked latory genes that coordinately affect the appearance of ail four complementation groups near the centromere of chromosome enzyme activities, neither the basic events leading to the ap- pearance of enzyme activities nor the roles of the regulatory II (6, 9, 10).
    [Show full text]
  • Screening for Galactosemia: Is There a Place for It?
    International Journal of General Medicine Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Screening for galactosemia: is there a place for it? This article was published in the following Dove Press journal: International Journal of General Medicine Magd A Kotb Abstract: Galactose is a hexose essential for production of energy, which has a prebiotic Lobna Mansour role and is essential for galactosylation of endogenous and exogenous proteins, cera- Radwa A Shamma mides, myelin sheath metabolism and others. The inability to metabolize galactose results in galactosemia. Galactosemia is an autosomal recessive disorder that affects newborns Pediatrics Department, Faculty of Medicine, Kasr Al Ainy, Cairo University, who are born asymptomatic, apparently well and healthy, then develop serious morbidity Cairo, Egypt and mortality upon consuming milk that contains galactose. Those with galactosemia have a deficiency of an enzyme: classic galactosemia (type 1) results from severe deficiency of galactose-1-uridylyltransferase, while galactosemia type II results from galactokinase deficiency and type III results from galactose epimerase deficiency. Many countries include neonatal screening for galactosemia in their national newborn screening program; however, others do not, as the condition is rather rare, with an incidence of 1:30,000–1:100,000, and screening may be seen as not cost-effective and logistically demanding. Early detection and intervention by restricting galactose is not curative but is very rewarding, as it prevents deaths, mental retardation, liver cell failure, renal tubular acidosis and neurological sequelae, and may lead to resolution of cataract formation. Hence, national newborn screening for galactosemia prevents serious potential life-long suffering, morbidity and mortality.
    [Show full text]
  • Supplementary Materials
    Supplementary Materials Figure S1. Differentially abundant spots between the mid-log phase cells grown on xylan or xylose. Red and blue circles denote spots with increased and decreased abundance respectively in the xylan growth condition. The identities of the circled spots are summarized in Table 3. Figure S2. Differentially abundant spots between the stationary phase cells grown on xylan or xylose. Red and blue circles denote spots with increased and decreased abundance respectively in the xylan growth condition. The identities of the circled spots are summarized in Table 4. S2 Table S1. Summary of the non-polysaccharide degrading proteins identified in the B. proteoclasticus cytosol by 2DE/MALDI-TOF. Protein Locus Location Score pI kDa Pep. Cov. Amino Acid Biosynthesis Acetylornithine aminotransferase, ArgD Bpr_I1809 C 1.7 × 10−4 5.1 43.9 11 34% Aspartate/tyrosine/aromatic aminotransferase Bpr_I2631 C 3.0 × 10−14 4.7 43.8 15 46% Aspartate-semialdehyde dehydrogenase, Asd Bpr_I1664 C 7.6 × 10−18 5.5 40.1 17 50% Branched-chain amino acid aminotransferase, IlvE Bpr_I1650 C 2.4 × 10−12 5.2 39.2 13 32% Cysteine synthase, CysK Bpr_I1089 C 1.9 × 10−13 5.0 32.3 18 72% Diaminopimelate dehydrogenase Bpr_I0298 C 9.6 × 10−16 5.6 35.8 16 49% Dihydrodipicolinate reductase, DapB Bpr_I2453 C 2.7 × 10−6 4.9 27.0 9 46% Glu/Leu/Phe/Val dehydrogenase Bpr_I2129 C 1.2 × 10−30 5.4 48.6 31 64% Imidazole glycerol phosphate synthase Bpr_I1240 C 8.0 × 10−3 4.7 22.5 8 44% glutamine amidotransferase subunit Ketol-acid reductoisomerase, IlvC Bpr_I1657 C 3.8 × 10−16
    [Show full text]
  • Galactosemia
    Galactosemia Classic galactosemia (G/G) is an autosomal recessive disor- ii. Compound heterozygotes (D/G or N314D/Q188R) der of galactose metabolism, caused by a deficiency of galac- a) Relatively benign in most infants tose-L-phosphate uridyl transferase. The incidence is estimated b) May or may not require dietary intervention to be 1 in 30,000 births, based on the results of newborn c. Los Angels (LA) variant with identical N314D mis- screening programs. sense mutation but has normal erythrocyte GALT activity GENETICS/BASIC DEFECTS d. S135L allele 1. Inheritance: autosomal recessive i. Prevalent in Africa 2. Cause: deficiency of galactose-L-phosphate uridyl ii. A good prognosis if therapy is initiated in the transferase (GALT) neonatal period without neonatal hepatotoxicity 3. Galactose-L-phosphate uridyl transferase and chronic problems a. The gene for GALT is mapped on chromosome 9p13 e. K285N allele b. GALT is second enzyme in the Leloir pathway, cat- i. Prevalent in Southern Germany, Austria, and alyzing conversion of galactose-L-phosphate and UDP Croatia glucose to UDP galactose and glucose-L-phosphate ii. A poor prognosis for neurological and cognitive c. Essential in human infants who consume lactose as dysfunction in either the homozygous state or their primary carbohydrate source compound heterozygous state with Q188R d. Near total absence of GALT activity in infants with classical galactosemia CLINICAL FEATURES e. A deficiency causes elevated levels of galactose- L-phosphate and galactitol in body tissues 1. Onset of symptoms 4. Endogenous production of galactose may be responsible a. May present by the end of the first week of life for the long-term effects, such as cognitive dysfunction b.
