A previously healthy 36-year-old male was admitted to the medical intensive care unit following a cardiac arrest. On the day of admission to the hospital, he was getting ready for work, but felt quite fatigued and short of breath. He was talking with his wife, and she noted that he looked “blue” and then fell to the floor. He did not have a pulse, and she started emergency medical services (CPR) and contacted emergency medical services (EMS). On arrival, he did not have a pulse and received one dose of epinephrine and was intubated in the field with return of spontaneous circulation. On arrival to the ED, he was hemodynamically stable with normal vital signs, localizing with his arms and opening his eyes to noxious stimulation. He remained intubated and his mental status recovered, but he was unsuccessfully extubated because of hypercarbic respiratory failure over the course of several hours. A full cardiac and pulmonary workup was completed without underlying etiology for his respiratory failure. The neurology serviced was consulted for evaluation of failure to wean. Further history noted progressive dyspnea and fatigue over the last 6 months, but he attributed this to his stress at work. Also, he noted more difficulty with lifting his young children. His neurologic examination was pertinent for mild symmetric deltoid weakness and moderate symmetric hip flexion weakness. The remainder of the neurologic examination was normal. Electrodiagnostic tests were completed with normal nerve conduction studies, but abnormal electromyography with positive sharp waves and fibrillation potentials demonstrated in the deltoid, supraspinatus, iliopsoas, and thoracic paraspinal musculature. The paraspinal musculature also demonstrated complex repetitive discharges and myotonic discharges.
What is the MOST likely underlying cause of the patient’s presentation?
A. Acid maltase deficiencyCorrect Answer: A
The neurologic etiologies of failure to wean from the ventilator are quite broad and can be divided into central (bihemispheric, bithalamic, brain stem, and cervical cord), peripheral nerve, neuromuscular junction, and muscle. The pattern of weakness can help determine the underlying etiology, and electrodiagnostic tests can further determine the underlying cause. In this case, examination demonstrates myopathic pattern of weakness and this is confirmed with the electrodiagnostic testing. The patient has a limb-girdle pattern of weakness with the striking finding of abnormal electromyography within the paraspinal muscles. The clinical history and EMG findings are most consistent with late onset Pompe disease, which is a deficiency in acid maltase. Although muscle biopsy can confirm the diagnosis, there are now blood tests: leukocyte isolates from whole blood for GAA activity and blood spot assay for acid alphaglucosidase activity. Making this diagnosis is crucial as there is enzyme replacement therapy which can improve survival. C9orf72 genetic mutation is associated with ALS-FTD spectrum disorders. Glucose-6-phosphatase deficiency is associated with von Gierke disease, which presents in infancy with hepatosplenomegaly, hypoglycemia during fasting, epilepsy, and lactic acidosis. Laminin A/C is associated with limb-girdle muscle dystrophy, which can present similar but will not have the respiratory and paraspinal muscle findings as Pompe. Zinc finger 9 is associated with myotonic dystrophy type 2 that has a very characteristic “hatchet face” appearance and myotonia on examination.
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