Please enable JavaScript.
Coggle requires JavaScript to display documents.
INBORN ERRORS OF METABOLISM (IEM) (What is a Metabolic Disease? (Small…
INBORN ERRORS OF METABOLISM (IEM)
Inborn Errors of Metabolism
An inherited enzyme deficiency leading to the disruption of normal bodily metabolism
Eg: Inborn errors of metabolism are rare genetic disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food.
What is a Metabolic Disease?
Inborn Error : an inherited (i.e. genetic) disorder
Metabolism : chemical or physical changes undergone by substances in a biological system
Any disease originating in our chemical individuality
Majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrates) into others (products).
IEMs :In Review
Traditionally the inherited metabolic diseases were categorized as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism, or lysosomal storage diseases.
In recent decades, hundreds of new inherited disorders of metabolism have been discovered and the categories have proliferated.
What is a Metabolic Disease?
Small Molecule Disease
Carbohydrate
Protein
Lipid
Nucleic Acids
Organelle Disease
Lysosomes
Mitochondria
Peroxisomes
Cytoplasm
Inborn Errors of Metabolism
Accumulation of a toxic substrate (compound acted upon by an enzyme in a chemical reaction)
Impaired formation of a product normally produced by the deficient enzyme.
Three Types of IEM
Type 3: Neurological Deterioration
Examples:
Tay Sachs disease is a genetic disorder caused by a missing enzyme that results in the accumulation of a fatty substance in the nervous system. This results in disability and death.
Gaucher disease is a rare genetic disorder that results in accumulation of fatty molecules called cerebrosides
DNA analysis show: mutations
Type 2: Acute Metabolic Crises
Life threatening in infancy
Children are protected in utero by maternal circulation which provide missing product or remove toxic substance
Example:Urea Cycle Disorders (Eg: OTC, AG)
deficiency of one of the enzymes in the urea cycle which is responsible for removing ammonia from the blood stream
Type 1: Silent Disorders
Do not manifest life-threatening crises
Untreated could lead to brain damage and developmental disabilities
When treatment is begun early and well-maintained, affected children can expect normal development and a normal life span.
Example: PKU (Phenylketonuria)
People with this disease have difficulty breaking down and using the amino acid phenylalanine.
Treatment
Dietary Restriction
Supplement deficient product
Stimulate alternate pathway
Supply vitamin co-factor
Organ transplantation
Enzyme replacement therapy
Gene Therapy
Major Categories of Inherited Metabolic Diseases
Disorders of carbohydrate metabolism
E.g. glycogen storage disease
Disorders of amino acid metabolism
E.g. phenylketonuria, maple syrup urine disease, glutaric acidemia type 1
Disorders of organic acid metabolism (organic acidurias)
E.g.alcaptonuria
Disorders of fatty acid oxidation and mitochondrial metabolism
E.g. medium chain acyl dehydrogenase deficiency (glutaric acidemia type 2)
Glycogen Storage Disease
(Synonyms: glycogenosis, dextrinosis) is any one of several inborn errors of metabolism that result from enzyme defects that affect the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types.