PRPS1
phosphoribosyl pyrophosphate synthetase 1
Normal Function
Health Conditions Related to Genetic Changes
Arts syndrome
At least three PRPS1 gene mutations have been identified in people with Arts syndrome, a disorder that causes serious neurological problems in males. Females can also be affected by this condition, but they typically have much milder symptoms.
The PRPS1 gene mutations that cause Arts syndrome change single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme. The mutations are believed to result in the production of an unstable enzyme with little or no activity. The lack of functional PRPP synthetase 1 enzyme disrupts both the manufacture and recycling of purines. The manufacture of pyrimidines is also affected, but not the pyrimidine salvage pathway. The disruption of purine production, and to a lesser extent pyrimidine production, may impair energy storage and transport in cells. Impairment of these processes may have a particularly severe effect on tissues that require a large amount of energy, such as the nervous system, resulting in the neurological problems characteristic of Arts syndrome.
More About This Health ConditionRelated Conditions
Arts syndromePhosphoribosylpyrophosphate synthetase superactivityCharcot-Marie-Tooth diseaseNonsyndromic hearing loss
Health Conditions Related to Genetic Changes
At least three PRPS1 gene mutations have been identified in people with Arts syndrome, a disorder that causes serious neurological problems in males. Females can also be affected by this condition, but they typically have much milder symptoms.
The PRPS1 gene mutations that cause Arts syndrome change single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme. The mutations are believed to result in the production of an unstable enzyme with little or no activity. The lack of functional PRPP synthetase 1 enzyme disrupts both the manufacture and recycling of purines. The manufacture of pyrimidines is also affected, but not the pyrimidine salvage pathway. The disruption of purine production, and to a lesser extent pyrimidine production, may impair energy storage and transport in cells. Impairment of these processes may have a particularly severe effect on tissues that require a large amount of energy, such as the nervous system, resulting in the neurological problems characteristic of Arts syndrome.
At least seven mutations in the PRPS1 gene that cause a severe form of phosphoribosylpyrophosphate synthetase superactivity (PRS superactivity) have been identified. These mutations change single amino acids in the PRPP synthetase 1 enzyme, resulting in a poorly regulated, overactive enzyme. In a milder form of PRS superactivity, the PRPS1 gene is overactive for reasons that are not well understood. PRPS1 gene overactivity increases the production of normal PRPP synthetase 1 enzyme, which increases the availability of PRPP. In both forms of the disorder, excessive amounts of purines are generated.
Under these conditions, uric acid, a waste product of purine breakdown, accumulates in the body. A buildup of uric acid can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints. Affected individuals may also develop kidney or bladder stones formed from uric acid crystals.
People with the severe form of PRS superactivity have additional symptoms including loss of hearing caused by changes in the inner ear (sensorineural hearing loss), weak muscle tone (hypotonia), impaired muscle coordination (ataxia), and developmental delay. It is unclear how the PRPS1 gene mutations that cause the severe form of PRS superactivity are related to these neurological problems.
MedlinePlus Genetics provides information about Charcot-Marie-Tooth disease
MedlinePlus Genetics provides information about Nonsyndromic hearing loss