Disorders of Branched-Chain Amino Acid Metabolism

This very rare disease (1: 200,000) is caused by a defect in the enzyme alpha-decarboxylase, so that the three amino acids leucine, isoleucine and valine cannot be converted.

As a result, these accumulate in the blood and urine and – similar to PKU – primarily damage the brain. The consequences are seizures, drinking and muscle weakness or stiffness, developmental disorders and even coma.

Typically, the patients and especially their urine have an odor similar to Maggi or maple syrup. If left untreated, the disease leads to death after a few months; permanent damage can only be prevented by starting a special diet (enriched with special amino acids) at an early stage, which must be followed for the rest of the patient’s life. However, there are also milder courses in which the enzyme defect and symptoms are only mild.

Organoacidopathies (organoacidemias, organacidurias).

A variety of inherited metabolic disorders are grouped under this umbrella term. Almost always, as in the diseases already described, there is a specific enzyme defect, as a result of which amino or fatty acids cannot be properly broken down, accumulate in the organism, and thus cause damage. Especially in situations that put a strain on the body (such as fever, infections, operations, vaccinations), life-threatening crises can occur due to hyperacidity (acidosis).

It is believed that one in 2,500 children in Germany is affected, although the severity and prognosis vary greatly. Depending on the enzyme affected, three courses are distinguished:

  1. Sudden, massive symptoms in newborns only a few days after feeding (for example, drinking and muscle weakness, vomiting, loss of consciousness up to coma).
  2. First appearance of symptoms only in infancy (failure to thrive and development, vomiting, seizures).
  3. Characteristic combination of neurological symptoms such as gait disturbances, muscle tension and convulsions.

Therapeutically, a specific diet is usually necessary, in which the triggering foods are omitted. In addition, many disorders require additional substances to be taken. It is also important that acute, life-threatening metabolic derailments are avoided and that the affected parents and children are trained for emergencies.

Disorders of metabolism of sulfur-containing amino acids.

  • Cystinosis: In this rare genetic defect (frequency 1 : 50,000 to 100,000), cystine cannot be transported out of the body’s cells and is therefore deposited there. In the kidneys, this leads to damage to the cells and to a functional disorder that ultimately requires blood washing. In addition, growth retardation and bone softening also occur. The deposits in the cornea of the eye cause lacrimation and photophobia. Later, thyroid disorders, enlargement of the liver and diabetes also occur. Therapeutically, adequate water intake is important, in addition to salts, vitamin D and medications are given.
  • Homocystinuria: In this very rare disorder (frequency 1 : 250,000) is usually a defect of cystathionine synthetase, an enzyme that converts homocysteine – derived from methionine – into cystathionine. Homocysteine is therefore converted instead into homocystine, which primarily damages the blood vessels and can lead to life-threatening blood clots. Other symptoms include tall stature, slippage of the eye lens, and spider fineness. Treatment consists of a lifelong diet and additional administration of vitamin B6 or cystine.