ALAD

The ALAD gene provides instructions for making an enzyme known as delta-aminolevulinate dehydratase. This enzyme is involved in the production of a molecule called heme. Heme is vital for all of the body's organs, although it is found mostly in the blood, bone marrow, and liver. Heme is an essential component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).

The production of heme is a multi-step process that requires eight different enzymes. Delta-aminolevulinate dehydratase is responsible for the second step in this process, which combines two molecules of delta-aminolevulinic acid (the product of the first step) to form a compound called porphobilinogen. In subsequent steps, four molecules of porphobilinogen are combined and then modified to produce heme.

porphyria - caused by mutations in the ALAD gene

At least 10 mutations in the ALAD gene can cause a rare form of porphyria called ALAD deficiency porphyria. Most of these mutations change single protein building blocks (amino acids) in delta-aminolevulinate dehydratase. These changes reduce the activity of the enzyme, allowing delta-aminolevulinic acid to build up to toxic levels in the body. This compound is formed during the normal process of heme production, but reduced activity of delta-aminolevulinate dehydratase allows it to accumulate to toxic levels. Very high levels of this compound can cause attacks of abdominal pain, vomiting, and other signs and symptoms of ALAD deficiency porphyria.

other disorders - associated with the ALAD gene

A common variation (polymorphism) in the ALAD gene may affect the risk of developing lead poisoning in people exposed to environmental lead. Lead is a heavy metal that is toxic when inhaled or ingested. Lead poisoning can cause significant health problems involving the nervous system, blood, kidneys, and reproductive system.

The ALAD variation that has been studied most extensively replaces the amino acid glycine with the amino acid cysteine at position 177 in delta-aminolevulinate dehydratase (written as Gly177Cys or G177C). This variation may influence the amount of lead in a person's blood and bones. Although some studies suggest that this variation increases the risk of lead poisoning, other studies have not found such an association.