Biomarkers in Inborn Errors of Metabolism : Clinical Aspects and Laboratory Determination

__Biomarkers of Inborn Errors in Metabolism: Clinical Aspects and Laboratory Determination__ is structured around the new reality that laboratory testing and biomarkers are an integral part in the diagnosis and treatment of inherited metabolic diseases. The book covers currently used biomarkers as well as markers that are in development. Because biomarkers used in the initial diagnosis of disease may be different than the follow-up markers, the book also covers biomarkers used in both the prognosis and treatment of inherited metabolic disorders. With the introduction of expanded new-born screening for inborn metabolic diseases, an increasing numbers of laboratories are involved in follow-up confirmatory testing. The book provides guidance on laboratory test selection and interpreting results in patients with suspected inherited metabolic diseases. The book provides comprehensive guidance on patient diagnosis and follow-up through its illustrative material on metabolic pathways, genetics and pathogenesis, treatment and prognosis of inherited metabolic diseases, along with essential information on clinical presentation. Each chapter is organized with a uniform, easy-to-follow format: a brief description of the disorder and pathway; a description of treatment; biomarkers for diagnosis; biomarkers followed for treatment efficacy; biomarkers followed for disease progression; confounding conditions that can either: affect biomarker expression or mimic IEMs; other biomarkers: less established, future.

Biomarkers of Inborn Errors in Metabolism: Clinical Aspects and Laboratory Determination is structured around the new reality that laboratory testing and biomarkers are an integral part in the diagnosis and treatment of inherited metabolic diseases. The book covers currently used biomarkers as well as markers that are in development. Because biomarkers used in the initial diagnosis of disease may be different than the follow-up markers, the book also covers biomarkers used in both the prognosis and treatment of inherited metabolic disorders.

With the introduction of expanded new-born screening for inborn metabolic diseases, an increasing numbers of laboratories are involved in follow-up confirmatory testing. The book provides guidance on laboratory test selection and interpreting results in patients with suspected inherited metabolic diseases. The book provides comprehensive guidance on patient diagnosis and follow-up through its illustrative material on metabolic pathways, genetics and pathogenesis, treatment and prognosis of inherited metabolic diseases, along with essential information on clinical presentation.

Each chapter is organized with a uniform, easy-to-follow format: a brief description of the disorder and pathway; a description of treatment; biomarkers for diagnosis; biomarkers followed for treatment efficacy; biomarkers followed for disease progression; confounding conditions that can either: affect biomarker expression or mimic IEMs; other biomarkers: less established, future.

• Provides comprehensive information on the tests/biomarkers selection in newborn screening and follow-up of newborn screens
• Categorizes biomarkers into diagnostic markers, disease follow-up markers, and prognostic biomarkers
• Covers confounding factors that can alter biomarkers in the absence of inborn errors of metabolism
• Offers guidance on how to distinguish acquired causes from inborn errors of metabolism

