PURA disease is a rare genetic neurological disorder that impacts neurodevelopment. First identified in medical literature in 2014, this condition affects the nervous system, leading to a range of developmental and physical challenges. Awareness of PURA disease is growing as more individuals are diagnosed through advanced genetic testing.
Understanding PURA Disease
PURA disease is a neurodevelopmental disorder caused by a genetic alteration in the PURA gene on chromosome 5. This alteration can involve a “spelling mistake,” a small insertion or deletion, or a larger missing segment. The condition is typically de novo, meaning it occurs spontaneously and is not inherited from parents.
The PURA gene provides instructions for creating a protein called Pur-alpha (Purα), which plays several roles within cells, including regulating gene activity and assisting in DNA replication. This protein is particularly important for healthy brain development, guiding the growth and division of nerve cells (neurons). Purα may also contribute to the formation and maturation of myelin, the protective substance that insulates nerves and facilitates efficient signal transmission.
Disruption of the PURA gene reduces functional Purα protein, impairing neuronal processes. This explains the profound neurological effects in individuals with PURA disease. It is understood to alter normal brain development and neuron function.
Recognizing the Signs
Individuals with PURA disease often present with a wide array of clinical manifestations, affecting various body systems. These signs typically appear at birth or during early infancy. Developmental delays are a consistent feature, encompassing motor skills, such as sitting and walking, and speech. Most affected individuals experience moderate to severe intellectual disability, with expressive language skills generally more impacted than their ability to understand spoken language.
Neurological symptoms include weak muscle tone (hypotonia), often seen in newborns. Feeding difficulties, including swallowing problems, can persist. Many individuals also experience excessive sleepiness and low body temperature. Breathing irregularities, such as pauses or slow breathing, are also reported.
Epilepsy and seizures are also frequently observed, with onset often before the age of five. Seizure types can vary, including uncontrolled muscle jerks (myoclonus) and generalized tonic-clonic seizures. These seizures can be challenging to manage, with some individuals experiencing drug-resistant epilepsy. Other less common but associated features include abnormalities of the heart, eyes, urogenital tract, gastrointestinal tract, and skeleton, such as scoliosis or hip dysplasia.
Diagnosis and Confirmation
Diagnosing PURA disease relies primarily on genetic testing, as its clinical features can overlap with other neurological conditions. Genetic testing identifies mutations or deletions within the PURA gene, which is the definitive diagnostic method. This testing is typically performed using a blood sample, which is then analyzed for specific genetic alterations.
Common genetic testing methods include whole exome sequencing or whole genome sequencing. A more focused gene panel test may also be used. Clinical evaluation and suggestive symptoms guide healthcare providers in pursuing genetic testing. Parental testing is often conducted to confirm if the PURA gene alteration is new and to assess recurrence risk.
Managing the Condition
Management of PURA disease focuses on addressing individual symptoms, as there is currently no cure. Treatment involves a multidisciplinary approach to improve quality of life. This team may include:
A pediatrician
A neurologist
A geneticist
A pulmonologist
An ophthalmologist
An occupational therapist
A physical therapist
A speech-language pathologist
Physical therapy helps improve mobility, balance, and range of motion, while occupational therapy assists with daily tasks and fine motor skills. Speech therapy is provided to support communication development, and for individuals with severe expressive language difficulties, augmentative and alternative communication (AAC) aids may be explored. Feeding therapy is also frequently employed to address swallowing difficulties and ensure adequate nutrition, sometimes involving specialized feeding devices.
Medications are often prescribed to manage specific symptoms, such as seizures or sleep disturbances. While some individuals respond well to anti-epileptic drugs, drug-resistant seizures are common, requiring ongoing evaluation and adjustment of treatment plans. For sleep issues, certain medications like gabapentin may enhance sleep quality, while others, such as benzodiazepines, can negatively affect it. Regular medical follow-ups are important to monitor development, assess for new symptoms, and adjust therapies as needed, including surveillance for musculoskeletal complications like scoliosis. Family support and resources also play a significant role in navigating the challenges associated with PURA disease.