Deficiency of beta-propeller protein-associated neurodegeneration

Summary about Disease


Beta-propeller protein-associated neurodegeneration (BPAN) is a rare, slowly progressive neurological disorder characterized by iron accumulation in the brain, particularly in the basal ganglia. It is a type of neurodegeneration with brain iron accumulation (NBIA). It typically presents with developmental delay, intellectual disability, and progressive dystonia (involuntary muscle contractions).

Symptoms


Developmental delay (speech, motor skills)

Intellectual disability

Dystonia (involuntary muscle contractions, abnormal postures)

Parkinsonism (tremor, rigidity, slow movement)

Seizures

Visual impairment (optic atrophy)

Behavioral problems (aggression, self-injury, autism spectrum disorder features)

Progressive cognitive decline

Axonal neuropathy

Iron accumulation in the brain (visible on MRI)

Causes


BPAN is caused by mutations in the WDR45 gene. This gene provides instructions for making a protein that is part of a complex involved in autophagy (cellular "housekeeping"). Mutations in *WDR45* disrupt autophagy, leading to the accumulation of cellular waste products, including iron, in the brain. BPAN is inherited in an X-linked dominant pattern.

Medicine Used


There is no cure for BPAN, and treatment focuses on managing symptoms. Medications used may include:

Medications for dystonia: such as trihexyphenidyl, baclofen, or botulinum toxin injections.

Medications for parkinsonism: such as levodopa (although response is often limited).

Antiepileptic drugs: to control seizures.

Medications for behavioral problems: such as antidepressants or antipsychotics.

Iron chelators: such as deferiprone, are sometimes used, although their effectiveness in BPAN is still under investigation.

Physical therapy, occupational therapy, and speech therapy: to help maintain motor function, improve daily living skills, and address communication difficulties.

Is Communicable


No, BPAN is not communicable. It is a genetic disorder caused by a gene mutation and cannot be spread from person to person.

Precautions


Since BPAN is a genetic disorder, there are no specific precautions to prevent acquiring it. Genetic counseling is recommended for families with a history of BPAN who are considering having children. Monitoring and management of symptoms, such as seizures and dystonia, are important for individuals with BPAN to improve their quality of life and prevent complications.

How long does an outbreak last?


BPAN is not an infectious disease and does not have outbreaks. It is a chronic, progressive condition that lasts a lifetime.

How is it diagnosed?


Diagnosis of BPAN typically involves:

Clinical evaluation: Assessment of symptoms, neurological examination, and family history.

Brain MRI: To visualize iron accumulation in the basal ganglia, particularly the substantia nigra.

Genetic testing: To identify mutations in the WDR45 gene.

Timeline of Symptoms


Early childhood: Developmental delay (speech, motor skills), intellectual disability.

Childhood/Adolescence: Dystonia, parkinsonism, seizures, behavioral problems.

Adulthood: Progressive cognitive decline, visual impairment, worsening motor symptoms, axonal neuropathy. The progression and severity of symptoms can vary among individuals.

Important Considerations


BPAN is a complex disorder with a wide range of symptoms and severity.

Early diagnosis and intervention are important to optimize outcomes.

A multidisciplinary approach involving neurologists, geneticists, therapists, and other specialists is essential for comprehensive care.

Genetic counseling is important for families affected by BPAN.

Research is ongoing to better understand BPAN and develop new treatments.