Unmasking of Carnitine Palmitoyltransferase Deficiency during an Acute Exacerbation of Asthma Complicated by Rhabdomyolysis in a Soldier

Military Medicine, Oct 2004 by Gilad, Jacob, Pirogovsky, Avinoam, Bartal, Carmi

Rhabdomyolysis is a life-threatening condition that may result from various etiologies. We report a rare case of severe rhabdomyosis in a soldier after a mild acute asthma exacerbation. Further work-up revealed an underlying deficiency of type II carnitine palmitoyltransferase. The case is discussed along with a review of the literature. It is concluded that acute asthma exacerbations may be a unique precipitating factor of rhabdomyolysis and may therefore unmask underlying metabolic myopathies. Asthma may cause rhabdomyolysis through several different mechanisms, and thus the occurrence of rhabdomyolysis in the context of asthma exacerbations should warrant a work-up for metabolic diseases, especially in the presence of high creatine kinase levels. Given the high incidence of asthma, especially among young adults, a high index of suspicion is needed in order that rhabdomyolysis be promptly diagnosed and treated.

Introduction

Rhabdomyolysis is a life-threatening condition that may result from various etiologies, the most important of which are congenital or acquired metabolic disorders, trauma, infection, exertion, and drug adverse events. ' Rarely, rhabdomyolysis may complicate the course of an acute exacerbation of asthma by either of several pathophysiologic mechanisms.

We report a case of severe rhabdomyosis in a soldier who presented with an acute asthma exacerbation. Laboratory analysis revealed a deficiency of carnitine palmitoyl-transferase (CPT) type II. The case is discussed along with a review of the literature regarding the association of asthma and rhabdomyolysis in the context of congenital metabolic myopathies.

Case Report

The patient was an 18-year-old soldier in basic training. Past history included bronchodilator-responsive mild intermittent asthma that did not require regular drug therapy. A lung function test was reportedly normal 1 year before recruitment. No past difficulty in performing physical exercise, including muscular aches or cramps, was reported.

Six weeks after the beginning of training, the patient complained of dyspnea that began during routine exercise, which included walking a distance of 3 miles, and did not resolve after β2 agonist inhalation. The patient participated fully in all endurance training over the previous 6 weeks. There was no recent history of an intercurrent febrile illness, dehydration, stress reaction, fasting, or exposure to extreme cold. Physical examination was unremarkable, and ßl agonist therapy was continued.

On the following day, the dyspnea recurred and the patient complained of severe and diffuse muscle aches. No strenuous physical activity was performed that day. On examination, there were no signs of respiratory distress or dehydration. His pulse was 92 beats per minute, his oxygen saturation was 98%, and his blood pressure and temperature were normal. Bilateral wheezes where noted on auscultation. Inhaled β2 agonists and budesonide were administered at standard dosages.

Inhalation therapy resulted in clinical improvement of dyspnea and wheezing, but the patient still complained of muscle aches and also of muscle fasciculations. Vital signs were normal. A urine sample disclosed dark brown urine, and the dipstick was positive for blood. An intravenous infusion of lactated Ringer's solution was started, and the patient was transferred to the emergency room because of suspected rhabdomyolysis.

On hospital admission, his pulse was 83 beats per minute, his respiratory rate was 18 per minute, his blood pressure was 134/75 mm Hg, he had a rectal temperature of 36.9°C, and his oxygen saturation was 99% while breathing room air. Laboratory studies revealed the following: hemoglobin, 14.5 g/dL; leukocyte count, 10,800/mm^sup 3^; platelets, 264,000/mm^sup 3^; glucose, 96 mg/dL; creatinine, 1.8 mg/dL; urea, 61 mg/dL; sodium, 137 mEq/L; potassium, 5.2 mEq/L; chloride, 102 mEq/L; calcium, 9.0 mg/dL; phosphate, 5.8 mg/dL; and magnesium, 2.7 mEq/L. Serum creatine kinase (CK) was 159,920 IU/L (muscle-brain isoenzyme fraction

Hydration and alkalinization were achieved by continuous infusion of intravenous saline and bicarbonate. Over the following days, serum creatinine levels peaked at 5.1 mg/dL. Marked improvement was noted after therapy, and the patient was discharged with a residual renal dysfunction (creatinine, 1.7 mg/dL).

A postdischarge work-up for possible etiologies of rhabdomyolysis revealed a type II CPT deficiency with residual enzyme activity of 13% compared with normal controls by means of the isotope exchange test of the patient's lymphocytes.

Discussion

We report a case of rhabdomyolysis in a patient with lateonset type II CPT deficiency, the most common inherited disorder of lipid metabolism affecting skeletal muscle. There are two distinct forms of type II CPT deficiency-the rare, severe, and fatal infantile form and the benign, muscular, adult-onset form.2

The hallmark of adult-onset CPT deficiency myopathy is myoglobinuria. The classic manifestation includes recurrent myoglobinuria and rhabdomyolysis, which are typically precipitated by various factors including stress, fasting, cold exposure, strenuous exercise, and acute infections such as influenza.3 Uncommonly, this condition may manifest as chronic myopathy with limb pain and stiffness without myoglobinuria. The phenotypic heterogeneity in CPT type II deficiency is related to the type and extent of enzymatic defect as well as to precipitating factors.3 That rhabdomyolysis occurred during the course of an acute asthma exacerbation in this case is intriguing and deserves further discussion.