Primary Hyperoxaluria: Type 1

Primary hyperoxaluria type 1 (PH1) is an inherited disorder that is caused by the deficiency of a liver enzyme named alanine:glyoxylate-aminotransferase (AGT). People with PH1 have excessive accumulation of insoluble calcium salts in various tissues of the body, especially the kidney. PH1 causes recurrent kidney stones, which, if untreated, can cause life-threatening kidney failure. Other complications include short stature, vision loss, heart block, and bone and nerve pain. Onset of symptoms begins before 4-6 months for about one fifth of affected individuals. For the majority of affected individuals, symptoms begin in late childhood or early adolescence; the remaining affected individuals do not have symptoms until adulthood. Intellect is not affected by PH1. PH1 may be treated by high doses of vitamin B6 in some affected people. Organ transplantation of the liver and kidneys may treat or perhaps cure this disease. PH1 is caused by pathogenic variants in the AGXT gene.

Primary hyperoxaluria type 1 is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for PH1. However, the risk to have a child affected with PH1 is increased. Testing of reproductive partners is recommended for carriers of PH1.

It is estimated that PH1 occurs in 1 in 120,000 newborns in Europe; whereas worldwide it is estimated to affect between one to three in one million people. PH1 frequency is higher in Tunisia and Iran due to the high rate of consanguinity.

Genetics Home Reference: Primary hyperoxaluria (http://ghr.nlm.nih.gov/)
Genetic Alliance: Primary hyperoxaluria type I (http://www.diseaseinfosearch.org/)
Oxalosis and Hyperoxaluria Foundation (http://www.ohf.org/)

OMIM [Hyperoxaluria, Primary, Type I: 259900] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Primary hyperoxaluria type 1 (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing