Abstract RyR-1 related myopathy is a congenital muscle disorder caused by pathogenic variants in the RYR1 gene, calcium release channel involved in excitation-contraction coupling. It causes mild, non-progressive muscle weakness to severe, early-onset hypotonia, respiratory insufficiency, and perinatal lethality. ALS is a progressive, fatal neurodegenerative disease that causes motor neuron loss, muscle atrophy, and paralysis. Case studies in RYR1 myopathy show respiratory involvement in approximately 22% of children, with 12% requiring ventilatory support, and similar patterns are observed in adults. Diaphragmatic weakness and reduced mobility correlate with lower inspiratory capacity and an increased risk of hypoventilation and type II respiratory failure.Case Presentation A 72-year-old man with CAD s/p CABG and a family history of muscular dystrophy presented with six months of progressive muscle weakness. He first noticed muscle tightness around age 20 and developed progressive dyspnea at 60. Over the past six months, symptoms worsened, with gait difficulty and respiratory decline. Physical examination revealed muscle wasting in the pectoral and biceps regions, impaired balance, and inability to stand on his toes. He reported urinary incontinence, along with episodes of abrupt sleep with transient airway obstruction and cyanosis. Examination revealed mild right-sided ptosis with facial and neck weakness, distal weakness with ankle areflexia, decreased ankle proprioception, and a wide-based ataxic gait. Labs for the autoimmune panel were negative. SPEP and kappa/lambda ratio were unremarkable. CSF showed elevated protein, WBCs, and RBCs, with normal glucose. Chest imaging was negative for acute cardiopulmonary processes. EMG showed severe axonal sensorimotor polyradiculoneuropathy. Neurofilament testing showed 109 pg/mL. CK was elevated at 624 U/L. Genetic studies were positive for the RYR1 gene mutation. The patient was prescribed a noninvasive ventilator for respiratory failure prevention and advised to undergo MIP and MEP monitoring every three months. Discussion This case highlights the importance of various respiratory parameters, including forced vital capacity, sniff nasal inspiratory pressure (SNIP), maximal inspiratory pressure, and maximal expiratory pressure in ALS and RYR-1 related myopathies. Conventionally, FVC and SNIP have been used to guide the timing of non-invasive ventilation and to predict mortality. However, recent studies have shown that MIP and MEP are more sensitive indicators in neuromuscular disorders, as their decline in ALS often occurs before symptom onset and FVC decline, allowing for earlier NIV initiation and improved respiratory outcomes. This case underscores the importance of regular monitoring of MIP and MEP through serial PFTs for improved respiratory outcomes in ALS and RYR1 myopathies. This abstract is funded by: None
Singh et al. (Fri,) studied this question.