Multiple symmetric lipomatosis: evidence for mitochondrial dysfunction.

Area of Science:

• Biochemistry
• Neurology
• Genetics

Background:

• Multiple symmetric lipomatosis (MSL) is a rare condition characterized by the excessive accumulation of benign adipose tumors.
• The underlying pathophysiology of MSL, particularly the role of cellular energy metabolism, remains incompletely understood.

Purpose of the Study:

• To investigate the presence and extent of mitochondrial dysfunction in patients diagnosed with multiple symmetric lipomatosis.
• To explore the potential link between mitochondrial abnormalities and the clinical manifestations of MSL.

Main Methods:

• Utilized electromyography, nerve conduction studies, and autonomic function tests to assess neurological involvement in MSL patients.
• Performed nerve and muscle biopsies for histological examination and measurement of mitochondrial enzyme activities.
• Analyzed mitochondrial DNA (mtDNA) for mutations, including the myoclonic epilepsy ragged red fibers (MERRF) point mutation and multiple deletions.

Main Results:

• Clinical and electrophysiological evidence of polyneuropathy was observed in a majority of MSL patients.
• Muscle biopsies revealed subsarcolemmal mitochondrial accumulation and decreased activity of key respiratory chain enzymes like cytochrome-c oxidase (COX) and succinic dehydrogenase (SDH).
• While one patient exhibited the MERRF point mutation, widespread mtDNA abnormalities were not consistently found.

Conclusions:

• Mitochondrial dysfunction, evidenced by reduced mitochondrial numbers and diminished enzyme function, is a significant feature in MSL.
• These mitochondrial deficits are proposed as a potential pathogenetic basis for both lipoma development and the multisystemic symptoms associated with MSL.