Rebecca Hsu1, Hristelina Ilieva2
1Thomas Jefferson University, Department of Neurology, 2ALS Weinberg Clinic
Objective:
We report a patient with c.1246C>T (p.R416C) heterozygous variant on the ATL1 gene causing a complicated form of hereditary spastic paraparesis (HSP) who had an early age of onset but had non-progressive disease until a rapid decline at age 57 after bariatric surgery.
Background:
In 2018, a Chinese research group found a the same p.R416C mutation in ATL1 in a family with complicated HSP. The affected members of the family had a young age of onset, but intriguingly the mother of the proband carrying the mutation remained asymptomatic. This suggests a modulator gene or epigenetic factors contributing to the presentation of HSP.
Results:
The patient of interest had symptoms starting at age 5. His weakness first manifested with clumsy walking and difficulty running. Patient reports that his motor deficit, notably affecting only his lower extremity muscles diffusely, plateaued at age 10. He did not have any major ambulatory dysfunction until age 57. At age 57, he underwent bariatric surgery and lost approximately 130 pounds. Since then, he noticed worsening lower extremity strength with decreased ability to ascend and descend the stairs to walk longer distances. Our case report suggests bariatric surgery as a possible trigger for the rapid decline in a patient with otherwise stable disease.
Conclusions:
Bariatric surgery can cause nutritional deficiencies that can affect nerve health, but our patient did not have identifiable nutritional deficiencies. Research into bariatric surgery has shown that obesity-related epigenome is altered after bariatric surgery via different patterns of DNA methylation. The epigenetic reprogramming may have altered the phenotypic expression of this patient’s genetic mutation, promoting disease progression. For many years, the range of phenotypic expressions among patients with HSP has puzzled clinicians. More research will be needed to evaluate variability in epigenomic mechanisms contributing to the variability in phenotype among patients with HSP.