Part 3: Inborn Errors of Metabolism

“The art of medicine cannot be inherited, nor can it be copied from books….”
– Paracelsus –
Inborn Errors of Metabolism

The other major branch of congenital disorders are the inborn errors of metabolism (IEMs). These interesting disorders involve structural defects on a molecular scale and we understand them through the study of biochemistry. Often they will not announce themselves until well after birth, or even well into adult life. Many are inherited in an autosomal recessive fashion.

An example is Wilson’s Disease, an inborn error of copper metabolism. The specific defect is an inherited deficiency of ceruloplasmin, the copper carrying protein. Inability to excrete copper normally (through the bile) leads to the damaging accumulation of copper in the body tissues, especially in the liver, eye and brain, where the basal ganglia are especially vulnerable.

When considering errors of metabolism, it is helpful to consider the different biochemical materials of which the human body is composed. These are broadly divided in the sieve, so that the clinician can systematically think through each, further enabling the logical elucidation of the causes of disease.
Samuel Alexander Kinnier Wilson (1878-1937). Wilson was born in the USA, but when his father died when Samuel was just one his family moved to Edinburgh. He was a gifted student. As a doctor he specialised in neurology, studying with a famed group at Queen’s Square, London. He was a quick-witted man and a superb teacher, said to be extremely stimulating for students.
Wilson studied his cases clinically and then followed them to autopsy in the classic method of clinicopathological correlation. His dedication to truth was unquestionable. After two diagnostically challenging patients had been released from hospital, he kept close survey of their whereabouts, awaiting their death. To his great concern one of them went to Switzerland when the end was near. He assiduously followed the patient’s moves, and when death arrived, gathered his money and flew to Zurich to conduct the autopsy himself. Satisfyingly, his theories on the patient were confirmed.
Wilson had five pieces of advice to students:
1. Never show surprise.
2. Never say the same thing twice to a patient.
3. Be decisive in your indecision.
4. Never take a meal with your patient.
5. Never believe what the patient said the doctor said.