Clinical Guidance
Mitochondrial membrane protein-associated neurodegeneration (MPAN) is characterized initially by gait changes followed by progressive spastic paresis, progressive dystonia, neuropsychiatric abnormalities, and cognitive decline. Additional early findings can include dysphagia, dysarthria, optic atrophy, axonal neuropathy, parkinsonism, and bowel/bladder incontinence. Onset of MPAN typically occurs in childhood (3-16 years, considered juvenile onset) to early adulthood (17-24 years, considered adult onset), but onset has been reported as late as age 55 years . Among affected sibs the age of onset is similar. The disease course is similar across age groups, with the exception of some adult-onset, rapidly progressive cases described below. Individuals with MPAN learn to walk and are usually mobile into early adulthood . The most common presenting feature is impaired gait. Early gait changes are typically followed by the onset of progressive spastic paresis. Some individuals present with vision impairment associated with optic atrophy, which is more common in childhood-onset than adult-onset MPAN. The progression of MPAN is usually slow with survival well into adulthood. However, rare individuals have had abrupt adult onset and rapid progression . The terminal stages of MPAN are characterized by severe dementia, spasticity, dystonia, and parkinsonism. Affected individuals are no longer ambulatory; communication is limited due to dysarthria and cognitive decline. Weight loss and bowel and/or bladder incontinence are common. Persons with advanced disease may have stereotypic hand or head movements with alterations in consciousness that do not appear to be manifestations of seizures. Death typically occurs secondary to complications such as aspiration pneumonia. Fewer than 200 affected individuals have been described to date; thus, the phenotypic spectrum of MPAN is likely to broaden as more affected individuals are described. The phenotypes associated with autosomal recessive (AR) MPAN and autosomal dominant (AD) MPAN are indistinguishable . Table 2. Select Features of Mitochondrial Membrane Protein-Associated Neurodegeneration
