Klin Padiatr 2020; 232(01): 35-36
DOI: 10.1055/a-1061-7384
Short Communication
© Georg Thieme Verlag KG Stuttgart · New York

Fasting-Induced Rhabdomyolysis in An Adolescent Girl

Fasteninduzierte Rhabdomyolyse bei einem jugendlichen Mädchen
Husniye Yucel
1  Department of Pediatrics, Dr. Sami Ulus Maternity and Children’s Health and Diseases Training and Research Hospital, Ankara, Turkey
Emine Polat
1  Department of Pediatrics, Dr. Sami Ulus Maternity and Children’s Health and Diseases Training and Research Hospital, Ankara, Turkey
Meltem Akcaboy
1  Department of Pediatrics, Dr. Sami Ulus Maternity and Children’s Health and Diseases Training and Research Hospital, Ankara, Turkey
Saliha Senel
1  Department of Pediatrics, Dr. Sami Ulus Maternity and Children’s Health and Diseases Training and Research Hospital, Ankara, Turkey
Cigdem Seher Kasapkara
2  Department of Pediatric Metabolism, Dr. Sami Ulus Gynecology Obstetrics and Child Health and Diseases Training and Research Hospital, Ankara, Turkey
› Author Affiliations
Further Information

Publication History

Publication Date:
17 December 2019 (online)

A 16-year-old girl was admitted to our hospital because of fatigue and breathing difficulty for the previous 2 days. She had been complaining of shortness of breath and dyspnea intermittently for about 1 year. She gave the history of getting tired when she remained standing up and moving for a long time. Chest pain and breathing difficulty were accompanied intermittently to this tiredness. She could not attend to any physical education classes in the school for this reason. She gave the history of fasting for a day for the first time the day before, and her fatigue and exhaustion became even greater. She did not have fever or infection previous 10 days. The prenatal history was unremarkable. She was born at full-term gestation after an uncomplicated pregnancy with a birth weight of 2800 gr from a consanguineous family (first degree cousins). She was born in Turkey. In Turkey extended newborn-screening is not being performed including MS/MS and acylcarnitine profiling. She had no congenital abnormalities and her family history was unremarkable. The physical examination revealed normal physical development and neuromuscular examination was intact. Laboratory examinations including acute phase reactants, serum electrolytes, serum glucose, and albumin levels, serum lactate levels and also renal function tests were normal. Liver function tests showed abnormality with aspartate aminotransferase: 1936 U/L (normal range: 10–40 U/L), alanine aminotransferase: 314 U/L (normal range: 10–40 U/L) lactate dehydrogenase 3292 IU/L (normal range: 98–192 IU/L). Urine analysis revealed myoglobinuria. Serum creatine kinase was 137.590 IU/L and rhabdomyolysis was diagnosed. Viral markers and serologic evaluation for infections were negative. There was no history of crush or trauma. She was not receiving any concomitant medications. Clinical cardiac evaluation, the electrocardiogram, and echocardiography were normal. Acute rhabdomyolysis was treated with hydration and alkalization of the urine to protect renal function and to prevent acute renal failure secondary to myoglobinuria. Metabolic screening was performed and the diagnosis was based on an abnormal acylcarnitine and urine organic acid profile. Acylcarnitine analysis by tandem mass spectrometry (MS/MS) revealed elevation of serum tetradecenoylcarnitine (C14:1): 0.88 µmol/L (0–0.33 µmol/L); C14: 0.39 µmol/L (0–0.36 µmol/L ); C14:2: 0.50 µmol/L (0–0.41 µmol/L); C18: 0.64 µmol/L (0–0.61 µmol/L); free carnitine level: 20 µmol/L (10–60 µmol/L) which represents an abnormal acylcarnitine profile associated with the mitochondrial β-oxidation defect suggesting very long chain acyl-CoA dehydrogenase deficiency (VLCADD). The urine organic acid profile revealed dicarboxylic aciduria. The diagnosis was confirmed genetically. Direct sequencing of the acyl-CoA dehydrogenase, very long-chain gene (ACADVL), that codes VLCADD, revealed a novel homozygous variant c.1723C>T (p.Leu575Phe) for myopathic-type VLCAD deficiency. The molecular genetic analysis revealed heterozygousity for a novel c.1723C>T (p.Leu575Phe) variant in her parents. Soon after diagnosis, we instructed to reduce fat intake, avoid fasting and medications known to cause rhabdomyolysis. Middle chain fatty acid consumption was also recommended. After the introduction of dietary treatment, no further metabolic crises necessitating hospital admission has occurred, neither have fixed myopathic changes developed.

