PURA Syndrome - An Overview

Introduction

There are more than 6000 known genetic disorders, and among them is a rare condition called PURA syndrome. PURA syndrome is seen in early childhood, affecting the development of muscles, the heart, and the brain. The “PURA” syndrome is named after the affected gene’s name, the “purine-rich element binding protein A”. Though rare, it is important to learn about this syndrome to provide exceptional care and support to the affected individuals.

What Is PURA Syndrome?

PURA syndrome is a neurodevelopmental disorder mainly caused by a genetic mutation (a mistake in the coding of cells). This gene is important for the development of brain cells and communication. Therefore, when this gene does not work properly, it will lead to significant developmental delays, weak muscles, and learning issues.

What Are the Other Names for PURA Syndrome?

The PURA syndrome is also known as PURA-related neurodevelopmental disorder and PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome.

Is PURA Syndrome a Genetic Disease?

PURA syndrome is a genetic disease. It results from a mutation in the PURA gene's deoxyribonucleic acid (DNA) structure, which is necessary for brain development. This gene is present on chromosome 5. In rare cases, the faulty gene is inherited from parents who carry the mutated gene without showing symptoms.

Who Is at Risk for PURA Syndrome?

This condition is rare and can affect both genders. No inheritance pattern is seen, and the mutation occurs randomly; no risk factors are explicitly known. It can happen in any family, regardless of past medical history.

What Are the Symptoms?

The symptoms of PURA syndrome can vary from person to person. Some may have mild delays, whereas others may have more serious issues and physical complications.

Symptoms in Newborn:

1. Low Muscle Tone: This gives the baby the appearance of a floppy baby. Joints will be flexible, especially in fingers, wrists, and elbows. Involuntary movements like jerks can be seen. The child is seen with open lips at rest.

2. Developmental Delays: The children with PURA syndrome have issues with milestones, having significant delays in crawling, sitting, or walking.

3. Sensitive skin.

4. Feeding Issues: The child may have difficulties sucking milk. As the child's swallowing pattern is not developed, there is a risk of aspiration. They are also seen with high-arched palates.

5. A weak, crying baby.

6. Seizures and Epilepsy: These may start in the newborn stage and continue lifelong and may be difficult to control.

7. Breathing Difficulties: Apnea (paused breathing) and hyperventilation (slow breathing) are commonly seen in newborns with this syndrome.

8. Unable to regulate body temperature.

9. Visual Issues: Almond-shaped eye-opening and vision problems may be present.

10. Normal birth weight.

11. Altered Sleep Pattern: Some may have excessive sleep tendencies, while others may have difficulty falling asleep.

Symptoms in Older Children and Adults: Most symptoms continue from the newborn stage.

1. Motor and Speech Problems: Mainly due to low muscle tone. Results in movement disorders, too.

2. Intellectual Disability: The affected individuals may also experience marked learning disabilities.

3. Uncontrolled seizures.

4. Gastrointestinal disturbances like constipation may be present.

5. Behavioral issues may be present. Some individuals suffering from PURA syndrome are also seen to be over-friendly or too shy, exhibiting behavioral issues. The loss of muscle tone is also present.

How Is It Diagnosed?

PURA syndrome is diagnosed using a comprehensive and multidisciplinary approach. Since the symptoms are similar to other conditions, it is crucial to get diagnosed early to start prompt care.

The diagnosis is done with the help of:

Clinical Assessments:

1. Formal Assessment: These help recognize speech delays and cognitive status.

2. An electroencephalogram measures the brain’s electrical activity and detects seizures and unusual patterns.

Imaging using magnetic resonance and computed tomography: These are used to assess any anomaly in the brain structure.

Assessment of eyes and electrodiagnostic vision tests to assess visual function.

Assessment of respiration, using a sleep study, to monitor breathing irregularities.

Assessment of feeding and swallowing to ensure safety and prevent food from being aspirated (entering the lungs).

Ultrasound scans of the heart and kidneys to rule out congenital malformations.

Bone density scans and vitamin D values are evaluated.

All these tests and assessments help understand the severity of the disease and the treatment required.

• Genetic Testing:

This is used to confirm the diagnosis after clinical assessments. This utilizes advanced technology called next-generation sequencing to recognize the mutations.

The main types include

1. Whole Exome Sequencing: This test analyzes all the protein-coding regions of the genes, most likely areas containing disease-causing mutations.

