The Diagnosis of Acquired, Late-Onset Nemaline Myopathy Should Not Be Made Before Primary Nemaline Myopathy Has Been Excluded

Correspondence We were interested to read the article by Narwal et al.1 about a 60-year-old man with acquired, late-onset nemaline myopathy due to monoclonal gammopathy of undetermined significance (MGUS). The patient clinically presented with proximal quadriparesis.1 Electromyography was myopathic and muscle biopsy showed nemaline rods in the muscle fibers.1 The patient received intravenous immunoglobulins with success.1 The study is noteworthy, but some points need to be discussed. The first point is that no genetic testing was performed.1 Even if the family history is negative for nemaline myopathy, it would have been imperative to rule out primary nemaline myopathy. A negative family history of the disease does not rule out the possibility that the index patient has a sporadic mutation in NEB, ACTA1, or TPM3, TPM2, TNNT1, or MYO18B. Mutations in NEB account for 50% of cases, and mutations in ACTA1 account for 15-25% of cases. The late onset of clinical manifestations does not rule out the possibility that the nemaline myopathy was congenital but initially subclinical. Therefore, the first differential diagnosis of sporadic late-onset nemaline myopathy is hereditary nemaline myopathy. Acquired nemaline myopathy can only be diagnosed once hereditary nemaline myopathy has been ruled out. The second issue is that the index patient has not been prospectively evaluated for cardiac disease in nemaline myopathy.1 Cardiac manifestations of nemaline myopathy include dilated cardiomyopathy, hypertrophic cardiomyopathy, and cardiac septal defect, all of which can be complicated by heart failure.2 Since cardiac disease in nemaline myopathy is a major determinant of disease outcome and is potentially treatable, it is imperative that all patients with nemaline myopathy are also screened for cardiac disease to avoid missing the start of cardiac treatment. Thirdly, respiratory muscle strength was not measured.1 As nemaline myopathy can also affect the axial and respiratory muscles,3 measurement of vital capacity, FEV1, and O2 saturation is essential. Was there any evidence of involvement of the repertory muscles in the disease in the index patient? The fourth point is that MGUS is characterized by the production of a monoclonal gamma globulin.4 Surprisingly, the index patient had an abnormal protein within the beta band of protein electrophoresis, which was interpreted as an M-gradient.1 This discrepancy should be clarified. In addition, MGUS often manifests as a demyelinating polyneuropathy.4 Was there evidence of MGUS-associated neuropathy in the index patient? Finally, the patient also had dysphagia. Was this due to the involvement of the striated or smooth pharyngeal muscles? Availability of data and material All data are available from the corresponding author Author contribution JF was responsible for the design and conception, discussed available data with coauthors, wrote the first draft, and gave final approval. GM: contributed to literature search, discussion, correction, and final approval. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.