    [Show full text]
  • Iowa Newborn Screening Program Annual Report
    Fiscal Year 2016 Blood Spot Newborn Screening Follow Up Report Short Term and Long Term Follow Up Activities The Iowa Newborn Screening Program (INSP) is administered by the Iowa Department of Health (IDPH) in collaboration with the University of Iowa State Hygienic Laboratory (SHL) to provide testing and the Stead Department of Pediatrics at the University of Iowa Stead Family Children’s Hospital to provide follow up services. Iowa Newborn Screening Dried Blood Spot Program Report Short Term and Long Term Follow Up Activities The following report describes the purpose, processes and activities of the short term and long term follow up program component of the Iowa Newborn Screening Program. There is an appendix listing terms and definitions that readers may wish to refer to while reviewing this document. Program staff members are willing to answer any questions the reader might have. Contact information is provided at the end of the report. Why Do Blood Spot Newborn Screening? Blood spot newborn screening can detect disorders that are life threatening or life changing before an untoward event occurs. Babies can look and act perfectly healthy but still have one of these disorders. Sometimes, it’s literally a matter of a few hours to a few days before tragedy can occur without newborn screening. It is estimated that 12,000 babies are positively impacted by newborn screening efforts in the United States each year. Newborn blood spot screening saves babies lives – it’s as simple as that. An Overview of the Laboratory and Clinical Process of Newborn Screening in Iowa Local Hospital - At 24-48 hours of age, a few drops of blood are taken from a baby’s heel to perform the newborn screening test.
    [Show full text]
  • Biochemistry Entry of Fructose and Galactose
    Paper : 04 Metabolism of carbohydrates Module : 06 Entry of Fructose and Galactose Dr. Vijaya Khader Dr. MC Varadaraj Principal Investigator Dr.S.K.Khare,Professor IIT Delhi. Paper Coordinator Dr. Ramesh Kothari,Professor UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA Dr. S. P. Singh, Professor Content Reviewer UGC-CAS Department of Biosciences Saurashtra University, Rajkot-5, Gujarat-INDIA Dr. Charmy Kothari, Assistant Professor Content Writer Department of Biotechnology Christ College, Affiliated to Saurashtra University, Rajkot-5, Gujarat-INDIA 1 Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose Description of Module Subject Name Biochemistry Paper Name 04 Metabolism of Carbohydrates Module Name/Title 06 Entry of Fructose and Galactose 2 Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose METABOLISM OF FRUCTOSE Objectives 1. To study the major pathway of fructose metabolism 2. To study specialized pathways of fructose metabolism 3. To study metabolism of galactose 4. To study disorders of galactose metabolism 3 Metabolism of Carbohydrates Biochemistry Entry of Fructose and Galactose Introduction Sucrose disaccharide contains glucose and fructose as monomers. Sucrose can be utilized as a major source of energy. Sucrose includes sugar beets, sugar cane, sorghum, maple sugar pineapple, ripe fruits and honey Corn syrup is recognized as high fructose corn syrup which gives the impression that it is very rich in fructose content but the difference between the fructose content in sucrose and high fructose corn syrup is only 5-10%. HFCS is rich in fructose because the sucrose extracted from the corn syrup is treated with the enzyme that converts some glucose in fructose which makes it more sweet.
    [Show full text]