DOCSLIB.ORG

Galactosemia Galactosemia Galactosemia Newborn Screening (NBS) Panels in All 50 States Include Galactosemia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Galactosemia Galactosemia Galactosemia Newborn Screening (NBS) Panels in All 50 States Include Galactosemia Galactosemia Galactosemia Galactosemia Newborn screening (NBS) panels in all 50 states include galactosemia. For patients identified through NBS as at risk for galactose-1-phosphate uridylyltransferase (GALT) deficiency, EGL Genetics recommends measuring the activity of red blood cell (RBC) GALT and the metabolite galactose-1-phosphate (GAL-1-P). If deficient GALT activity (the most common form of galactosemia) and/or elevated Gal-1-P are detected, confirmatory molecular analysis by GALT gene sequencing and testing for the common 5kb deletion can be initiated using DNA extracted from the same sample, upon request. If NBS reveals normal GALT activity but elevated galactose, EGL Genetics offers enzymatic panels to detect deficiencies in galactokinase (GALK) activity. Confirmatory molecular testing is also recommended to identify mutations in patients diagnosed with either enzymatic deficiency. NBS methods vary by state, and may not detect all defects in galactose metabolism. If galactosemia is suspected, particularly a variant form, clinical enzyme analysis and molecular confirmation is available for patients of any age. The combination of biochemical and molecular testing assures an almost 100% detection rate for galactosemia. If a diagnosis of galactosemia is made, clinical monitoring is available through measurement of RBC GAL-1-P and urinary galactitol levels. EGL Genetics can interpret these results in the context of the individual’s known enzyme deficiency. EGL Genetics also offers a targeted CGH array with deletion/duplication analysis of the GALT gene, when mutations are not detected by gene sequencing. Combined enzymatic and full-gene sequencing or if appropriate, targeted sequencing analysis for carrier testing of family members, is also recommended to provide families with reproductive risk information. Test Code Test Name CPT®** Codes GL Galactosemia: Galactitol Quantitative, Urine 82570 (x1), 84378 (x1) GR Galactosemia, Classic: Carrier Testing (GALT Enzyme Activity), Red Blood Cells 82775 (x1) GS Galactosemia: Classic Galactosemia Panel 82775 (x1), 84311 (x1), 84378 (x1) GT Galactosemia: GALT Enzyme Activity 82487 (x1), 82775 (x1), 85018 (x1) GP Galactose-1-Phosphate Profile 84378 (x1) GK Galactosemia (Galactokinase Deficiency): GALK Enzyme Activity 82658 (x1), 82759 (x1), 84311 (x1) SG Galactosemia: GALT Full Gene Sequencing 81406 (x1) DGALT Galactosemia: GALT Gene Deletion/Duplication 81228 (x1) JU Galactosemia (Epimerase): GALE Full Gene Sequencing 81479 (x1) JV Galactosemia (Epimerase): GALE Gene Deletion/Duplication 81228 (x1) IQ Galactosemia (Galactokinase Deficiency): GALK1 Full Gene Sequencing 81479 (x1) JA Galactosemia (Galactokinase Deficiency): GALK1 Gene Deletion/Duplication 81228 (x1) **CPT® is a registered trademark of the American Medical Association. Galactosemia GalactosemiaGalactosemia AboutAbout EGL EGL Genetics Genetics EGLEGL Genetics Genetics specializes specializes in in genetic genetic diagnostic diagnostic testing, testing, with with ne nearlyarly 50 50 years years of of clinical clinical experience experience and and board-certified board-certified labora laboratorytory directorsdirectors and and genetic genetic counselors counselors reporting reporting out out cases. cases. EGL EGL Genet Geneticsics offers offers a acombined combined 1000 1000 molecular molecular genetics, genetics, biochemical biochemical genetics,genetics, and and cytogenetics cytogenetics tests tests under under one one roof roof and and custom custom test testinging for for all all medically medically relevant relevant genes, genes, for for domestic domestic andand international international clients. clients. EquallyEqually important important to to improving improving patient patient care care through through quality quality genetic genetic testing testing is is the the contribution contribution EGL EGL Genetics Genetics makes makes back back to to the the scientificscientific andand medicalmedical communities.communities. EGL EGL Genetics Genetics is is one one of of only only a a fewfew clinical clinical diagnostic diagnostic laboratories laboratories to to openly openly share share data data with with thethe NCBI NCBI freely freely available available public public database database