A pilot investigation of muscle integrity in patients with ADSSL1 myopathy using electrical impedance myography.

INTRODUCTION/AIMS: ADSSL1 myopathy (OMIM 617030) is a recently discovered, congenital myopathic disease caused by a pathogenic variant in ADSSL1. ADSSL1 is an enzyme involved in the purine nucleotide process and facilitates the conversion of inosine monophosphate to adenosine monophosphate within myocytes. Electrical impedance myography (EIM) is a portable, non-invasive, and cost-effective method for characterizing muscle integrity. Three ADSSL1 patients are presented in whom characterization of muscle integrity using EIM was performed. METHODS: A 15-y-old male, 20-y-old female, and 63-y-old male each with a pathogenic variant in ADSSL1 [c.901G > A] as well as three, age-gender matched healthy controls (HCs) were enrolled. Study participants were phenotyped using a virtual EIM procedure. RESULTS: ADSSL1 myopathy patients presented with variable onset of physical disability, disease progression, and severity of muscle weakness. Across multiple proximal and distal muscles groups and relative to HCs, ADSSL1 myopathy patients demonstrated lower phase and reactance values, while resistance was higher, which together indicated diseased muscle. DISCUSSION: EIM can provide a novel, non-invasive and objective biomarker to evaluate muscle integrity in patients with ADSSL1 myopathy. Combining EIM with musculoskeletal imaging and histologic assessments in follow-up studies may further inform on the pathophysiology of ADSSL1 myopathy.

Diminished muscle integrity in patients with fibrodysplasia ossificans progressiva assessed with at-home electrical impedance myography.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder involving skeletal dysplasia and heterotopic ossification (HO) of muscle and connective tissue. We aimed to define a novel biomarker in FOP that enables reliable assessment of musculoskeletal tissue integrity. Considering logistical difficulties that FOP patients often face, our goal was to identify an at-home biomarker technique. Electrical impedance myography (EIM) is a non-invasive, portable method that can inform on muscle health. 15 FOP patients (age 10-52) and 13 healthy controls were assessed. Using EIM, multiple muscle groups were characterized per participant in a 45-min period. The Cumulative Analogue Joint Involvement Scale (CAJIS) was implemented to determine mobility burden severity. We additionally evaluated physical activity levels via a Patient-Reported Outcomes Measurement Information System (PROMIS)-based questionnaire. Relative to controls, FOP patients demonstrated significantly lower regional and whole-body phase values at 50 kHz and 100 kHz, indicating more diseased muscle tissue. Lower whole-body phase and reactance values, and higher resistance values, were associated with greater FOP burden (CAJIS score range: 4-30) and lower physical activity levels at 50 kHz and 100 kHz. This study points to the potential utility of EIM as a clinical biomarker tool capable of characterizing muscle integrity in FOP.