MPAN

Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN)

GENE: C19orf12;
INHERITANCE: Autosomal recessive or dominant;
ONSET: Childhood to early adulthood;
SYMPTOMS: Dystonia, spasticity, cognitive decline, and parkinsonism;
NOTES: MPAN is characterized by early-onset dystonia and spasticity, progressing to cognitive decline.

Overview

Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) is a rare, inherited neurological disorder that is part of the NBIA spectrum. MPAN is characterized by progressive iron accumulation in specific regions of the brain, particularly the basal ganglia, which leads to movement difficulties, cognitive decline, and other neurological symptoms.

Although MPAN is rare, understanding its progression and genetic basis is key to early diagnosis and supportive care.

Genetics

MPAN is primarily inherited in an autosomal recessive manner, meaning a child must inherit two copies of the altered C19orf12 gene (one from each parent) to develop the disorder. In some cases, an autosomal dominant inheritance pattern has also been reported.

Parents who are carriers typically do not show symptoms, but there is a 25% chance for a child to be affected if both parents carry a mutation. Genetic testing is crucial for confirming diagnosis, identifying carriers, and supporting family planning.

Symptoms & Clinical Features

The hallmark symptoms of MPAN include:

Movement Disorders: Dystonia, spasticity, parkinsonism, and difficulties with coordination.
Cognitive Decline: Progressive reduction in intellectual functioning and memory.
Speech & Swallowing Difficulties: Dysarthria and dysphagia are common as the disorder progresses.
Visual Symptoms: Some individuals may experience optic atrophy.
Behavioral Changes: Anxiety, depression, and emotional instability may develop.

Symptoms usually begin in childhood or early adulthood, and progression can vary between individuals.

Diagnosis

MPAN is diagnosed based on clinical evaluation, brain imaging, and genetic testing for mutations in the C19orf12 gene. Brain MRI often shows characteristic iron accumulation in the globus pallidus and substantia nigra.

Early diagnosis allows families to access therapies, supportive care, and monitoring for complications.

Management & Care

There is currently no cure for MPAN, and treatment focuses on managing symptoms and improving quality of life. This may include:

Medications to manage dystonia, spasticity, or parkinsonism.
Physical, occupational, and speech therapy.
Supportive devices such as walkers, wheelchairs, or communication aids.
Regular monitoring by neurologists and other specialists.

Resources

1. NBIA Disorders Association – MPAN
2. Childhood Dementia Organization.
3. Genetic counseling and testing centers specializing in NBIA disorders.