ClinVar ClinVar (>35,000 (>35,000 variants variants on on >1700 >1700 genes) genes) and and is isalso also the the only only laboratory laboratory with with a freea free onlineonline database database (EmVClass), (EmVClass), featuring featuring a avariant variant classification classification search search and and report report request request interface, interface, which which facilitates facilitates rapid rapid interactiveinteractive curation curation andand reportingreporting of of variants. variants. EGLEGL Genetics Genetics Galactosemia Galactosemia Diagnosis Diagnosis Algorithm Algorithm NBS:NBS: ↓ ↓ GALT GALT Enz. Enz. NBS:NBS: nl nGALTl GALT Enz. Enz. (Total(Total Gal Gal Not Not Determined) Determined) (↑( ↑Total Total Gal Gal) ) GalactosemiaGalactosemia Panel Panel Gal-1-PGal-1-P (GALT(GALT Enz., Enz., Gal-1-P) Gal-1-P) If GALTIf GALT enz. enz. is nlis withnl with nl ornl or ↑↑ Gal-1-P Gal-1-P and and galactosemia galactosemia GALTGALT Enz. Enz. <25%, <25%, GALTGALT Enz. Enz. >25%, >25%, is stillis still suspected suspected nln orl or ↑ ↑ Gal-1-P Gal-1-P nln Gal-1-Pl Gal-1-P BiochemicalBiochemical BiochemicalBiochemical ReportReport Issued Issued ReportReport Issued Issued nl nGALTl GALT Enz., Enz., nl nGALTl GALT Enz., Enz., ↑↑ Gal-1-P Gal-1-P nl nGal-1-Pl Gal-1-P If Ifrequested, requested, fullfull gene gene sequencing sequencing willwill be be initiated initiated fromfrom the the same same GALEGALE Enzyme Enzyme GALKGALK Enzyme Enzyme samplesample Analysis*Analysis* Analysis*Analysis* GALTGALT Sequencing Sequencing and and 5kb5kb Deletion Deletion Analysis Analysis BiochemicalBiochemical ReportReport Issued Issued If requested,If requested, ComprehensiveComprehensive fullfull gene gene sequencing sequencing ReportReport Issued Issued willwill be be initiated initiated (Molecular(Molecular and and Biochemical) Biochemical) fromfrom the the same same sample sample GALEGALE or orGALK GALK SequencingSequencing ComprehensiveComprehensive ReportReport Issued Issued (Molecular(Molecular and and Biochemical) Biochemical) *These*These tests tests may may be be ordered ordered as asa panel. a panel. ForFor more more information information about about EGL EGL and and the the nearly nearly 1100 1100 tests tests we weoffer: offer: EMAILEMAIL CALLCALL WEBWEB [email protected]@emory.edu 404-778-8499404-778-8499 www.geneticslab.emory.eduwww.geneticslab.emory.edu.
Load more

Recommended publications
  • 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]
  • 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]
  • 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]
  • Dismetabolic Cataracts
    ndrom Sy es tic & e G n e e n G e f T o Journal of Genetic Syndromes Cavallini et al., J Genet Syndr Gene Ther 2013, 4:7 h l e a r n a r p u DOI: 10.4172/2157-7412.1000165 y o J & Gene Therapy ISSN: 2157-7412 Case Report Open Access Dismetabolic Cataracts: Clinicopathologic Overview and Surgical Management with B-MICS Technique Cavallini GM1, Forlini M1, Masini C1, Campi L1, Chiesi C1, Rejdak R2 and Forlini C3* 1Institute of Ophthalmology, University of Modena, Modena, Italy 2Department of Ophthalmology, Medical University of Lublin, Lublin, Poland 3Department of Ophthalmology, “Santa Maria Delle Croci” Hospital, Ravenna, Italy Abstract Background: Dismetabolic cataract is a loss of lens transparency due to an insult to the nuclear or lenticular fibers, caused by a metabolic disorder. The lens opacification may occur early or later in life, and may be isolated or associated to particular syndromes. We describe some of these metabolic conditions associated with cataract formation, and in particular we report our experience with a patient affected by lathosterolosis that presented bilateral cataracts. Methods: Our patient was a 7-years-old little girl diagnosed with lathosterolosis at age 2 years, through gas cromatography/mass spectrometry method for plasma sterol profile that revealed a peak corresponding to cholest- 7-en-3β-ol (lathosterol). Results: The lens samples obtained during surgical removal with B-MICS technique were sent to the Department of Pathology and routinely processed and stained with haematoxylin-eosin and PAS; then, they were examined under a light microscope. Histological examination revealed lens fragments with the presence of fibers disposed in a honeycomb way, samples characterized by the presence of homogeneous eosinophilic lens fibers, and other fragments characterized by bulgy elements referable to cortical fibers with degenerative characteristics.
