Inherited Metabolic Diseases 1902 – Genetic Disorders

Inherited metabolic diseases, in which particular chemical pathways in the body are disrupted, such as alkaptonuria (also known as "inherited inborn errors of metabolism, IEM"), were investigated by British physician Archibald Edward Garrod in 1902. 

Today, we know that these genetic diseases are generally transmitted through recessive genes, meaning that a person may develop the disease if they inherit a defective gene from both their father and their mother. In most cases, these defective genes cause deficient or faulty production of an enzyme that controls the rate of chemical reactions. Abnormal enzymes can cause harmful chemicals to accumulate in the body.

Hundreds of inherited diseases are known today, a few of which are listed here. 

• Alkaptonuria results from a defective enzyme involved in breaking down the amino acid tyrosine. A toxic byproduct of tyrosine accumulates and can damage cartilage and heart valves. 
• Phenylketonuria (PKU) results from a deficiency of a liver enzyme needed to metabolize the amino acid phenylalanine. If diagnosed early, PKU can be controlled by restricting foods rich in phenylalanine (such as meat and milk). If untreated, PKU can cause severe intellectual disability. 
• Thalassemia is a group of metabolic disorders affecting hemoglobin synthesis.
• Tay-Sachs disease is associated with deficiency of an enzyme needed to metabolize a particular class of fats and is more common among Jews of Eastern European origin. Mental abilities deteriorate, and the patient dies before reaching the teenage years. 

Possible treatments for IEM, including bone marrow transplantation and gene transfer, continue to be investigated.

Description of the Article Image: Many inborn errors of metabolism are inherited in an "autosomal recessive" pattern, as shown. At the top, both the father and the mother carry one copy of the gene that can cause the disease (orange). The child who inherits the orange gene from both parents (on the right) develops the disease.

Historical Figures Mentioned in This Article: Archibald Edward Garrod (1857–1936)

• Previous topic: The Chromosomal Theory of Inheritance 1902 – The Birth of Cytogenetics
• Next topic: The Cause of Sleeping Sickness 1902 – The Tsetse Fly