Reviewed July 2009
What is the official name of the ALAD gene?
The official name of this gene is “aminolevulinate dehydratase.”
ALAD is the gene's official symbol. The ALAD gene is also known by other names, listed below.
What is the normal function of the ALAD gene?
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.
How are changes in the ALAD gene related to health conditions?
- 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.
Where is the ALAD gene located?
Cytogenetic Location: 9q33.1
Molecular Location on chromosome 9: base pairs 116,148,591 to 116,163,617
The ALAD gene is located on the long (q) arm of chromosome 9 at position 33.1.
More precisely, the ALAD gene is located from base pair 116,148,591 to base pair 116,163,617 on chromosome 9.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about ALAD?
You and your healthcare professional may find the following resources about ALAD helpful.
Educational resources - Information pages
- Biochemistry (fifth edition, 2002): Mammalian Porphyrins Are Synthesized from Glycine and Succinyl Coenzyme A (http://www.ncbi.nlm.nih.gov/books/NBK22446/)
- KidsHealth from the Nemours Foundation: Lead Poisoning (http://kidshealth.org/parent/medical/brain/lead_poisoning.html)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for ALAD (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=210%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(ALAD%20AND%20gene%5BTIAB%5D)%20AND%20((5-aminolevulinate%20hydro-lyase%5BTIAB%5D)%20OR%20(ala-dehydrase%5BTIAB%5D)%20OR%20(aminolevulinic%20acid%20dehydratase%5BTIAB%5D)%20OR%20(delta-aminolevulinate%20dehydratase%5BTIAB%5D)%20OR%20(porphobilinogen%20synthase%5BTIAB%5D)%20OR%20(delta-aminolevulinic%20acid%20dehydratase%5BTIAB%5D)%20OR%20(aminolevulinate%20hydro-lyase%5BTIAB%5D)%20OR%20(ALA%20dehydratase%20porphyria))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/125270)
Research Resources - Tools for researchers
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=210)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=395)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/210)
What other names do people use for the ALAD gene or gene products?
- 5-aminolevulinate dehydratase
- 5-Aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing)
- aminolevulinate, delta-, dehydratase
- Aminolevulinate Hydro-Lyase
- Aminolevulinic Acid Dehydratase
- delta-Aminolevulinate Dehydratase
- delta-Aminolevulinic Acid Dehydratase
- Porphobilinogen Synthase
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding ALAD?
amino acid ;
bone marrow ;
nervous system ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Akagi R, Kato N, Inoue R, Anderson KE, Jaffe EK, Sassa S. delta-Aminolevulinate dehydratase (ALAD) porphyria: the first case in North America with two novel ALAD mutations. Mol Genet Metab. 2006 Apr;87(4):329-36. Epub 2005 Dec 15. (http://www.ncbi.nlm.nih.gov/pubmed/16343966?dopt=Abstract)
- Akagi R, Nishitani C, Harigae H, Horie Y, Garbaczewski L, Hassoun A, Mercelis R, Verstraeten L, Sassa S. Molecular analysis of delta-aminolevulinate dehydratase deficiency in a patient with an unusual late-onset porphyria. Blood. 2000 Nov 15;96(10):3618-23. (http://www.ncbi.nlm.nih.gov/pubmed/11071662?dopt=Abstract)
- Badminton MN, Elder GH. Molecular mechanisms of dominant expression in porphyria. J Inherit Metab Dis. 2005;28(3):277-86. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15868463?dopt=Abstract)
- Jaffe EK, Stith L. ALAD porphyria is a conformational disease. Am J Hum Genet. 2007 Feb;80(2):329-37. Epub 2006 Dec 21. (http://www.ncbi.nlm.nih.gov/pubmed/17236137?dopt=Abstract)
- Jaffe EK. The porphobilinogen synthase catalyzed reaction mechanism. Bioorg Chem. 2004 Oct;32(5):316-25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15381398?dopt=Abstract)
- Kauppinen R. Porphyrias. Lancet. 2005 Jan 15-21;365(9455):241-52. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15652607?dopt=Abstract)
- Kelada SN, Shelton E, Kaufmann RB, Khoury MJ. Delta-aminolevulinic acid dehydratase genotype and lead toxicity: a HuGE review. Am J Epidemiol. 2001 Jul 1;154(1):1-13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11427399?dopt=Abstract)
- Maruno M, Furuyama K, Akagi R, Horie Y, Meguro K, Garbaczewski L, Chiorazzi N, Doss MO, Hassoun A, Mercelis R, Verstraeten L, Harper P, Floderus Y, Thunell S, Sassa S. Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria. Blood. 2001 May 15;97(10):2972-8. (http://www.ncbi.nlm.nih.gov/pubmed/11342419?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/210)
- Sassa S, Akagi R, Nishitani C, Harigae H, Furuyama K. Late-onset porphyrias: what are they? Cell Mol Biol (Noisy-le-grand). 2002 Feb;48(1):97-101. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11929054?dopt=Abstract)
- Scinicariello F, Murray HE, Moffett DB, Abadin HG, Sexton MJ, Fowler BA. Lead and delta-aminolevulinic acid dehydratase polymorphism: where does it lead? A meta-analysis. Environ Health Perspect. 2007 Jan;115(1):35-41. (http://www.ncbi.nlm.nih.gov/pubmed/17366816?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.