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Mitochondrial membrane protein-associated neurodegeneration

Reviewed April 2014

What is mitochondrial membrane protein-associated neurodegeneration?

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a disorder of the nervous system. The condition typically begins in childhood or early adulthood and worsens (progresses) over time.

MPAN commonly begins with difficulty walking. As the condition progresses, affected individuals usually develop other movement problems, including muscle stiffness (spasticity) and involuntary muscle cramping (dystonia). Many people with MPAN have a pattern of movement abnormalities known as parkinsonism. These abnormalities include unusually slow movement (bradykinesia), muscle rigidity, involuntary trembling (tremors), and an inability to hold the body upright and balanced (postural instability).

Other neurological problems that occur in individuals with MPAN include degeneration of the nerve cells that carry visual information from the eyes to the brain (optic atrophy), which can impair vision; problems with speech (dysarthria); difficulty swallowing (dysphagia); and, in later stages of the condition, an inability to control the bowels or the flow of urine (incontinence). Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, mood swings, hyperactivity, and depression.

MPAN is characterized by an abnormal buildup of iron in certain regions of the brain. Because of these deposits, MPAN is considered part of a group of conditions known as neurodegeneration with brain iron accumulation (NBIA).

How common is mitochondrial membrane protein-associated neurodegeneration?

MPAN is a rare condition that is estimated to affect less than 1 in 1 million people.

What genes are related to mitochondrial membrane protein-associated neurodegeneration?

Mutations in the C19orf12 gene cause MPAN. The protein produced from this gene is found in the membrane of cellular structures called mitochondria, which are the energy-producing centers of the cell. Although its function is unknown, researchers suggest that the C19orf12 protein plays a role in the maintenance of fat (lipid) molecules, a process known as lipid homeostasis.

The gene mutations that cause this condition lead to an altered C19orf12 protein that likely has little or no function. It is unclear how these genetic changes lead to the neurological problems associated with MPAN. Researchers are working to determine whether there is a link between problems with lipid homeostasis and brain iron accumulation and how these abnormalities might contribute to the features of this disorder.

Related Gene(s)

Changes in this gene are associated with mitochondrial membrane protein-associated neurodegeneration.

  • C19orf12

How do people inherit mitochondrial membrane protein-associated neurodegeneration?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of mitochondrial membrane protein-associated neurodegeneration?

These resources address the diagnosis or management of mitochondrial membrane protein-associated neurodegeneration and may include treatment providers.

  • Gene Review: Mitochondrial Membrane Protein-Associated Neurodegeneration (
  • Gene Review: Neurodegeneration with Brain Iron Accumulation Disorders Overview (
  • Genetic Testing Registry: Neurodegeneration with brain iron accumulation 4 (
  • Spastic Paraplegia Foundation: Treatments and Therapies (

You might also find information on the diagnosis or management of mitochondrial membrane protein-associated neurodegeneration in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about mitochondrial membrane protein-associated neurodegeneration?

You may find the following resources about mitochondrial membrane protein-associated neurodegeneration helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for mitochondrial membrane protein-associated neurodegeneration?

  • mitochondrial membrane protein-associated neurodegeneration due to C19orf12 mutation
  • mitochondrial protein-associated neurodegeneration
  • MPAN
  • NBIA4
  • neurodegeneration with brain iron accumulation 4

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about mitochondrial membrane protein-associated neurodegeneration?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding mitochondrial membrane protein-associated neurodegeneration?

atrophy ; autosomal ; autosomal recessive ; bradykinesia ; cell ; dementia ; depression ; difficulty swallowing ; dysarthria ; dysphagia ; dystonia ; gene ; homeostasis ; hyperactivity ; incontinence ; inherited ; involuntary ; involuntary trembling ; iron ; lipid ; mitochondria ; mutation ; nervous system ; neurological ; optic atrophy ; paraplegia ; parkinsonism ; protein ; recessive ; spasticity

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Dogu O, Krebs CE, Kaleagasi H, Demirtas Z, Oksuz N, Walker RH, Paisán-Ruiz C. Rapid disease progression in adult-onset mitochondrial membrane protein-associated neurodegeneration. Clin Genet. 2013 Oct;84(4):350-5. doi: 10.1111/cge.12079. Epub 2013 Jan 21. (
  • Gene Review: Mitochondrial Membrane Protein-Associated Neurodegeneration (
  • Hartig M, Prokisch H, Meitinger T, Klopstock T. Mitochondrial membrane protein-associated neurodegeneration (MPAN). Int Rev Neurobiol. 2013;110:73-84. doi: 10.1016/B978-0-12-410502-7.00004-1. Review. (
  • Hartig MB, Iuso A, Haack T, Kmiec T, Jurkiewicz E, Heim K, Roeber S, Tarabin V, Dusi S, Krajewska-Walasek M, Jozwiak S, Hempel M, Winkelmann J, Elstner M, Oexle K, Klopstock T, Mueller-Felber W, Gasser T, Trenkwalder C, Tiranti V, Kretzschmar H, Schmitz G, Strom TM, Meitinger T, Prokisch H. Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am J Hum Genet. 2011 Oct 7;89(4):543-50. doi: 10.1016/j.ajhg.2011.09.007. (
  • Hogarth P, Gregory A, Kruer MC, Sanford L, Wagoner W, Natowicz MR, Egel RT, Subramony SH, Goldman JG, Berry-Kravis E, Foulds NC, Hammans SR, Desguerre I, Rodriguez D, Wilson C, Diedrich A, Green S, Tran H, Reese L, Woltjer RL, Hayflick SJ. New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN. Neurology. 2013 Jan 15;80(3):268-75. doi: 10.1212/WNL.0b013e31827e07be. Epub 2012 Dec 26. (
  • Schulte EC, Claussen MC, Jochim A, Haack T, Hartig M, Hempel M, Prokisch H, Haun-Jünger U, Winkelmann J, Hemmer B, Förschler A, Ilg R. Mitochondrial membrane protein associated neurodegenration: a novel variant of neurodegeneration with brain iron accumulation. Mov Disord. 2013 Feb;28(2):224-7. doi: 10.1002/mds.25256. Epub 2012 Nov 19. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: April 2014
Published: February 1, 2016