European journal of neurology
September 1, 2026 · via Europe PMC
TUBA4A Pathogenic Variant Manifesting With Adulthood-Onset Genetic Myasthenic Syndrome, Myopathy, and Infertility.
Milone M, Nicolau S, Niu Z, Liewluck T, Sorenson EJ, Shen XM, Harper CM, Litchy WJ.
AI summary — for doctors, generated from the abstract only
A TUBA4A pathogenic variant caused an adult-onset treatable myasthenic syndrome with myopathy and infertility in one patient.
What was studied
A case report with clinical, electrophysiological, biopsy and transcriptomic evaluation of a 53-year-old woman with a TUBA4A p.Glu284Lys variant.
Key findings
- Proximal fatigable weakness from her mid-30s with negative MG antibodies
- RNS decrement improved with 3,4-DAP; facilitation in trapezius
- Improved with 3,4-DAP and albuterol
Clinical relevance
Expands the TUBA4A phenotype and suggests a treatable component; single case.
Who should care
Limitations
Single case report.
TUBA4A variants can cause treatable myasthenic syndromes.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Objectives
TUBA4A pathogenic variants are associated with ALS, frontotemporal dementia, spastic ataxia, spasticity, ataxia, Parkinson's disease, female infertility, macrothrombocytopenia, and myopathy. Four recently reported patients with TUBA4A neonatal/childhood onset myopathy had also a decrement on repetitive nerve stimulation (RNS), but such a finding was not further characterized. We describe a patient with a TUBA4A pathogenic variant with adulthood-onset genetic myasthenic syndrome accompanied by myopathy and infertility to highlight the neuromuscular junction defect as the main feature of the patient's phenotype.
Methods
We reviewed the patient's clinical and laboratory findings and performed transcriptomic analysis on the patient's muscle.
Results
A 53-year-old woman with infertility of unknown etiology manifested fatigability and proximal upper limb muscle weakness in her mid-30s, followed by lower limb involvement. Her examination showed proximal muscle weakness and fatigability but spared facial muscles. CK values were mildly elevated. Anti-AChR, MuSK, P/Q-type calcium channel, and LRP4 antibodies were absent. 2 Hz RNS showed decrement (-14% to -48%) in limb muscles that improved with 3,4-dyaminopyridine (3,4-DAP). Facilitation (231%) occurred in the trapezius. Muscle biopsy showed patchy loss of oxidative enzyme reactivity and no C5b9 or IgG at neuromuscular junctions. Whole genome sequencing identified a heterozygous known TUBA4A pathogenic variant (c.850G>A, p.Glu284Lys). Patient improved with 3,4-DAP and albuterol.
Discussion
TUBA4A p.Glu284Lys can lead to treatable myasthenic syndrome with postsynaptic and likely presynaptic involvement, as suggested by the patient's electrophysiological findings and response to therapy. This patient expands the TUBA4A-disorder spectrum to include overlapping myasthenic syndrome-myopathy and shows that neuromuscular disease and infertility can occur within the same patient.
DOI
10.1111/ene.70753
PMID
42725680
PMCID
PMC13564105
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
Want more like this?
Browse more from the feed. A free account unlocks the full feed, saving and communities.
Back to the research feed