1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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
Chapter 19 slides in Children with Disabilities, Seventh Edition, Online Companion Materials. Copyright © 2013 Paul H. Brookes Publishing Co., Inc. All rights reserved.

11. 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.

12. 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.