8.8.2 Leber Hereditary Optic Neuropathy (OMIM #535000) -- 8.8.3 Leigh Syndrome (OMIM #256000) and Neuropathy, Ataxia, Retinitis Pigmentosa Syndrome (OMIM #551500) -- 8.8.4 Maternally Inherited Diabetes-Deafness Syndrome (OMIM #520000) -- 8.8.5 Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-Like Episodes (OMIM #540000) -- 8.8.6 Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (OMIM #603041) -- 8.8.7 Myoclonic Epilepsy with Ragged Red Fibers Syndrome (OMIM #545000) -- 8.8.8 Pearson Marrow-Pancreas Syndrome (OMIM #557000) -- 8.8.9 Progressive External Opthalmoplegia and Kearns-Sayre Syndrome (OMIM #530000) -- 8.9 Conclusion -- References -- 9 Lysosomal storage disorders: mucopolysaccharidoses -- 9.1 Introduction -- 9.2 Brief Description of Clincial Presentations -- 9.3 Mucopolysaccharidoses -- 9.3.1 MPS I (Hurler, Hurler-Scheie, and Scheie Syndromes) -- 9.3.2 MPS II (Hunter Syndrome) -- 9.3.3 MPS III A, B, C, and D (Sanfilippo Syndrome, Type A, B, C, and D) -- 9.3.4 MPS IV (Morquio Syndrome) -- 9.3.5 MPS VI (Maroteaux-Lamy Syndrome) -- 9.3.6 MPS VII (Sly Syndrome) -- 9.3.7 MPS IX -- 9.4 Other Diseases With MPS-Like Phenotypes -- 9.4.1 Multiple Sulfatase Deficiency -- 9.4.2 Sialidosis or Mucolipidoses I (ML I) -- 9.4.3 Mucolipidosis II (ML II or I-Cell Disease) and Mucolipidosis III (ML III or Pseudo-Hurler Polydystrophy) -- 9.4.4 Mucolipidosis IV (ML IV) -- 9.5 Glycosaminoglycans and GAGS Analysis -- 9.5.1 Total GAGs Analysis by Dimethylene Blue Binding Assay -- 9.5.2 Qualitative Fractionation of GAGs -- 9.5.3 LC-MS/MS Analyses -- 9.6 Laboratory Diagnosis of MPS Disorders -- 9.7 Brief Description of Treatment -- 9.8 Conclusion -- Acknowledgment -- References -- 10 Lysosomal storage disorders: sphingolipidoses -- 10.1 Introduction -- 10.2 Overview of Sphingolipids Metabolism -- 10.3 Sphingolipidoses -- 10.3.1 GM1 Gangliosidosis 4.2.1 Carnitine Transporter Defect -- 4.2.2 Carnitine Palmitoyltransferase 1 Deficiency -- 4.2.3 Carnitine/Acylcarnitine Translocase Defect -- 4.2.4 Carnitine Palmitoyltransferase 2 Deficiency -- 4.3 Disorders of Fatty Acid Oxidation -- 4.4 Very Long-Chain Acyl-CoA Dehydrogenase Deficiency -- 4.5 Medium-Chain Acyl-CoA Dehydrogenase Deficiency -- 4.6 Short-Chain Acyl-CoA Dehydrogenase Deficiency -- 4.7 Long-Chain L-3-Hydroxyacyl-CoA Dehydrogenase and Mitochondrial Trifunctional Protein Deficiencies -- 4.8 Medium/Short-Chain L-3-Hydroxy-Acyl-CoA Dehydrogenase -- 4.9 Multiple Acyl-CoA Dehydrogenase Deficiency -- References -- 5 Urea cycle and other disorders of hyperammonemia -- 5.1 Introduction -- 5.2 Brief Description of Clinical Presentation -- 5.3 Urea Cycle Disorders -- 5.3.1 N-acetylglutamate Synthase (NAGS) Deficiency -- 5.3.2 Carbamoylphosphate Synthetase (CPS1) Deficiency -- 5.3.3 Ornithine Transcarbamylase (OTC) Deficiency -- 5.3.4 Argininosuccinate Synthetase Deficiency -- 5.3.5 Argininosuccinate Lyase Deficiency -- 5.3.6 Arginase Deficiency -- 5.3.7 Mitochondrial Ornithine Transporter (SLC25A15) Defect -- 5.3.8 Mitochondrial Aspartate-Glutamate Carrier (Citrin SLC25A13) Defect/Citrullinemia Type 2 -- 5.4 Other Inborn Defects Associated With Hyperammonemia -- 5.4.1 Lysinuric Protein Intolerance -- 5.4.2 Disorders of Ornithine Metabolism -- 5.4.3 Pyruvate Carboxylase Deficiency, French Form -- 5.4.4 Hyperinsulinism-Hyperammonemia -- 5.4.5 Organic Acidurias -- 5.4.6 Fatty Acid Oxidation Defects -- 5.4.7 Other -- 5.5 Confounding Conditions That Can Cause Hyperammonemia -- 5.5.1 Liver Disease -- 5.5.2 Transient Hyperammonemia of the Newborn (THAN) -- 5.5.3 