Cause of recurrent rhabdomyolysis, carnitine palmitoyltransferase II deficiency and novel pathogenic mutation

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal inherited metabolic disorder in which the β-oxidation of the long chain fatty acids is defective. The clinical presentation may be in various forms; it presents itself in the severe form during neonatal and infantile periods and as the less severe myopathic form in the school age and adolescence. While the severity of the rhabdomyolysis attacks varies, occasionally the clinical course may be complicated with acute renal failure. Acylcarnitine analysis may help in the diagnosis of CPT II, but its normality does not indicate the absence of the disease. If there is strong suspicion, genetic analysis should be performed on the cases. In this article, we present a 15-year-old male patient who had two rhabdomyolysis attacks triggered by infection and starvation. Acylcarnitine analysis of the case was normal, CPT II deficiency was considered when the history was evaluated, and CPT II gene c.137A>G (p.Gln46Arg) homozygous novel pathogenic mutation was detected. CPT II deficiency is one of the most common causes of metabolic rhabdomyolysis in patients with recurrent episodes of rhabdomyolysis.

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An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0324 ◽

2017 ◽

Vol 30 (2) ◽

Author(s):

Engin Melek ◽

Fatma Derya Bulut ◽

Bahriye Atmış ◽

Berna Şeker Yılmaz ◽

Aysun Karabay Bayazıt ◽

...

Keyword(s):

Clinical Phenotype ◽

Carnitine Palmitoyltransferase ◽

Long Chain Fatty Acids ◽

Infantile Form ◽

Dark Urine ◽

Recurrent Rhabdomyolysis ◽

History Of ◽

Carnitine Palmitoyltransferase Ii ◽

Cpt Ii Deficiency ◽

Long Chain

AbstractCarnitine palmitoyltransferase II (CPT-II) deficiency is an autosomal recessively inherited disorder involving the β-oxidation of long-chain fatty acids, which leads to rhabdomyolysis and subsequent acute renal failure. The clinical phenotype varies from a severe infantile form to a milder muscle form. Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise. As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. After excluding the other causes of rhabdomyolysis, with the help of metabolic investigations, the patient was suspected to have CPT-II deficiency, the most common cause of metabolic rhabdomyolysis. Our aim in presenting this case is to emphasize considering rhabdomyolysis in the differential diagnosis of dark urine in order to prevent recurrent rhabdomyolysis and renal injury.

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Carnitine Palmitoyltransferase II deficiency, a Rare Cause of Rhabdomyolysis: A Case Report

Case Reports in Clinical Practice ◽

10.18502/crcp.v4i3.1715 ◽

2019 ◽

Author(s):

Parisa Farshchi ◽

Sahar Karimpour Reyhan ◽

Mahsa Abbaszadeh ◽

Shadi Shiva

Keyword(s):

Acute Kidney Injury ◽

Muscle Weakness ◽

Muscle Biopsy ◽

Kidney Injury ◽

Carnitine Palmitoyltransferase ◽

Metabolic Myopathy ◽

Dark Urine ◽

Recurrent Rhabdomyolysis ◽

Carnitine Palmitoyltransferase Ii ◽

Cpt Ii Deficiency

Introduction: Muscle weakness and rhabdomyolysis have a wide range of differential diagnosis. In many situations, they are induced by seizure, trauma, drugs, and toxins. They could also be due to inflammatory or metabolic myopathies. Identifying the exact cause is crucial and sometimes challenging. Case Presentation: A 23-year-old man was admitted to our hospital with muscle weakness, fatigue, dyspnea, and dark urine, all preceded by flu-like symptoms, myalgia, and fever. Due to reduced muscle strength, dark urine, elevated serum creatine kinase, and serum creatinine, he was diagnosed with rhabdomyolysis and acute kidney injury. Muscle biopsy was performed three years before for the patient, due to a history of similar episodes and exercise intolerance. Because of recurrent episodes of muscle weakness and rhabdomyolysis along with the negative muscle biopsy for inflammatory myopathies, we suspected metabolic myopathy as a cause. Therefore, metabolic screening was performed for the patient, and he was diagnosed with metabolic myopathy known as Carnitine Palmitoyltransferase II (CPT II) deficiency. Conclusion: In patients with recurrent rhabdomyolysis, we should consider inherited myopathies, especially carnitine palmitoyltransferase II deficiency and glycogen storage disease type V (McArdle disease) as likely causes. CPT II deficiency is regarded as a preventable cause of recurrent rhabdomyolysis. Therefore, by early diagnosis of this disorder we could prevent recurrent episodes of rhabdomyolysis and ultimately avoid life-threatening complications like acute kidney injury

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Carnitine Palmitoyltransferase-II Deficiency: Case Presentation and Review of the Literature

Romanian Journal of Internal Medicine ◽

10.2478/rjim-2021-0021 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Benjamin J. Mccormick ◽

Razvan M. Chirila

Keyword(s):

