Mitochondrial Membrane Protein-Associated Neurodegeneration.

Authors

Gregory A, Hartig M, Prokisch H, Kmiec T, Hogarth P, Hayflick SJ.

Editors

In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K, editors.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
2014 Feb 27.

Excerpt

CLINICAL CHARACTERISTICS:

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is characterized initially by gait changes followed by progressive spastic paresis, progressive dystonia (which may be limited to the hands and feet or more generalized), neuropsychiatric abnormalities (e.g., emotional lability, depression, anxiety, impulsivity, compulsions, hallucinations, perseveration, inattention, and hyperactivity), and cognitive decline. Additional early findings can include dysphagia, dysarthria, optic atrophy, axonal neuropathy, parkinsonism, and bowel/bladder incontinence. Survival is usually well into adulthood. End-stage disease is characterized by severe dementia, spasticity, dystonia, and parkinsonism.

DIAGNOSIS/TESTING:

The diagnosis of MPAN is confirmed in individuals with biallelic pathogenic variants in C19orf12. (Although no non-molecular tests are able to reliably distinguish MPAN from other NBIA disorders, postmortem neuropathologic examination in individuals in whom molecular testing was not performed may help support the diagnosis of MPAN.)

MANAGEMENT:

Treatment of manifestations: Pharmacologic treatment of spasticity, dystonia, and parkinsonism; psychiatric treatment of significant neuropsychiatric symptoms; physical, occupational, speech, and other therapies as indicated. Nutritional supplements and gastric feeding as needed. Management of excessive secretions and aspiration risk with glycopyrrolate, transdermal scopolamine patch, and/or tracheostomy as indicated. Surveillance: Routine follow up by a neurologist for medication management and interval assessment of ambulation, speech, and swallowing (often done every 3-6 months, but may be annual for patients who are more stable). Monitoring of patients receiving dopaminergic drugs for parkinsonism for adverse neuropsychiatric effects, and monitoring of patients receiving dopamine antagonist agents for psychiatric symptoms for the development or worsening of parkinsonism. Annual ophthalmologic examination is recommended.

GENETIC COUNSELING:

MPAN is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified. (Note: Possible autosomal dominant inheritance in one family has been reported.)

PMID:24575447