518 - When Microtubules Misbehave: De Novo TUBA4A Variant in Spastic Paraplegia

Thursday, February 19, 2026

5:00 PM - 6:30 PM AST

Presenting Author(s)

NS

Nadia Selod, BS

Medical Student
The Joe R. & Teresa Lozano Long School of Medicine
Fort Worth, Texas, United States
OR

Omid Rahmanian, DO

Resident
UT Health San Antonio
Allen, Texas, United States

Co-Author(s)

MV

Monica Verduzco-Gutierrez, MD

Professor and Chair, dept of Rehab Medicine
UT Health San Antonio
San Antonio, Texas, United States

Submitter(s)

NS

Nadia Selod, BS

The Joe R. & Teresa Lozano Long School of Medicine
Fort Worth, Texas, United States

Case Diagnosis: We report the case of a 35 y/o male with childhood-onset progressive spastic paraplegia, refractory to multiple oral antispasticity agents, ultimately managed with intrathecal baclofen (ITB) therapy. Despite extensive genetic and metabolic workup, a definitive molecular diagnosis remained elusive; however, a rare variant of uncertain significance (VUS) in the TUBA4A gene was identified.

Case Description: A 35 y/o ambidextrous male presented for evaluation and management of progressive lower extremity spasticity and paraplegia. Symptoms began at age 7, and he became wheelchair dependent in his late 20s. His severe spasticity was accompanied by pain, weakness, and paresthesia in the soles. He was previously treated with oral baclofen, which failed to provide relief. Exam showed increased tone and severe spasticity in the lower extremities. Family history was negative. Genetic testing revealed a VUS in the TUBA4A gene. Due to poor response to oral baclofen, ITB was placed. After catheter malfunction, a new one was installed.

Discussions:
Pathogenic variants in TUBA4A, located on chromosome 2, have been most commonly associated with ALS and frontotemporal dementia . However, the phenotypic spectrum of TUBA4A mutations has expanded to include hereditary spastic paraplegia and cerebellar ataxia. To date, only 12 cases of TUBA4A missense mutations linked to spasticity and cerebellar ataxia have been reported, with five identified as de novo variants.

Conclusions:
This case adds to the growing body of evidence that TUBA4A mutations, while classically associated with ALS and FTD, can also underlie hereditary spastic paraplegia. The rarity of this patient’s presentation being the only known HSP case with a de novo TUBA4A mutation of its kind in the United States underscores the need for further research. This case emphasizes the importance of thorough genetic testing, multidisciplinary care, and monitoring for device related complications in the management of complex spastic paraplegia syndromes.