Clinical Manifestations ◽

Treatment Strategies ◽

Autosomal Recessive Disorder ◽

Signs And Symptoms ◽

Carnitine Palmitoyltransferase ◽

Electrolyte Disturbances ◽

Preventative Measures ◽

Recurrent Rhabdomyolysis ◽

Carnitine Palmitoyltransferase Ii ◽

Cpt Ii Deficiency

Abstract Carnitine palmitoyltransferase-II deficiency, an autosomal recessive disorder, is the most common cause of recurrent rhabdomyolysis in adults. Recognition and avoidance of triggers, such as heavy exercise and stress, is key in prevention of further episodes; however, even with preventative measures, many patients will continue to experience periodic symptoms, including rhabdomyolysis. Avoidance of renal failure, correction of electrolyte disturbances and halting further muscle breakdown are the goals of treatment. It is essential for clinicians to recognize the signs and symptoms of acute disease in CPT-II deficiency. We present a case of recurrent rhabdomyolysis requiring hospitalization in a patient with CPT-II deficiency and review the literature for common clinical manifestations, diagnostics, and treatment strategies.

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A newborn case with carnitine palmitoyltransferase II deficiency initially judged as unaffected by acylcarnitine analysis soon after birth

Molecular Genetics and Metabolism Reports ◽

10.1016/j.ymgmr.2017.04.008 ◽

2017 ◽

Vol 11 ◽

pp. 59-61 ◽

Cited By ~ 6

Author(s):

Kenji Yamada ◽

Ryosuke Bo ◽

Hironori Kobayashi ◽

Yuki Hasegawa ◽

Mako Ago ◽

...

Keyword(s):

Carnitine Palmitoyltransferase ◽

Acylcarnitine Analysis ◽

Carnitine Palmitoyltransferase Ii

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Recurrent Myalgia since Early Infancy—Misleading Clinical Course in a Child with Carnitine Palmitoyltransferase-II Deficiency

Neuropediatrics ◽

10.1055/s-0039-1694977 ◽

2019 ◽

Vol 51 (01) ◽

pp. 053-056

Author(s):

Maria Arélin ◽

Stephan Zierz ◽

Uta Ceglarek ◽

Mitja Heinemann ◽

Skadi Beblo ◽

...

Keyword(s):

Fatty Acid ◽

Carnitine Palmitoyltransferase ◽

Early Infancy ◽

Hereditary Diseases ◽

Missense Mutations ◽

Metabolic Myopathies ◽

Muscle Energy ◽

Carnitine Palmitoyltransferase Ii ◽

Cpt Ii Deficiency ◽

Generation Sequencing

AbstractMetabolic myopathies are heterogeneous hereditary diseases affecting skeletal muscle energy supply. Symptoms usually comprise pain, cramps, hypotonia, weakness, and myoglobinuria.We present a boy with recurrent myalgia and weakness after some minutes of exercise or during febrile infections since early infancy. First laboratory workup at the age of 9 years showed no abnormalities, apart from a slightly elevated creatine kinase. After exclusion of common structural and metabolic myopathies, next generation sequencing panel (4 years after the initial diagnostic metabolic workup) revealed two potentially pathogenic missense mutations in the CPT2 gene (c.149C > A (p.P50H) and c.1459G > A (p.E487K)).Our case underscores the clinical variability of muscle carnitine palmitoyltransferase II (CPT II) deficiency and illustrates a pitfall of diagnostic algorithms for metabolic myopathies. Myalgia following exercise of a few minutes duration would have argued for a carbohydrate and against a fatty acid metabolic defect. However, CPT II deficiency is the most common disorder of muscle fatty acid metabolism and should be considered even in atypical scenarios. Analyses of plasma acyl carnitine profile during acute metabolic crises may help to unmask biochemical markers which are often overlooked in dried-blood analyses.

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Normal FGF-21-Serum Levels in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency

International Journal of Molecular Sciences ◽

10.3390/ijms20061400 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1400 ◽

Cited By ~ 3

Author(s):

Leila Motlagh Scholle ◽

Diana Lehmann ◽

Pushpa Joshi ◽

Stephan Zierz

Keyword(s):

Citrate Synthase ◽

Serum Levels ◽

Carnitine Palmitoyltransferase ◽

Fibroblast Growth Factor 21 ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Mitochondrial Fatty Acid ◽

Significant Difference ◽

Carnitine Palmitoyltransferase Ii ◽

Cpt Ii Deficiency

Fibroblast growth factor 21 (FGF-21) is known to be a biomarker for mitochondrial disorders. An upregulation of FGF-21 in serum and muscle of carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II) knock-out mice has been reported. In human CPT II deficiency, enzyme activity and protein content are normal, but the enzyme is abnormally regulated by malonyl-CoA and is abnormally thermolabile. Citrate synthase (CS) activity is increased in patients with CPT II deficiency. This may indicate a compensatory response to an impaired function of CPT II. In this study, FGF-21 serum levels in patients with CPT II deficiency during attack free intervals and in healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The data showed no significant difference between FGF-21 concentration in the serum of patients with CPT II deficiency and that in the healthy controls. The results of the present work support the hypothesis that in muscle CPT II deficiency, in contrast to the mouse knockout model, mitochondrial fatty acid utilization is not persistently reduced. Thus, FGF-21 does not seem to be a useful biomarker in the diagnosis of CPT II deficiency.

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