Abstract Details

Title Adult-onset Leigh Syndrome: An analysis of the North American Mitochondrial Disease Consortium Database

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 11-017

Objective This analysis of Adult-Onset Leigh Syndrome (LS) patients from the North American Mitochondrial Disease Consortium (NAMDC) Registry aims to enhance clinical insights, improve diagnoses, and uncover potential modifiers

Background LS is a rare syndrome linked to defects in more than one hundred genes. Most LS patients develop subacute neurological deterioration or regression before age two years. The pathological and radiological hallmarks are the subacute necrotizing degeneration of basal ganglia, cerebellum, brainstem, and/or cervical spinal cord, frequently triggered by metabolic stress. A small group of patients develop central nervous system involvement later in life.

Design/Methods This retrospective study stemmed from a case of a twenty-five-year-old man with mild developmental delay and sensory-motor neuropathy admitted for worsening weakness. During his hospital stay, he developed a rapidly progressive encephalopathy and classic LS radiological findings. Intrigued by this observation, we interrogated the NAMDC registry to retrieve data from other adult-onset LS individuals. The registry contains demographic, manifestation, genetic, imaging, and biochemistry data from more than 2100 subjects enrolled from 17 centers in North America and Canada.

Results

We identified six subjects with onset of CNS manifestations after age 18. Most of the subjects had been involved of other organ systems preceding the CNS lesions. Four probands had pathogenic variants in nuclear-encoded mitochondria metabolism genes, one in mitochondrial DNA-encoded ATP synthase subunit gene, and one patient remained genetically undefined. The disease progression varied among the cohort, with probands harboring nuclear variants experiencing a slower course compared to the individual with a mitochondrial DNA defect, who suffered a rapid, progressive, and fatal deterioration.

Conclusions Our data show that mitochondrial patients with LS experience evolving and progressive phenotypes, and the presence of manifestations in other organs often precedes LS in adults, suggesting that clinicians should carefully avoid metabolic stressors known to precipitate neurodegeneration in subjects with the observed genetic variants.

Authors/Disclosures
Emanuele Barca, MD, PhD (Columbia University) PRESENTER	Dr. Barca has nothing to disclose.
Adam Kroopnick, MD (NYP)	Dr. Kroopnick has nothing to disclose.
Alexander Houck, MD	Dr. Houck has nothing to disclose.
Kiran Thakur, MD, FAAN (Columbia University College of Physicians and Surgeons)	Dr. Thakur has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Delve Bio.
Rachelle Dugue, MD, PhD	Dr. Dugue has nothing to disclose.
Zarazuela Zolkipli-Cunningham, MBChB (The Children's Hospital of Philadelphia, Human Genetics)	Dr. Zolkipli-Cunningham has nothing to disclose.
Marni Falk	No disclosure on file
Amy Goldstein (CHOP)	Amy Goldstein has received personal compensation in the range of $500-$4,999 for serving as a speaker with UMDF.
Matthew Demczko (Children's Hospital of Philadelphia)	No disclosure on file
Ralitza H. Gavrilova, MD (Mayo Clinic)	Dr. Gavrilova has nothing to disclose.
Austin Larson	No disclosure on file
Johan Van Hove	The institution of Johan Van Hove has received research support from CureARS, NIH, NKH Crusaders, Mito Foundation, Brodyn's Friends, Les Petits Bourdons, Maud & Vic NKH fund, Tucker's Titans, Mikaere foundation. Johan Van Hove has received intellectual property interests from a discovery or technology relating to health care.
Russell P. Saneto, DO, PhD (Seattle Childrens Hospital)	Dr. Saneto has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for REATA. Dr. Saneto has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GW Pharmaceuticals. The institution of Dr. Saneto has received research support from NIH. The institution of Dr. Saneto has received research support from Zogenix. The institution of Dr. Saneto has received research support from GW Pharmaceuticals.
Richard Buchsbaum	No disclosure on file
John L. Thompson, PhD (Columbia Univ School of Public Health)	The institution of Dr. Thompson has received research support from NIH.
Michio Hirano, MD, FAAN (Columbia University Medical Center)	Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Biopharma SRL. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precision Biosciences. Dr. Hirano has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Biopharma SRL. Dr. Hirano has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Apollo Communication. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Envision Communications. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ��ɫ��. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Cure SMA. Dr. Hirano has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Muscular Dystrophy Association. The institution of Dr. Hirano has received research support from UCB. The institution of Dr. Hirano has received research support from Cyclerion. The institution of Dr. Hirano has received research support from Astellas. The institution of Dr. Hirano has received research support from Tisento Therapeutics. The institution of Dr. Hirano has received research support from Stealth Biotherapeutics. The institution of Dr. Hirano has received research support from Abliva. Dr. Hirano has received intellectual property interests from a discovery or technology relating to health care. Dr. Hirano has received intellectual property interests from a discovery or technology relating to health care. Dr. Hirano has received personal compensation in the range of $0-$499 for serving as a Study Section Reviewer with NIH. Dr. Hirano has a non-compensated relationship as a Research Advisory Board member with Muscular Dystrophy Association that is relevant to AAN interests or activities. Dr. Hirano has a non-compensated relationship as a Scientific and Medical Advisory Board member with United Mitochondrial Disease Foundation that is relevant to AAN interests or activities. Dr. Hirano has a non-compensated relationship as a Scientific Advisory Board member with Barth Syndrome Foundation that is relevant to AAN interests or activities.

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