Recurrent Postinfectious Rhabdomyolysis in a 5-Year-Old Girl

Introduction

Rhabdomyolysis is common in pediatric clinical practice. The majority of patients with rhabdomyolysis are admitted to hospitals with complaints of myalgia, muscle tenderness and dark urine. Rhabdomyolysis in childhood may be due to trauma, infections, fever, inherited muscle diseases, excessive exercises and long surgical procedures. However, when rhabdomyolysis recurs and creatine kinase levels higher than expected, it is necessary to evaluate the possibility of underlying metabolic disorders even in the presence of other triggering factors. Fatty acid oxidation defects, glycogen storage disease and mitochondrial myopathies are the three main groups of metabolic myopathies (Nance JR et al.; Muscle & Nerve 2015; 793–810)

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of long-chain fatty acid (LCFA) oxidation. Three clinical presentations are a mild adult-onset myopathic form, a severe infantile form, and a lethal neonatal form. The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and is the most frequent cause of hereditary myoglobinuria (Wieser T,GeneReviews^® [Internet]; 2019). Since the first description of the myopathic form by DiMauro & DiMauro in 1973 (DiMauro S et al., Science 1973; 929–931), around 400 unrelated families with different three forms of CPT II deficiency have been published (Wieser T,GeneReviews^® [Internet]; 2019, Joshi PR et al., Molecules;2020;1784). Symptoms of the myopathic form may be mild and physical impairment may not occur (Wieser T,GeneReviews^® [Internet]; 2019, Joshi PR et al., Molecules 2020;1784) ; therefore, it can be predicted that there should be a lot more undiagnosed cases of CPT II deficiency.

Herein, we report on a 5-year-old girl with acute postinfectious rhabdomyolysis, who was diagnosed with a myopathic form of carnitine palmitoyltransferase II (CPT II) deficiency.

Case Description

A 5-year-old girl was admitted to our hospital with a 2-day history of fever, sore throat, weakness, muscle pain. A year ago, she was hospitalized for rhabdomyolysis triggered by an infection that was managed by intravenous fluids at a local hospital without complications. Other than that episode, she had no history of myalgia or muscle weakness during rest or with physical activity. She has normal growth and normal age-appropriate motor development. Her parents were consanguineous and family history did not give a clue for renal, muscular or other chronic systemic diseases.

On physical examination enlarged cryptic tonsils were found. Her body temperature was 37.7 °C, blood pressure 100/70 mmHg and heart rate 105 beats/min. Neurological examination disclosed muscle tenderness of the lower limbs and muscle strength (Medical Research Council) was 4/5 in upper limbs and 3/5 in lower limbs, bilaterally. Laboratory findings were as follows: hemoglobin: 9.8 g/dL, platelet count: 259×103/mm³, serum aspartate aminotransferase: 4466 U/L (<48 U/L), alanine aminotransferase: 1415 U/L (0–39 U/L), creatine kinase (CK): 91900 U/L (34–204 U/L), CK-MB: 1975 U/L (<25 U/L), lactate dehydrogenase: 4203 U/L (142–297 U/L). Serum electrolytes and renal function tests were within normal limits. Urine analysis with a dipstick revealed a 3+ blood reaction, but no erythrocytes were found on microscopic examination. C-reactive protein was mildly elevated at 19.6 mg/L. Influenza A H3N2 was positive in the respiratory viral panel. Oseltamivir was started. She was transferred to the pediatric intensive care unit and managed with high glucose infusion, intravenous hydration and urine alkalization. CK rapidly decreased daily over 1 week ([Fig. 1]), in line with liver function tests. Myalgia and the muscle strength of the patient gradually improved.

Fig. 1 Creatine kinase trend during hospitalization

History of a previous episode of rhabdomyolysis led to further laboratory studies. Laboratory values obtained including fasting glucose, venous blood gas, ammonia, lactate, and pyruvate were all within normal limits. Ultrasonography examination of the kidneys showed normal kidney size and echogenic structure. Echocardiography was normal. Metabolic workup, including plasma and urine amino acid analysis, urinary organic acid profile by gas chromatography and mass spectrometry and dried blood spot carnitine and acylcarnitine profile by tandem mass spectrometry was normal. Recurrent episodes of rhabdomyolysis in childhood triggered by infections with normal acylcarnitine profile was suspicious of lipin-1 deficiency and CPT II deficiency, caused by mutations in LPIN1 and CPT2 genes, respectively. LPIN1 gene sequencing was normal. A next-generation sequencing panel encompassing genes responsible for disorders of lipid metabolism revealed a homozygous c.338C>T (p.Ser113Leu) variant in CPT2 gene (reference sequence NM_000098.3) ([Fig. 2]), which is reported to be the most common mutation reported in individuals with the myopathic form of CPT II deficiency (Wieser T et al., Neurology 2003; 1351–1353).

Fig. 2 Genetic analysis of the patient shows homozygous c.338C>T (p.Ser113Leu) variant in CPT2 gene

The patient was started a diet rich in carbohydrates with a restriction of long-chain fatty acids. She was advised to avoid excessive physical exertion and exposure to cold and to receive additional carbohydrates before exercise and during any acute illness. She was discharged on the 10^th day of hospitalization without any complications.

Publication History

Article published online:
09 October 2020