Arts syndrome is a rare genetic X-linked disease that is characterized by a violation of the synthesis of purine compounds. Pathology occurs when there is a mutation in the PRPS1 gene. The main clinical manifestations include delayed psychomotor development, sensorineural hearing loss, multiple coordination disorders. Diagnosis of the syndrome involves genetic research, ENMG, MRI of brain tissues, tests for nitrogen metabolism products. Supportive treatment: comprehensive rehabilitation programs, installation of cochlear implants, prevention and correction of infectious complications.
E79.8 Other disorders of purine and pyrimidine metabolism
Arts syndrome is part of a group of diseases caused by PRPS1 mutations. Charcot-Marie-Toute disease, X-linked nonsyndromic sensorineural deafness also belong to this category. Art’s syndrome is extremely rare, not always amenable to diagnosis. The prevalence of pathology is less than 1 case per 1 million population. Mutations responsible for the development of clinical symptoms are X-linked, so boys are mostly ill, and girls become carriers or suffer from a mild variant of the disease.
Thanks to modern advances in the field of genetics, it has been established that Arts syndrome is caused by mutations of the PRPS1 gene, which is localized on the long arm of the X chromosome at the Xq22.1-q24.47 locus. The disease is inherited from a healthy mother-carrier of the mutant gene to her sons, who develop a complete clinical picture, and daughters, who are more often they act as carriers. The probability of transmitting the PRPS1 mutation to a child is 50%.
The enzyme phosphoribosyl pyrophosphate synthetase (PPS) is necessary for the first stage of nucleotide formation: the conversion of ribose-5-phosphate to 5-phosphoribosyl-1-pyrophosphate in the phosphorylation reaction. In patients with Arts syndrome, the structure of PPS1 is disrupted, which is mainly located in the nervous tissue, but the function of PPS2 in the liver is preserved, so purines are partially synthesized, and the disease is not fatal.
Nucleotides act as a building material for DNA, participate in the transmission of signals inside the cell, and are components of cellular energy systems. Therefore, the violation of their formation is manifested by serious problems of the functioning of the body, primarily the nervous system. Presumably, severe neurological signs of the syndrome are caused by a decrease in the level of guanosine triphosphate (GTP).
The main signs of pathology include progressive hearing impairment, mental retardation, various disorders of motor activity. The syndrome manifests itself in various combinations of disorders in the first months after the birth of a child. Most of the symptoms appear within 1-2 years of life, and after this age, visual impairment associated with optic nerve atrophy is added.
In patients, a mild or moderate degree of mental retardation is determined, but it is not possible to accurately identify the degree of cognitive impairment due to combined visual and hearing impairments. Disorders of the motor sphere are represented by a decrease in muscle strength and tone, loss of sensitivity in the extremities, changes in reflex activity.
Occasionally, the syndrome is observed in women who are heterozygous carriers of the PRPS1 mutation. Signs occur at the age of over 20 years and consist of progressive hearing loss due to sensorineural hearing loss. Isolated manifestations of other pathognomonic symptoms in female patients are described: ataxia (2 cases), decreased muscle tone (1 case), hyperreflexia (1 case).
Arts syndrome, as a rule, is more severe than other variants of PRPS1 disorders, since it is accompanied by severe immunodeficiency. Patients suffer from recurrent infections of the respiratory tract, digestive tract, opportunistic infections and generalized inflammatory processes. Septic complications often result in the death of a child at an early age.
Visual and auditory analyzer malfunctions, intellectual development delay, motor function disorders — all this leads to early disability. Arts syndrome is characterized by the irreversible nature of pathological disorders, which reduces the life expectancy of patients, worsens its quality, provokes problems with socialization.
A pediatrician who identifies a typical symptom complex for a hereditary disease sends the child for a detailed examination to a genetic center. After detecting clinical signs of Arts syndrome in the patient (mental retardation, hearing loss, motor disorders), a set of diagnostic methods is prescribed:
- Electroneuromyography. With ENMG, a delay in the conduction of nerve impulses is diagnosed, which correlates with severe disorders of peripheral innervation. To clarify the pathological changes, a nerve biopsy is performed, revealing foci of demyelination.
- MRI of the brain. The images show damage to the optic nerves, areas of thinning of the white matter, which indicates demyelinating processes. In some patients with Arts syndrome, MRI results show no signs of organic damage to the central nervous system.
- Molecular genetic testing. Verification of a specific mutation is the only 100% accurate method of confirming the diagnosis. Often, the study is carried out only on the PRPS1 gene, but for differential diagnosis, a multigenic panel is shown by genome sequencing.
- Urine tests. The study determines the absence or low level of hypoxanthine, while the amount of other purines is within the normal range. The uric acid content in the blood is at the lower limit of the norm, which makes it possible to exclude the PPS overactivity syndrome.
The syndrome belongs to the category of incurable diseases, so medical care is aimed at slowing the progression of symptoms, the maximum possible adaptation to life. Patients need lifelong supportive treatment, including in the format of living in specialized rehabilitation centers. Assistance to patients who have Arts syndrome includes several areas, the main of which are:
- Hearing correction. If necessary, cochlear implantation is performed to restore auditory function, improve communication and cognitive skills.
- Improvement of motor activity. To reduce the manifestations of ataxia, patients are shown massage, special exercise therapy complexes, taking medications: B vitamins, angioprotectors, and means to improve metabolism.
- Social rehabilitation. To develop the intellectual skills of the patient, an individual program of classes with oligophrenopedagogues, speech therapists, speech pathologists is assigned.
- Prevention of complications. Due to the high frequency of infections, immunocorrection is recommended, and routine and optional vaccination is also mandatory for children. Antibiotics are used to treat infectious processes.
In medicine, the search for new therapies to control the symptoms of Art’s disease continues. Encouraging results were obtained with the use of S-adenosyl methionine (SAM), which contributed to the reduction of clinical manifestations in 2 patients. The effect of the drug is realized by replenishing purine nucleotides in the body. The therapy is considered experimental and requires further clinical testing.
Prognosis and prevention
Arts syndrome is more severe than other variants of PRPS1 mutations, so it often ends with the death of young boys. For women carriers of the gene, the prognosis is relatively favorable, they have a good quality and life expectancy. The basis of prevention is genetic counseling of families where there have been cases of pathologies suspected of Arts syndrome, which is carried out at the stage of pregnancy planning.