Multimodal Noninvasive Biomarker Characterization of Structural and Functional Alterations in ADSS1-Deficient...

Area of Science:

• Neurology
• Biomarkers
• Rare Diseases

Background:

• Adenylosuccinate synthase 1 (ADSS1)-deficient myopathy is an ultra-rare neuromuscular disorder causing progressive muscle dysfunction.
• Current understanding of ADSS1-deficient myopathy's full clinical spectrum, particularly in adults, requires further elucidation.

Purpose of the Study:

• To utilize noninvasive biomarkers for phenotyping motor skills, communication, and cognition in adults with ADSS1-deficient myopathy.
• To establish a multimodal research framework for sensitive and noninvasive assessment of neuromuscular dysfunction in ADSS1-deficient myopathy.

Main Methods:

• Multimodal evaluation of five adults with ADSS1-deficient myopathy and five healthy controls.
• Assessments included motor performance, speech/voice, cognition, patient-reported outcomes, electrical impedance myography (EIM), MRI, and plasma proteomics.
• Analysis focused on comparing ADSS1-deficient myopathy participants with healthy controls.

Main Results:

• ADSS1-deficient myopathy participants showed reduced motor performance (9-Hole Peg, grip strength), lower self-reported mobility, and impaired speech (asthenia, intelligibility, voice quality).
• Electrical impedance myography (EIM) indicated poorer muscle health, and MRI revealed intramuscular fat infiltration.
• Reduced plasma Neurotrophin-3 (NTF3) levels correlated with poorer motor function and EIM results.

Conclusions:

• Multimodal phenotyping effectively quantifies disease expression in ADSS1-deficient myopathy.
• Integrating EIM, motor, speech, imaging, and proteomic assessments provides a sensitive framework for monitoring neuromuscular dysfunction.
• This approach supports refined phenotyping and longitudinal disease monitoring for this ultra-rare condition.