What is a metabolic disease?

Garrods hypothesis

A B C product
deficiency
substrate excess D
toxic metabolite
INBORN ERRORS OF METABOLISM
 Inborn Errors of Metabolism
An inherited enzyme deficiency leading to
the disruption of normal bodily
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
 Categories of IEMs are as follows:
Disorders of protein metabolism (eg, amino
acidopathies, organic
acidopathies, and urea cycle defects)
Disorders of carbohydrate metabolism (eg,
carbohydrate intolerance disorders,
glycogen storage disorders, disorders of
gluconeogenesis and glycogenolysis)
Lysosomal storage disorders
Fatty acid oxidation defects
Mitochondrial disorders
Phenylketonuria
 PKU
No acute clinical symptoms
Untreated leads to mental retardation
Associated complications: behavior
disorders, cataracts, skin disorders, and
movement disorders
First newborn screening test was
developed in 1959
Treatment: phenylalaine restricted diet
(specialized formulas available)
Albinism
 ORGANIC ACIDURIA
Disorder Enzyme

Methyl malonic Methyl malony COA mutase.

Acidemia.

Propionic Acidemia. Propionyl COA Carboxylase.

Multiple carboxylase Malfunction of all

deficiency. carboxylase.

Ketothiolase deficiency . 2 methylacetyl COA thiolase

def.
Methionine synthesis
Homocystinuria
Homocystinuria
WHAT IS HEREDITARY TYROSINEMIA?
-genetic inborn error of metabolism
-associated with severe liver disease in
infancy
-autosomal recessive disorder (two copies of
defective gene)
- Incidence - one person in 100 000 globally
Maple syrup urine
disease