Recessive mutations in the mitochondrial copper-binding protein SCO2, cytochrome c oxidase (COX) assembly protein, have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency. Significantly expanding the known phenotypic spectrum, we identified compound heterozygous variants in SCO2 in two unrelated patients with axonal polyneuropathy, also known as Charcot-Marie-Tooth disease type 4. Different from previously described cases, our patients developed predominantly motor neuropathy, they survived infancy, and they have not yet developed the cardiomyopathy that causes death in early infancy in reported patients. Both of our patients harbour missense mutations near the conserved copper-binding motif (CXXXC), including the common pathogenic variant E140K and a novel change D135G. In addition, each patient carries a second mutation located at the same loop region, resulting in compound heterozygote changes E140K/P169T and D135G/R171Q. Patient fibroblasts showed reduced levels of SCO2, decreased copper levels and COX deficiency. Given that another Charcot-Marie-Tooth disease gene, ATP7A, is a known copper transporter, our findings further underline the relevance of copper metabolism in Charcot-Marie-Tooth disease.

Liver transplantation has been used in treatment of transthyretin amyloidosis, and some patients undergo domino liver transplantation (DLT) with explanted liver being transplanted to another patient with liver failure as the liver is otherwise usually functionally normal. Until end of 2015, there were 1154 DLT performed worldwide. DLT for transthyretin amyloidosis is associated with the risk of developing de novo systemic amyloidosis and amyloid neuropathy, and the risk may be greater with some non-Val30Met mutations. De novo amyloid neuropathy has been described in up to 23% of transplant recipients. Neuropathy may be preceded by asymptomatic amyloid deposition in various tissues and symptoms of neuropathy started after a median of 7 years following DLT (5.7 ± 3.2 years; range 2 mo to 10 years). Typical initial symptoms include neuropathic pain and sensory loss, while dysautonomia usually starts later. Progression of neuropathy may necessitate liver re-transplantation, and subsequent improvement of neuropathy has been reported in some patients. Explant allograft recipients need close monitoring for signs of systemic amyloidosis, neuropathy and dysautonomia as progressive symptoms may require re-transplantation.

Lambert–Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder, and dermatomyositis (DM) is an idiopathic inflammatory myopathy. LEMS and DM are uncommon conditions that can present similarly and are often associated with autoantibodies. Concomitant LEMS and DM have only been reported a few times, and most of those cases were paraneoplastic. We present the first reported case of a patient with antivoltage gated calcium channel antibody positive LEMS who subsequently developed DM with antitranscription intermediary factor 1-gamma (anti–TIF1-γ) antibodies. Interestingly, both conditions occurred without evidence of malignancy. This diagnosis of LEMS and DM with characteristic clinical, electrodiagnostic, and histopathological evidence led to a beneficial modification of the patient's therapeutic regimen. Due to the fact that overlapping concurrent neuromuscular conditions are rare, a high clinical suspicion is needed to identify, evaluate (including appropriate cancer screenings), and appropriately treat these patients.

Hereditary transthyretin amyloidosis (hATTR) is a rare cause of severe neuropathy, typically with progressive sensorimotor and autonomic manifestations. The clinical course is marked by progressive worsening with typical survival of 7–11 years following the onset of symptoms. The phenotype may resemble other types of neuropathy, and dysautonomia may be absent at onset delaying the diagnosis. Two medications were recently approved for treatment of hATTR neuropathy in the United States and more may follow. Three major phenotypes of hATTR include neuropathic, cardiac, and mixed. Diagnostic clues include “red-flag” symptoms reflecting typical multisystem involvement, often presenting with cardiomyopathy, gastrointestinal dysmotility, or kidney insufficiency. We present a case series of 4 patients with late-onset hATTR neuropathy who were initially diagnosed with vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy to illustrate diagnostic challenges encountered with hATTR. Early diagnosis is even more urgent now given the availability of disease modifying treatments.

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