We reported the case of a 16-year-old female patient who presented with rhabdomyolysis, muscle weakness, myalgia after one day of fasting to remind that metabolic myopathies should be diagnosed regardless of age. The clinical conditions that metabolic myopathies should be suspected are recurrent rhabdomyolysis in association with fasting or a viral illness; a history of exercise intolerance, recurrent cramps, and fatigue beginning in childhood; a family history of rhabdomyolysis or exercise intolerance; and severe rhabdomyolysis in children with consanguineous family history.

Rhabdomyolysis is a syndrome typically characterized by muscle necrosis and the release of intracellular constituents of muscle into the circulation. Creatine kinase levels are typically markedly elevated, and muscle pain and myoglobinuria may be present. Differential diagnosis in children usually consists of infections, trauma, heavy exercise, toxins, genetic and inflammatory myopahties and metabolic diseases [4],[7].

Metabolic myopathies should be suspected when recurrent episodes of rhabdomyolysis after exertion or in association with fasting or a viral illness are present. The last two associations occur most commonly with carnitine palmitoyl transferase II deficiency and the other disorders of lipid metabolism [7],[1]. Recognized heritable causes of rhabdomyolysis are defects in the glycogen metabolism and glycolysis, in the respiratory chain or in fatty acid oxidation [5],[8]. Within the group of disorders of fatty acid metabolism, carnitine palmitoyl-transferase II deficiency is the most frequently reported condition, but other defects, like VLCAD deficiency, should also been considered [14],[6]. Also Lipin-1 deficiency causes potentially fatal severe, recurrent episodes of rhabdomyolysis triggered by infection. [8]

Very long chain acyl-CoA dehydrogenase deficiency (VLCADD) is a lipid metabolism disorder that was first described in 1993. It is an autosomal recessive genetic disorder in which the first step in the mitochondrial β-oxidation spiral of fatty acids for 14–20 carbons is defective [4]. ACADVL is located on chromosome 17p13.1 and has 20 exons [12],[6].The phenotype is heterogeneous ranging from the severe neonatal form presenting with hypo-ketotic hypoglycemia, liver dysfunction and rapidly fatal cardiomyopathy over the infantile form with episodes of hypo-ketotic hypoglycemia and liver dysfunction to the adult myopathic form. The myopathic phenotypes are characterized by episodic muscle weakness and rhabdomyolysis triggered by fasting and strenuous exercise [3],[16]. Here we report a 16 year-old patient with a novel mutation in the ACADVL gene presenting as adult myopathic form VLCADD.

Early diagnosis and treatment of VLCADD is essential to prevent cardiomyopathy, arrhythmia, hypoketotic hypoglycemia, rhabdomyolysis and death [14]. Neonatal screening programs for VLCADD have been implemented recently in various countries. Mildly elevated C14:1 carnitine on third day of newborn strongly suggests VLCADD. Patients with VLCADD detected thorough newborn screening are usually asymptomatic during the well state but they are at risk for metabolic decompensation during catabolic episodes such as intercurrent infections or other episodes of fasting [9] [6]. Genetic confirmation and enzymatic analysis is helpful in designing the appropriate follow-up and therapeutic regime for these patients. The mainstay of therapy is the prevention of recurrent attacks by an anti-catabolic therapy during surgery, prolonged fasting, perioperative stress to minimize fasting stress. Recently, an article proposed an individualized dietary therapy based on the long chain fatty acid oxidation (LC-FAO) flux score in cultured skin fibroblasts of VLCADD patients [2],[11]. Triheptanoin, a seven-carbon fatty acid triglyceride is reported to be a promising drug for patients having persistent myopathy or cardiomyopathy despite the treatment with conventional modalities [13],[14]. Bezafibrate which is a peroxisome proliferator activated receptor agonist that decreases human serum lipid levels has been recently reported to be a promoting drug for fatty acid oxidation disorders based on enhanced transcription β-oxidation enzymes. Clinical trials have reported improvements in some quality of life components [10].

We would like to point out that in the differential diagnosis of recurrent rhabdomyolysis and intermittent fatigue, inherited metabolic disorders should be considered regardless of the patient's age.