    [Show full text]
  • Mild Galactosemia General Overview
    Mild Galactosemia General Overview Q. What is mild galactosemia? A. Mild galactosemia affects the way the body processes the sugar galactose, a component of milk and dairy products. Children with mild galactosemia may have some difficulty processing galactose. As a result, galactose and other by-products can build up in the bloodstream. Q. Is there only one form of galactosemia? A. No, there are several forms. Mild galactosemia is a term used to describe the non-severe forms that usually do not require treatment. Q. How does the body normally process galactose? A. The body normally converts galactose into glucose, which is used for energy. This conversion is made possible by several enzymes. One of these, named galactose-1-phosphate uridyltransferase (GALT), is most often associated with mild galactosemia. Q. What happens to galactose in a child with mild galactosemia? A. In a child with mild galactosemia, the body has some difficulty converting galactose to glucose. This can result in some build-up of galactose and other by-products. Q. What are the effects of having mild galactosemia if it is not treated? A. Most infants who have mild galactosemia have no effects, even without treatment. Depending on the level of enzyme activity and milk intake, some infants may show signs of poor feeding and digestion. Q. What is the treatment for mild galactosemia? A. Mild galactosemia usually does not require treatment. However, some infants may benefit from reduced milk intake. If a child with mild galactosemia has difficulty tolerating breast milk or regular formula, soy based formula can be substituted.
    [Show full text]
  • Metabolic Liver Diseases Presenting As Acute Liver Failure in Children
    R E V I E W A R T I C L E Metabolic Liver Diseases Presenting as Acute Liver Failure in Children SEEMA A LAM AND BIKRANT BIHARI LAL From Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India. Correspondence to: Prof Seema Alam, Professor and Head, Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110 070, India. [email protected] Context: Suspecting metabolic liver disease in an infant or young child with acute liver failure, and a protocol-based workup for diagnosis is the need of the hour. Evidence acquisition: Data over the last 15 years was searched through Pubmed using the keywords “Metabolic liver disease” and “Acute liver failure” with emphasis on Indian perspective. Those published in English language where full text was retrievable were included for this review. Results: Metabolic liver diseases account for 13-43% cases of acute liver failure in infants and young children. Etiology remains indeterminate in very few cases of liver failure in studies where metabolic liver diseases were recognized in large proportion. Galactosemia, tyrosinemia and mitochondrial disorders in young children and Wilson’s disease in older children are commonly implicated. A high index of suspicion for metabolic liver diseases should be kept when there is strong family history of consanguinity, recurrent abortions or sibling deaths; and history of recurrent diarrhea, vomiting, failure to thrive or developmental delay. Simple dietary modifications and/or specific management can be life-saving if instituted promptly. Conclusion: A high index of suspicion in presence of red flag symptoms and signs, and a protocol-based approach helps in timely diagnosis and prompt administration of life- saving therapy.
