709 - Pediatric Rehabilitation Considerations in Mitochondrial Disease Caused by Rare Pathogenic MT-ATP6 Variant and MT-CO1 Variant of Uncertain Significance: A case report

Thursday, February 19, 2026

5:00 PM - 6:30 PM AST

Presenting Author(s)

KL

Kristina N. Ledbetter, DO

PGY-3 Resident Physician
UCF/HCA Physical Medicine & Rehabilitation Residency
clearwater, Florida, United States

Co-Author(s)

KH

Kendall Hulk, DO, DO

Physician
UCF/HCA Physical Medicine & Rehabilitation Residency
Pensacola, Florida, United States
SB

Susan Belcher, MD

Program Director
UCF/HCA Physical Medicine & Rehabilitation Residency
Pensacola, Florida, United States

Submitter(s)

KL

Kristina N. Ledbetter, DO

UCF/HCA
clearwater, Florida, United States

Case Diagnosis: Suspected primary Mitochondrial disease with MT-ATP6 and MT-CO1 gene variants leading to multisystemic dysfunction and functional challenges.

Case Description: 5-year old male with a history of preterm birth, hypotonia, lactic acidosis, eosinophilic esophagitis, poor weight gain with G-tube, ketonuria, and global developmental delay presented for outpatient pediatric rehab evaluation due to ongoing exercise intolerance, hypotonia, and fatigue. Prior genetic testing identified a rare variant m.9155A >G in MT-ATP6 gene (32% heteroplasmy) and separate variant of uncertain significance m.6243G >A in gene MT-CO1 (29% heteroplasmy). Family history was notable for one relative with same MT-CO1 variant, and another relative with hypotonia, developmental delay, feeding difficulties, and excessive sleepiness. Multiple prior brain MRIs were inconclusive. On evaluation, he demonstrated antigravity strength throughout, intact gross motor function, and hyporeflexia. He ambulates with ankle foot orthosis and has a left leg length discrepancy. He requires some activities of daily living supervision. He exhibits impairments in strength, gait, coordination, and cognitive function. Ongoing rehabilitation has been critical in maintaining function and development.

Discussions: Mitochondrial diseases prevalence in the pediatric population is about 0.02%. The most common mutation is MT-ATP6 which accounts for 40% of mitochondrial DNA-associated Leigh syndrome spectrum. The m.9155A >G variant is rare, only reported in isolated cases. The MT-CO1 gene accounts for < 5% of mitochondrial disease, variant m.6243G >A clinical relevance is undetermined due to limited pathogenetic evidence. The combination of a pathogenic variant of MT-ATP6 and a variant of uncertain significance MT-CO1 is novel and has not been previously reported. Pediatric rehabilitation plays a crucial role with rare variants due to the variable and unpredictable progress requiring ongoing evaluation and assessment of rehab goals.

Conclusions: This case signifies the importance of pediatric physiatry in the ongoing care of patients with mitochondrial disease, especially novel genetic combinations for long term functional outcomes and rehabilitation planning.