Variants in HNRNPDL and SETX Not Necessarily Indicate Familial Amyotrophic Lateral Sclerosis or Limb Girdle Muscular...

Genetic work-up is useful for the identification of a primary myopathy. However, even sophisticated genetic methods may fail to detect the underlying cause of myopathy as in the following case. The patient is a 52-year-old female with a history of epilepsy, arterial hypertension, atrial flutter requiring cardioversion, ablation, and anticoagulation, coronary heart disease, hyperlipidemia, and hyper-CKemia. At age 52 years, she was referred for heart failure due to ischemic cardiomyopathy requiring appropriate medication and implantation of an ICD. During hospitalization she developed acute muscular respiratory failure requiring mechanical ventilation. Genetic panels for myopathy, neuropathy, and cardiomyopathy revealed variants of unknown significance in the HNRNPDL and SETX genes respectively. Clinical presentation and muscle biopsy, however, suggested metabolic myopathy. Acute muscular respiratory failure may require traditional diagnostic work-up for primary myopathy and long-term invasive and non-invasive ventilation. Panel investigations not necessarily lead to a conclusive diagnosis. The multisystem nature of the condition rather suggests a metabolic defect than LGMD-1G or fALS as genetic findings suggested.