Arts syndrome

Overview

Arts Syndrome is a very rare X-linked recessive genetic disorder characterized by a combination of neurological, immunological, and developmental impairments. It primarily affects males and is marked by hypotonia (low muscle tone), sensorineural hearing loss, recurrent infections, developmental delay, and progressive neurological decline. The syndrome was first described in a Dutch family and named after the family in which it was originally identified.

Because of its genetic basis and severe progression, Arts syndrome often leads to early mortality in affected males, while carrier females may show milder symptoms or remain asymptomatic.

Causes

Arts Syndrome is caused by mutations in the PRPS1 gene (phosphoribosyl pyrophosphate synthetase 1), located on the X chromosome. This gene encodes an enzyme involved in purine metabolism, which is essential for nucleotide synthesis and energy regulation in cells.

The PRPS1 mutations seen in Arts Syndrome result in a loss of enzymatic function, which disrupts the metabolic processes in cells, especially in the nervous system and immune system. Because the condition is X-linked recessive, it typically affects males more severely, while females may be carriers with partial or no symptoms.

Symptoms

Symptoms of Arts Syndrome often appear in infancy or early childhood and worsen with time. Key features include:

Neurological Symptoms:

• Congenital or early-onset hypotonia (floppiness)

• Delayed motor milestones

• Ataxia (poor coordination and balance)

• Progressive loss of motor function

• Intellectual disability or global developmental delay

Hearing and Vision:

• Severe sensorineural hearing loss

• Optic atrophy in some cases (leading to vision impairment)

Immune System and General Health:

• Recurrent, severe infections (especially respiratory infections)

• Failure to thrive

• Fatigue or poor feeding

Diagnosis

Diagnosis of Arts Syndrome is based on clinical features, family history, and confirmatory genetic and enzymatic testing. Diagnostic steps include:

• Clinical evaluation: Identification of characteristic neurological, hearing, and immunological symptoms

• Hearing tests: Audiometry to confirm sensorineural hearing loss

• Genetic testing: Detection of pathogenic mutations in the PRPS1 gene

• Enzyme assay: Measurement of PRPS1 enzyme activity in cultured fibroblasts or blood cells

• Family history: Evaluation for other affected male relatives or carrier status in females

Treatment

There is no cure for Arts Syndrome, and treatment is supportive and focused on managing individual symptoms and preventing complications:

Neurological and Developmental Support:

• Physical and occupational therapy for motor function

• Speech and language therapy for communication

• Assistive devices and mobility aids as needed

Hearing and Vision Management:

• Hearing aids or cochlear implants for deafness

• Regular ophthalmological evaluations if optic atrophy is present

Infection Prevention and Immune Support:

• Prophylactic antibiotics and immunoglobulin therapy for recurrent infections

• Vaccinations and close monitoring during illness

Experimental and Supportive Therapies:

• Research is ongoing into potential therapies targeting purine metabolism

• Multidisciplinary care is essential for symptom management and quality of life

Prognosis

The prognosis for individuals with Arts Syndrome is generally poor, especially in males with complete loss-of-function mutations. Most affected males succumb to infections or progressive neurological decline in early childhood. However, with aggressive supportive care, life expectancy may be extended in some cases.

Carrier females typically have a normal lifespan but may show mild neurological or hearing symptoms depending on X-chromosome inactivation patterns. Genetic counseling is strongly recommended for affected families.