    [Show full text]
  • Galactosaemia in an Infant: Case Report F.V
    May 1999 EAST AFRICAN MEDICAL JOURNAL 28 1 East Atiican Medical Journal Vol. 76 No 5 May 1999 GALACTOSAEMIA IN AN INFANT: CASE REPORT F.V. Murila. MBChB. MMed, Lecturer, Department of Paediatrics and Child Health College of Health Sciences, University of Nairobi, P.O. Box 19676, Nairobi GALACTOSAEMIA IN AN INFANT: CASE REPORT F.V. MURILA SUMMARY Galactosaemia is a disorder of galactose metabolism in which raised levels of galactose and galactose-1-phosphate damage various organs. It is a very rare disease (incidence 1 in 60,000) and the diagnosis is often missed, leading to poor prognosis. A case of clinical galactosaemia that was diagnosed at the age of 11 months is reported. It is important to be aware of this condition as early treatment may prevent some of the complications. INTRODUCTION Assay of the respective enzyme in the red blood cell, white blood cell and fibroblasts shows a deficiency Galactosaemia is a very rare disorder of galactose of the enzyme(4). Red blood cells (RBC) lactose-l- metabolism whose mode of inheritance is autosomal phosphate levels are high(2). recessive(1). It is characterised by a deficiency of any Treatment consists of dietary restriction of lactose. of three enzymes. These are galactokinase, galactose- Inspite of strict lactose restriction, however, neurological I-phosphate uridyl transferase (GALT) and uridyl and gonadal damage are relentlessly progressive(2,5). diphosphogalactose-4-epimerase. A deficiency of galactokinase leads to an increase in serum galactose CASE REPORT - with subsequent galactosuria The excess galactose is converted to galactitol which leads to cataract formation. J.M.was well until the age of three months when he Intelligence is spared.
    [Show full text]
  • An Unexpectedly High Frequency of Hypergalactosemia in an Immigrant Bosnian Population Revealed by Newborn Screening
    0031-3998/02/5105-0598 PEDIATRIC RESEARCH Vol. 51, No. 5, 2002 Copyright © 2002 International Pediatric Research Foundation, Inc. Printed in U.S.A. An Unexpectedly High Frequency of Hypergalactosemia in an Immigrant Bosnian Population Revealed by Newborn Screening SUSANNE REICH, JULIA HENNERMANN, BARBARA VETTER, LUITGARD M. NEUMANN, YOON S. SHIN, ARIANE SÖLING, EBERHARD MÖNCH, AND ANDREAS E. KULOZIK Children’s Hospital [S.R., J.H., B.V., E.M., A.E.K], Department of Human Genetics [L.M.N.], Charité, Campus Virchow, Humboldt University, D-10247 Berlin, Germany; Children’s Hospital, Ludwig-Maximilian-University, D-80337 Munich, Germany [Y.S.S.]; Department of Neurosurgery, Martin-Luther-University, D-06097 Halle, Germany [A.S.] ABSTRACT In galactokinase (GALK) deficiency, galactose cannot be in Berlin since 1991. In two of these families, GALK deficiency phosphorylated into galactose-1- phosphate, which leads to cat- was subsequently diagnosed in siblings who had cataract surgery aract formation. Neonatal screening for hypergalactosemia in at4and5yofage, respectively. In all these 10 Bosnian patients, Berlin has been performed by thin-layer chromatography since a homozygous P28T mutation located near the active center of 1978, which detects classical galactosemia and GALK defi- the enzyme was identified. We propose that neonatal screening of ciency. Until 1991, GALK deficiency has not been identified in populations with a significant proportion of Bosnians and possi- a total of Ϸ260,000 samples. In contrast, from 1992 to 1999, nine bly other southeastern Europeans, e.g. Romani, should be par- patients were detected in a total of Ϸ240,000 screened newborns. ticularly directed toward GALK deficiency, an inborn error of One Turkish patient was homozygous for two novel S142I/ metabolism that is readily amenable to effective treatment.
