Chapter 19 Inborn Errors of Metabolism Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Inborn Error of Metabolism Enzyme deficiency Can lead to Organ damage/dysfunction Disability Death 1 in 2,500 children born with it Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Types of Inborn Errors of Metabolism Inborn errors of metabolism are often divided into Those that are clinically “silent” for a relatively long period before being recognized Those that produce acute metabolic crises Those that cause progressive organ damage or dysfunction Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Types of Inborn Errors of Metabolism (continued) Silent disorders Abnormalities involving amino acids or hormones Example: phenylketonuria (PKU) Disorders presenting in acute metabolic crises Errors in metabolism of small molecules Example: urea cycle disorders Disorders with progressive neurological deterioration Include glycogen storage and peroxisomal and lysosomal storage disorders Example: Tay-Sachs disease Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Clinical Manifestations Range across types from lack of overt symptoms to life-threatening episodes Silent disorders: children develop slowly, not usually diagnosed with intellectual disability until later in childhood Life-threatening episodes: children develop symptoms such as Vomiting Respiratory distress Lethargy At risk for slipping into coma Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Clinical Manifestations (continued) Progressive disorders, neurological deterioration: present as large molecule, progressive disorder Examples: lysosomal storage disorders, peroxisomal disorders Gradual, progressive loss of motor and/or cognitive skills If untreated, death in childhood Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Mechanism of Brain Damage Causes not completely understood Research providing some clues that may lead to treatment Example: thyroid hormone found to be necessary to normal growth of neurons, so early treatment of congenital thyroid disorder protects brain development Neurotoxins involved in some metabolic disorders Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Associated Disabilities Range of developmental disabilities Most common: intellectual disability and cerebral palsy Some specific impairments Example: boys with the X-linked Lesch-Nyhan syndrome exhibit movement disorder and compulsive, self-injurious behavior Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Diagnostic Testing Children with significant developmental disabilities of unknown origin should be referred for genetic evaluation Increasing number of biochemical and molecular tests available Can lead to specific diagnosis Early identification and treatment can improve outcomes Blood and urine tests used to detect toxins and/or biochemical markers Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Newborn Screening Inborn errors of metabolism are rare Fewer than 1 in 10,000 births Diagnosis is easily missed Screening efforts focused on newborn infants First screening test for PKU in 1959; successful in detecting more than 90% of affected infants More than 30 inborn errors of metabolism can be screened for; varies across states https://www.youtube.com/watch?v=G_qjpjO3gFE https://www.youtube.com/watch?v=yNzhxX0xM5E Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Therapeutic Approaches Substrate deprivation (limiting intake of potentially toxic compound) Supplementing the deficient product Stimulating an alternate metabolic pathway Vitamin co-factor: residual enzyme activity Supplying the enzyme itself Transplanting body organ containing deficient enzyme Gene therapy Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.
Outcome Range of outcomes varies enormously In disorders that can be detected by newborn screening, such as PKU, children who are affected have generally done well Less favorable outcomes occur in other inborn errors of amino acid and organic acid metabolism Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.