An Overview of Biochemical Genetics

J. Daniel Sharer1

1 University of Alabama at Birmingham, Birmingham, Alabama
Publication Name:  Current Protocols in Human Genetics
Unit Number:  Unit 17.1
DOI:  10.1002/0471142905.hg1701s89
Online Posting Date:  April, 2016
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


Biochemical genetics focuses on the pathophysiology, diagnosis, and treatment of inherited metabolic disorders. While individually rare, the combined incidence of these diseases makes them a significant source of morbidity and mortality, particularly among infants and young children, and new conditions continue to be identified. Inherited metabolic disorders may present as an acute, life‐threatening illness or with more chronic, progressive symptoms. Population‐scale newborn screening allows for early detection and treatment for >40 different metabolic disorders. This introductory unit is intended to provide an overview of the different clinical categories of metabolic disorders, including a description of modern diagnostic methods and treatment options. © 2016 by John Wiley & Sons, Inc.

Keywords: biochemical genetics; metabolism; enzyme; mass spectrometry; enzyme‐replacement therapy; newborn screening

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • The Diagnostic Laboratory
  • Mitochondrial Disorders
  • Congenital Disorders of Glycosylation
  • Other Disorders
  • Biochemical Methods
  • Newborn Screening
  • Treatment of Metabolic Disorders
  • Figures
  • Tables
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

  Barth, M.L., Ward, C., Harris, A., Saad, A., and Fensom, A. 1994. Frequency of arylsulphatase A pseudodeficiency associated mutations in a healthy population. J. Med. Genet. 31:667‐671. doi: 10.1136/jmg.31.9.667.
  Beadle, G.W. and Tatum, E.L. 1941. Genetic control of biochemical reactions in neurospora. PNAS 27:499‐506. doi: 10.1073/pnas.27.11.499.
  Desnick, R.J. 2004. Enzyme replacement and enhancement therapies for lysosomal diseases. J. Inherit. Metab. Dis. 27:385‐410. doi: 10.1023/B:BOLI.0000031101.12838.c6.
  Desnick, R.J. and Schuchman, E.H. 2012. Enzyme replacement therapy for lysosomal diseases: Lessons from 20 years of experience and remaining challenges. Annu. Rev. Genomics Hum. Genet. 13:307‐335. doi: 10.1146/annurev-genom-090711-163739.
  Freeze, H.H. 2014. Solving glycosylation disorders: Fundamental approaches reveal complicated pathways. Am. J. Hum. Gen. 94:161‐175 doi: 10.1016/j.ajhg.2013.10.024.
  Garrod, A.E. 1902. The incidence of alkaptonuria: A study in chemical individuality. Lancet II:1616‐1620. doi: 10.1016/S0140-6736(01)41972-6.
  Guthrie, R. 1988. Maternal PKU: A continuing problem. Am. J. Public Health 78:771. doi: 10.2105/AJPH.78.7.771.
  Guthrie, R. and Susi, A. 1963. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 32:338‐343.
  Levy, H.L., Vargas, J.E., Waisbren, S.E., Kurczynski, T.W., Roeder, E.R., Schwartz, R.S., Rosengren, S., Prasad, C., Greenberg, C.R., Gilfix, B.M., MacGregor, D., Shih, V.E., Bao, L., and Kraus, J.P. 2002. Reproductive fitness in maternal homocystinuria due to cystathionine beta‐synthase deficiency. J. Inherit. Metab. Dis. 25:299‐314. doi: 10.1023/A:1016502408305.
  Marsden, D. and Levy, H. 2010. Newborn screening of lysosomal storage disorders. Clin. Chem. 56:1071‐1079. doi: 10.1373/clinchem.2009.141622.
  Matern, D., Tortorelli, S., Oglesbee, D., Gavrilov, D., and Rinaldo, P. 2007. Reduction of the false‐positive rate in newborn screening by implementation of MS/MS‐based second‐tier tests: The Mayo Clinic experience (2004–2007). J. Inherit. Metab. Dis. 30:585‐592. doi: 10.1007/s10545-007-0691-y.
  Millington, D.S., Kodo, N., Norwood, D.L., and Roe, C.R. 1990. Tandem mass spectrometry: A new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism. J. Inherit. Metab. Dis. 13:321‐324. doi: 10.1007/BF01799385.
  Morbidity and Mortality Weekly Report (MMWR). 2011. Centers for Disease Control and Prevention. 60:814‐818.
  Nagan, N., Kruckeberg, K.E., Tauscher, A.L., Bailey, K.S., Rinaldo, P., and Matern, D. 2003. The frequency of short‐chain acyl‐CoA dehydrogenase gene variants in the U.S. population and correlation with the C(4)‐acylcarnitine concentration in newborn blood spots. Mol. Genet. Metab. 78:239‐346. doi: 10.1016/S1096-7192(03)00034-9.
  Pauling, L., Itano, H.A., Singer, S.J., and Wells, I.C. 1949. Sickle Cell Anemia, a molecular disease. Science 110:543‐548. doi: 10.1126/science.110.2865.543.
  Raghuveer, T.S., Garg, U., and Graf, W.D. 2006. Inborn errors in metabolism in infancy and early childhood: An update. Am. Fam. Physician 73:1981‐1990.
  Triggs‐Raine, B.L., Mules, E.H., Kaback, M.M., Lim‐Steele, J.S., Dowling, C.E., Akerman, B.R., Natowicz, M.R., Grebner, E.E., Navon, R., and Welch, J.P. 1992. A pseudodeficiency allele common in non‐Jewish Tay‐Sachs carriers: Implications for carrier screening. Am. J. Hum. Genet. 51:793‐801.
  The Metabolic and Molecular Bases of Inherited Disease (online version). Charles R. Scriver, Arthur L. Beaudet, David Valle, William S. Sly, Bert Vogelstein, Barton Childs, and Kenneth W. Kinzler, eds. Published by McGraw‐Hill.
  Online Mendelian Inheritance in Man (OMIM). McKusick‐Nathans Institute for Genetic Medicine, Johns Hopkins University and National Center for Biotechnology Information, National Library of Medicine. OMIM (UNIT ) is a non‐sequence‐based catalog of human genes and genetic disorders that provides concise textual information from the literature on most human conditions having a genetic basis, as well as pictures illustrating the condition or disorder.
  GeneReviews. 1993‐2015. Roberta A. Pagon, Margaret P. Adam, Holly H. Ardinger, Stephanie E. Wallace, Anne Amemiya, Lora J.H. Bean, Thomas D. Bird, Chin‐To Fong, Heather C. Mefford, Richard J.H. Smith, and Karen Stephens, eds. University of Washington, Seattle.
PDF or HTML at Wiley Online Library