    [Show full text]
  • Antenatal Diagnosis of Inborn Errors Ofmetabolism
    816 ArchivesofDiseaseinChildhood 1991;66: 816-822 CURRENT PRACTICE Arch Dis Child: first published as 10.1136/adc.66.7_Spec_No.816 on 1 July 1991. Downloaded from Antenatal diagnosis of inborn errors of metabolism M A Cleary, J E Wraith The introduction of experimental treatment for Sample requirement and techniques used in lysosomal storage disorders and the increasing prenatal diagnosis understanding of the molecular defects behind By far the majority of antenatal diagnoses are many inborn errors have overshadowed the fact performed on samples obtained by either that for many affected families the best that can amniocentesis or chorion villus biopsy. For be offered is a rapid, accurate prenatal diag- some disorders, however, the defect is not nostic service. Many conditions remain at best detectable in this material and more invasive only partially treatable and as a consequence the methods have been applied to obtain a diagnos- majority of parents seek antenatal diagnosis in tic sample. subsequent pregnancies, particularly for those disorders resulting in a poor prognosis in terms of either life expectancy or normal neurological FETAL LIVER BIOPSY development. Fetal liver biopsy has been performed to The majority of inborn errors result from a diagnose ornithine carbamoyl transferase defi- specific enzyme deficiency, but in some the ciency and primary hyperoxaluria type 1. primary defect is in a transport system or Glucose-6-phosphatase deficiency (glycogen enzyme cofactor. In some conditions the storage disease type I) could also be detected by biochemical defect is limited to specific tissues this method. The technique, however, is inva- only and this serves to restrict the material avail- sive and can be performed by only a few highly able for antenatal diagnosis for these disorders.
    [Show full text]
  • Galactosemia, Or Galactose Diabetes
    EDITORIALS over the years can recall certain patients with whom usually described as glycogen but might be galactogen. each of these measures seemed to be successful. How- In the eyes the lenses often show lamellar or nuclear ever, with none of them is relief obtained with any sig- cataracts. nificant degree of uniformity; and in a situation in The cause of these pathologic cellular changes is de- which various agents appear curative, it is doubtful if batable. Mason and Turner5 blamed the lowering of any is specific. The last word in the management of dia- blood glucose. But the absence of similar cellular damage betic neuropathy remains to be said and the present in disorders such as glycogen storage disease and hyper- state of the problem presents a real challenge to all in- insulinism, associated with low blood sugar, makes this 6 7 terested in diabetes. hypothesis doubtful. Several authors have suggested - ALEXANDER MARBLE, M.D. that the elevated blood galactose was a direct cause of Joslin Clinic, Boston the pathologic cellular abnormalities. Some investigat- ors8- 9 have produced lens opacities in rats by feeding large amounts of galactose. Dam's experiments10 with the GALACTOSEMIA, OR GALACTOSE feeding of galactose to chicks led him to the conclusion DIABETES that galactose damaged the central nervous system. Craig 11 Galactosemia, sometimes called galactose diabetes, is and Maddock have described the production of lens caused by an inborn error of metabolism that leads to opacities by high galactose diet in rats, associated with inability of the body tissues to utilize galactose. The failure of growth, increased urinary nitrogen and amino- aciduria, but without hepatocellular changes.
    [Show full text]
  • Review Galactokinase: Structure, Function and Role in Type II
    CMLS, Cell. Mol. Life Sci. 61 (2004) 2471–2484 1420-682X/04/202471-14 DOI 10.1007/s00018-004-4160-6 CMLS Cellular and Molecular Life Sciences © Birkhäuser Verlag, Basel, 2004 Review Galactokinase: structure, function and role in type II galactosemia H. M. Holden a,*, J. B. Thoden a, D. J. Timson b and R. J. Reece c,* a Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706 (USA), Fax: +1 608 262 1319, e-mail: [email protected] b School of Biology and Biochemistry, Queen’s University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, (United Kingdom) c School of Biological Sciences, The University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, (United Kingdom), Fax: +44 161 275 5317, e-mail: [email protected] Received 13 April 2004; accepted 7 June 2004 Abstract. The conversion of beta-D-galactose to glucose unnatural sugar 1-phosphates. Additionally, galactoki- 1-phosphate is accomplished by the action of four en- nase-like molecules have been shown to act as sensors for zymes that constitute the Leloir pathway. Galactokinase the intracellular concentration of galactose and, under catalyzes the second step in this pathway, namely the con- suitable conditions, to function as transcriptional regula- version of alpha-D-galactose to galactose 1-phosphate. tors. This review focuses on the recent X-ray crystallo- The enzyme has attracted significant research attention graphic analyses of galactokinase and places the molecu- because of its important metabolic role, the fact that de- lar architecture of this protein in context with the exten- fects in the human enzyme can result in the diseased state sive biochemical data that have accumulated over the last referred to as galactosemia, and most recently for its uti- 40 years regarding this fascinating small molecule ki- lization via ‘directed evolution’ to create new natural and nase.
    [Show full text]