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Inborn errors of coenzyme A metabolism and neurodegeneration

  • Ivano Di Meo
  • Miryam Carecchio
  • Valeria Tiranti
Review

Abstract

Two inborn errors of coenzyme A (CoA) metabolism are responsible for distinct forms of neurodegeneration with brain iron accumulation (NBIA), a heterogeneous group of neurodegenerative diseases having as a common denominator iron accumulation mainly in the inner portion of globus pallidus. Pantothenate kinase-associated neurodegeneration (PKAN), an autosomal recessive disorder with progressive impairment of movement, vision and cognition, is the most common form of NBIA and is caused by mutations in the pantothenate kinase 2 gene (PANK2), coding for a mitochondrial enzyme, which phosphorylates vitamin B5 in the first reaction of the CoA biosynthetic pathway. Another very rare but similar disorder, denominated CoPAN, is caused by mutations in coenzyme A synthase gene (COASY) coding for a bi-functional mitochondrial enzyme, which catalyzes the final steps of CoA biosynthesis. It still remains a mystery why dysfunctions in CoA synthesis lead to neurodegeneration and iron accumulation in specific brain regions, but it is now evident that CoA metabolism plays a crucial role in the normal functioning and metabolism of the nervous system.

Notes

Acknowledgments

The support of Telethon GGP16234 to VT and of Mariani Foundation of Milan is gratefully acknowledged.

Author’s contribution

IDM: Drafting of the manuscript; VT: Conception and design; MC revising the clinical description; IDM, MC and VT: Revising of the manuscript.

Compliance with ethics guidelines

Conflict of interest

Ivano Di Meo declares that he has no conflict of interest.

Miryam Carecchio declares she has no conflict of interest.

Valeria Tiranti declares that she has no conflict of interest.

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Copyright information

© SSIEM 2018

Authors and Affiliations

  1. 1.Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani centre for the study of mitochondrial disorders in childrenFoundation IRCCS Neurological Institute C. BestaMilanItaly
  2. 2.Department of Child Neurology,Foundation IRCCS Neurological Institute C. BestaMilanItaly
  3. 3.Department of Medicine and Surgery, PhD Programme in Molecular and Translational MedicineUniversity of Milan BicoccaMonzaItaly

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