2. Whole Genome Sequencing: This more detailed test analyzes the entire genetic code, including coding and non-coding regions.

3. Parental Genetic Testing: Both parents' genetic patterns are assessed to determine whether the mutation is inherited or occurs spontaneously.

What Is the Differential Diagnosis?

Similar conditions to PURA syndrome include

1. Congenital Central Hypoventilation Syndrome: Breathing is markedly affected and can be differentiated from PURA using respiratory assessments and genetic testing.

2. Angelman Syndrome: It has an effect on the nervous system and is caused by disruption of a gene on chromosome 15.

3. Rett Syndrome: This syndrome involves loss of motor and communication skills and affects only females. Specific hand movements, scoliosis, and breathing difficulties are observed.

4. Prader-Willi Syndrome: This is caused by loss of function in chromosome 15. Individuals with this syndrome are known for distinct facial features and hyperphagia (a feeling of extreme hunger).

5. Spinal Muscular Atrophy: It is mainly characterized by muscle atrophy and weakness, caused by a gene mutation of the survival motor neuron protein.

6. Myotonic Dystrophy in the Newborn: Progressive muscle weakness and intellectual disability are seen in these cases.

7. Pitt-Hopkins Syndrome: This is characterized by severe breathing issues, gene mutation in different genes, and characteristic facial features (wide mouth with full lips).

How Is PURA Syndrome Inherited?

Most PURA syndromes are caused by new genetic mutations that are not inherited. However, in rare cases, a parent may carry the faulty gene without showing symptoms and pass it to their children. In such cases, it follows an autosomal dominant pattern (one copy of the altered gene is sufficient to cause disease). Genetic counseling is encouraged to help understand this aspect.

How to Manage the Disease?

There is no complete cure for PURA syndrome. However, early diagnosis and treatments are done to support specific symptoms based on the individual. Management involves ongoing medical care, supportive therapies, and support system networks.

The PURA syndrome treatment options include:

Medical Management:

It involved a combined effort from all specialties, like neurologists, genetic counselors, pediatricians, and parents or caregivers. When a team is involved, it helps the child get the best care.

1. Early Diagnosis and Intervention: This is very important for the best outcome.

2. Regular Medical Checkups: If there is any reflux, appropriate medications or adjustments in diet are made.

3. Anti-Seizure Medications: Epilepsy, commonly present in most individuals, is treated with the help of medication. In some cases, where there is no response to medications, a change of diet to a ketogenic (low-carbohydrate and high-fat) diet is shown to have better results.

4. Both nutritional and breathing support might be needed in severe cases. Breathing support may involve using supplemental oxygen if required.

2. Therapies:

A combination of consistent therapy sessions.

1. 1. Physical Therapy: This will help with muscle strength, posture, and balance to help in mobilization.

   2. Occupational Therapy: This is indicated to help the child become independent in life by toning fine motor skills and the ability to perform daily routine activities.

   3. Speech Therapy: It helps in communication and understanding the child's needs. If the child is struggling with verbal communication, tools like picture boards, sign language, and digital devices are utilized.

3) Support Groups:

1. An emotional and social support network provides inclusion in all daily activities.

2. Certain support groups can also emotionally support people and their loved ones. They offer a place to share experiences and connect with others facing the same challenges.

3. Family counseling may be needed, as it is a genetic disorder.

Prognosis:

Kids with PURA syndrome have a varied prognosis. Therapy and a supportive environment are much needed for a better prognosis. Also, they face a lot of physical and learning challenges throughout life. Early diagnosis, regular therapy, and a supportive family environment can help the child reach maximum potential.

Life Expectancy

There are limited studies on life expectancy, as this syndrome was only identified in 2014. However, based on current knowledge, many individuals with PURA syndrome can live into adulthood, mainly when seizures, breathing issues, and other complications are well managed.

Conclusion

PURA syndrome is rare but a critical condition to understand. Diagnosing it early and supporting the affected children can make a marked difference in their lives. The affected children face many challenges regularly, but getting the proper care and support ensures they can lead fulfilling lives. Learning about and understanding this rare syndrome helps provide them with the required care.

Keynote from iCliniq

Though rare, with limited studies on it, PURA syndrome still poses a challenge to clinicians and caregivers. With the proper support and care, it becomes easier to manage. If your child shows unusual developmental delays or you suspect a genetic condition, it is important to get a consultation. At iCliniq, our expert team can help navigate such rare conditions with clarity and care.