Drug Therapy -- 5.5.4 Other Conditions -- 5.6 Biomarkers for Differential Diagnosis of Hyperammonemia -- 5.6.1 Plasma Ammonia -- 5.6.2 Plasma and Urine Amino Acid Profiles 2.7.2 Brief Description of Treatment -- 2.7.3 Biomarkers for Diagnosis -- 2.7.4 Biomarkers Followed for Treatment Efficacy -- 2.7.5 Other Biomarkers: Less Established, Future -- 2.8 Hypermethioninemia -- 2.8.1 Brief Description of the Disorder and Pathway -- 2.8.2 Brief Description of Treatment -- 2.8.3 Biomarkers for Diagnosis -- 2.8.4 Biomarkers Followed for Treatment Efficacy -- 2.8.5 Biomarkers Followed for Disease Progression -- 2.8.6 Confounding Conditions That Can Cause Hypermethioninemia -- 2.8.7 Other Biomarkers: Less Established, Future -- 2.9 Hyperprolinemia -- 2.9.1 Brief Description of the Disorder and Pathway -- 2.9.2 Brief Description of Treatment -- 2.9.3 Biomarkers for Diagnosis -- 2.10 Sulfocysteinuria -- 2.10.1 Brief Description of the Disorder and Pathway -- 2.10.2 Brief Description of Treatment -- 2.10.3 Biomarkers for Diagnosis -- 2.10.4 Biomarkers Followed for Treatment Efficacy -- 2.10.5 Confounding Conditions -- 2.11 Cystinuria (OMIM: 220100) -- 2.11.1 Brief Description of the Disorder and Pathway -- 2.11.2 Brief Description of Treatment -- 2.11.3 Biomarkers for Diagnosis -- 2.11.4 Biomarkers Followed for Treatment Efficacy -- 2.11.5 Biomarkers Followed for Disease Progression -- 2.11.6 Other Biomarkers: Less Established, Future -- Acknowledgment -- References -- 3 Organic acid disorders -- 3.1 Introduction -- 3.2 Selected Organic Acid Disorders -- 3.2.1 Propionic acidemia (PA) -- 3.2.2 Methylmalonic acidemia -- 3.2.3 Isovaleric acidemia -- 3.2.4 Multiple carboxylase deficiency (holoenzyme synthetase and biotinidase) -- 3.2.5 Glutaric acidemia, type 1 -- 3.2.6 3-Methylcrotonyl-CoA carboxylase deficiency -- 3.3 Other Organic Acid Disorders -- 3.3.1 Spurious organic acids -- References -- 4 Disorders of mitochondrial fatty acid [beta]-oxidation -- 4.1 Introduction -- 4.2 Disorders of Carnitine Transport Front Cover -- Biomarkers in Inborn Errors of Metabolism -- Copyright Page -- Contents -- List of Contributors -- Biographies -- Preface -- 1 Introduction to laboratory diagnosis and biomarkers in inborn error of metabolism -- 1.1 Introduction -- 1.2 Laboratory Biomarkers and Tests in Diagnosis of IEM -- 1.3 Specimen Types -- 1.4 Specimen Collection and Processing -- 1.5 Specimen Analysis, Quality Control, and Quality Assurance -- 1.6 Method Selection and Evaluation -- 1.7 Treatment and Prognosis -- References -- 2 Amino acids disorders -- 2.1 Introduction -- 2.2 Phenylketonuria (PKU) -- 2.2.1 Brief Description of the Disorder and Pathway -- 2.2.2 Brief Description of Treatment -- 2.2.3 Biomarkers for Diagnosis -- 2.2.4 Biomarkers Followed for Treatment Efficacy -- 2.3 Non-PKU Hyperphenylalaninemias -- 2.3.1 Brief Description of the Disorder and Pathway -- 2.3.2 Brief Description of Treatment -- 2.3.3 Biomarkers for Diagnosis -- 2.3.4 Biomarkers Followed for Treatment Efficacy -- 2.4 Tyrosinemias -- 2.4.1 Brief Description of the Disorder and Pathway -- 2.4.2 Biomarkers for Diagnosis -- 2.4.3 Biomarkers Followed for Treatment Efficacy -- 2.4.4 Confounding Conditions -- 2.5 Nonketotic Hyperglycinemia (Glycine Encephalopathy) -- 2.5.1 Brief Description of the Disorder and Pathway -- 2.5.2 Brief Description of Treatment -- 2.5.3 Biomarkers for Diagnosis -- 2.5.4 Biomarkers Followed for Treatment Efficacy -- 2.5.5 Other Biomarkers -- 2.6 Maple Syrup Urine Disease -- 2.6.1 Brief Description of the