Two Brothers With ADSS1 Myopathy: A Report of Clinical, Radiological, and Autopsy Findings

Area of Science:

• Neurology
• Genetics
• Pathology

Background:

• ADSSL1 myopathy is an autosomal recessive muscle disease caused by variants in the ADSS1 gene.
• It typically presents with limb muscle weakness, potentially complicated by respiratory issues or cardiomyopathy.
• Previous reports suggest trunk and hip muscles are relatively spared.

Purpose of the Study:

• To analyze the phenotype of two siblings with ADSSL1 myopathy.
• To detail muscle imaging and autopsy findings in these patients.
• To compare findings with existing literature on ADSSL1 myopathy.

Main Methods:

• Analysis of two siblings with compound heterozygous pathogenic variants (c.781G>A/c.919delA) in ADSS1.
• Clinical phenotyping, including muscle imaging.
• Autopsy examination of affected muscles.

Main Results:

• Early involvement of cervical paraspinal, triceps brachii, forearm flexors, rectus abdominis, and gluteal muscles observed.
• Cardiomyopathy was a significant finding.
• Atrophy of paraspinal, gluteal, and adductor muscles was noted, contrasting with previous reports.
• Nemaline bodies were found in the diaphragm and myocardium, linked to respiratory failure and cardiomyopathy.

Conclusions:

• ADSSL1 myopathy can present with early and distinct muscle group involvement, including axial and proximal lower limb muscles.
• The presence of nemaline bodies in the diaphragm and myocardium is a novel finding in this condition.
• These cases provide valuable long-term follow-up data for ADSSL1 myopathy.