Throughout my career, I have kept a focused interest on inborn errors of energy metabolism, recognizing unusual patients through clinical observation, and using both biochemical and molecular approaches to define disease entities. For the first ten years, I was an "enzyme defect hunter", and I was lucky enough to document carnitine palmitoyltransferase (CPT) deficiency in two brothers with exercise intolerance and recurrent myoglobinuria, the first error of fatty acid oxidation to be recognized in humans. Similar detective work in other patients with recurrent myoglobinuria led me to discover two defects of terminal glycolysis, phosphoglycerate mutase (PGAM) deficiency, and phosphoglycerate kinase (PGK) deficiency. More recent work from my group has defined the molecular bases of myophosphorylase, phosphofructokinase (PFK), PGAM, and PGK deficiencies.
In the early 1970s, my interest turned to mitochondrial myopathies, and I was lucky enough to learn mitochondrial bioenergetics in the laboratories of Britton Chance and C.P. Lee at the University of Pennsylvania. With them, I studied the second patient with Luft syndrome, the prototypical (though also the rarest) mitochondrial disease. At Columbia University, I set up biochemical tests to study respiratory chain enzymes in frozen muscle biopsies, which started pouring in from all over the world. Thus, in 1980 and in 1983, I described two distinct forms of cytochrome oxidase (COX)-deficient myopathy, and, in 1987, I helped define COX-deficient Leigh syndrome. Since 1983, I direct a multidisciplinary group of "mitochondriacs" that is recognized as one of the best in the world. Our contributions include: the association of single mtDNA deletions with Kearns-Sayre syndrome (KSS) and progressive external ophthalmoplegia (PEO); the description of about 30 novel pathogenic point mutations in mtDNA; the concept of mtDNA depletion; the association of somatic mutations in mtDNA protein-coding genes with exercise intolerance.
Thus, although I started as a myologist, my studies of mitochondrial diseases have taken me back to the brain. Because the brain is so crucially dependent on oxidative metabolism, mitochondrial dysfunction almost always impairs brain function and often causes mental retardation. Our interest in the relationship between mitochondrial disorders and mental retardation has been recognized by the National Institute for Child Health and Human Development (NICHD), which supports a Program Project under my direction entitled "Mitochondrial Encephalomyopathies and Mental Retardation."
| 1964-68 |
Instructor, Institute of General Pathology, University of Padova, Italy |
| 1969-72 |
Postdoctoral Fellow, Dept. of Neurology, University of Pennsylvania, Philadelphia, PA.
Instructor, Dept. Neurology, University of Pennsylvania |
| 1972-74 |
Assistant Professor, Dept. Neurology, University Pennsylvania |
| 1974-78 |
Associate Professor, Neurological Institute, Columbia University, New York |
| 1978-99 |
Co-Director, H. Houston Merritt Clin. Res. Center for Muscular Dystrophy and Related Diseases |
| 1999- |
Director, H. Houston Merritt Clin. Res. Center for Muscular Dystrophy and Related Diseases |
| 1978- |
Professor, Neurological Institute, Columbia University, New York |
| 1991- |
Lucy G. Moses Professor of Neurology |
| 1984-85 |
Dean's Distinguished Lecturer in the Clinical Sciences, Columbia University College
of Physicians and Surgeons |
| 1989 |
George Cotzias Memorial Lecturer, American Academy of Neurology |
| 1989 |
Bernard Sachs Lecturer, Child Neurology Society |
| 1991 |
Lucy G. Moses Professor of Neurology, December |
| 1992 |
John Keith Barlow Memorial Lecturer, Massachusetts General Hospital, Boston |
| 1992 |
Honorary Member, Spanish Society of Neurology |
| 1993 |
Duchenne-Erb Award for 1993 (shared wit Dr. Marinos Dalakas), Deutsche
Gesellschaft fur Muskelkranke (DGM), Wurzburg, Germany |
| 1993 |
Soriano Lecturer, 119th Annual Meeting of the American Neurological Association,
San Francisco, CA |
| 1994 |
"Antonio Feltrinelli" National Award for Medicine from the National "Lincei"
Academy, Rome |
| 1995 |
Jacobson Visiting Lecturer, Faculty of Medicine, University of Newcastle, Newcastle
upon Tyne, U.K. |
| 1995 |
Hower Award, Child Neurology Society |
| 1996 |
Honorary Member, Australian Association of Neurologists |
| 1996 |
Honorary Member, Japanese Society for Inborn Errors of Metabolism |
| 1998 |
Honorary Member, Spanish Society of Pediatric Neurology |
| 1998 |
"Insignia de Ouro" (Golden Seal) of the University of Santiago de Compostela, Spain |
| 1999 |
Docteur Honoris Causa, Université de la Mediterranée, Marseille, France |
| 1999 |
Honorary Member, Chilean Society of Child Psychiatry & Neurology |
| 2000 |
Robert Guthrie Award from the American Association on Mental Retardation (AAMR), Washington, DC |
| 2002 |
Member, Institute of Medicine of the National Academy of Sciences |
- DiMauro S, Melis-DiMauro P. Muscle carnitine palmityltransferase deficiency and myoglobinuria. Science 1973;182:929-931.
- DiMauro S, Miranda AF, Khan S, Gitlin K, Friedman R. Human muscle phosphoglycerate mutase deficiency: A newly discovered metabolic myopathy. Science 1981;212:1277-1279.
- Tsujino S, Shanske S, DiMauro S. Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease). New Engl J Med 1993;329:241-245.
- Moraes CT, Shanske S, Tritschler HJ, Aprille JR, Andreetta F, Bonilla E, Schon EA, DiMauro S. Mitochondrial DNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. Am J Hum Genet 1991;48:492-501.
- Andreu AL, Hanna MG, Reichmann H, Bruno C, Penn AS, Tanji K, Pallotti F, Iwata S, Bonilla E, Lach B, Morgan-Hughes J, DiMauro S. Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA. New Engl J Med 1999;341:1037-1044.
- DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. New Engl J Med 2003;348:2656-2668.
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