Disorder and Pathway -- 2.6.2 Brief Description of Treatment -- 2.6.3 Biomarkers for Diagnosis -- 2.6.4 Biomarkers Followed for Treatment Efficacy -- 2.6.5 Biomarkers Followed for Disease Progression -- 2.6.6 Other Biomarkers: Less Established, Future -- 2.7 Homocystinuria -- 2.7.1 Brief Description of the Disorder and Pathway 5.6.3 Urine Organic Acid and Acylcarnitine Profiles -- 5.7 Biomarkers Followed for Treatment Efficacy and Disease Progression -- 5.7.1 Ammonia -- 5.7.2 Plasma Amino Acid Profile -- 5.7.3 Carnitine -- 5.7.4 Other Biomarkers -- 5.8 Brief Description of Treatment -- 5.9 Conclusions -- Acknowledgment -- References -- 6 Newborn screening -- 6.1 Newborn Screening -- 6.2 Amino Acid Disorders -- 6.3 Organic Acidemias -- 6.4 Fatty Acid Oxidation Disorders -- 6.5 Region 4 Stork -- 6.6 Galactosemia -- 6.7 Biotinidase Deficiency -- 6.8 Conclusion -- References -- 7 Carbohydrate disorders -- 7.1 Introduction -- 7.2 Galactosemia -- 7.2.1 Clinical Presentation -- 7.2.2 Treatment -- 7.2.3 Biomarkers for Differential Diagnosis -- 7.2.4 Biomarkers Followed for Treatment Efficacy -- 7.2.5 Confounding Conditions -- 7.3 Inborn Errors in Fructose Metabolism -- 7.3.1 Clinical Presentation -- 7.3.2 Confounding Conditions -- 7.3.3 Biomarkers for Differential Diagnosis -- 7.3.4 Treatment -- 7.3.5 Biomarkers Followed for Treatment Efficacy -- 7.4 Glycogen Storage Diseases -- 7.4.1 Clinical Presentation -- 7.4.2 Confounding Conditions -- 7.4.3 Biomarkers for Differential Diagnosis -- 7.4.4 Treatment -- 7.4.5 Biomarkers Followed for Treatment Efficacy -- 7.5 Conclusions -- References -- 8 Mitochondrial disorders -- 8.1 Introduction -- 8.2 Clinical Presentation -- 8.3 Genetics -- 8.4 Diagnosis -- 8.5 Diagnostic Studies -- 8.5.1 Biochemical Testing -- 8.5.1.1 Metabolic panel and creatine kinase -- 8.5.1.2 Lactate and pyruvate levels -- 8.5.1.3 Plasma amino acid profile -- 8.5.1.4 Urine organic acid profile -- 8.5.1.5 Carnitine -- 8.5.1.6 Magnetic resonance spectroscopy -- 8.5.1.7 Whole exome sequencing -- 8.6 Treatment -- 8.7 Confounding Conditions -- 8.8 Selected Disorders -- 8.8.1 Alpers-Huttenlocher Syndrome (OMIM #203700) Content: Front-matter,Copyright,Dedication,List of Contributors,Biographies,PrefaceEntitled to full textChapter 1 - Introduction to laboratory diagnosis and biomarkers in inborn error of metabolism, Pages 1-24 Chapter 2 - Amino acids disorders, Pages 25-64 Chapter 3 - Organic acid disorders, Pages 65-85 Chapter 4 - Disorders of mitochondrial fatty acid β-oxidation, Pages 87-101 Chapter 5 - Urea cycle and other disorders of hyperammonemia, Pages 103-123 Chapter 6 - Newborn screening, Pages 125-153 Chapter 7 - Carbohydrate disorders, Pages 155-166 Chapter 8 - Mitochondrial disorders, Pages 167-190 Chapter 9 - Lysosomal storage disorders: Mucopolysaccharidoses, Pages 191-209 Chapter 10 - Lysosomal storage disorders: Sphingolipidoses, Pages 211-233 Chapter 11 - Peroxisomal disorders: Clinical and biochemical laboratory aspects, Pages 235-282 Chapter 12 - Disorders of purine and pyrimidine metabolism, Pages 283-299 Chapter 13 - Biomarkers for the study of catecholamine and serotonin genetic diseases, Pages 301-329 Chapter 14 - Cerebral creatine deficiency syndromes, Pages 331-341 Chapter 15 - Congenital disorders of glycosylation, Pages 343-360 Chapter 16 - Disorders of vitamins and cofactors, Pages 361-397 Chapter 17 - Disorders of trace metals, Pages 399-426 Index, Pages 427-449 10.3.2 GM2 Gangliosidoses (Tay-Sachs Disease, Sandhoff Disease, and GM2 Activator Protein Deficiency)