Primary Carnitine Deficiency and Cardiomyopathy

Fu, Lei; Huang, Mei‐Rong; Chen, Shubao

doi:10.4070/kcj.2013.43.12.785

Cited by 65 publications

(85 citation statements)

References 47 publications

(57 reference statements)

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“…Primary carnitine deficiency is a fatty acid oxidation disease resulting from defective carnitine transport. Patients usually present with episodes of hypoketotic hypoglycemia, hepatomegaly, muscle weakness and CMP with congestive heart failure . Consistently, our patient with primary carnitine deficiency presented with recurrent pneumonia and hypertrophic CMP.…”

Section: Discussionsupporting

confidence: 83%

Respiratory manifestations in inherited metabolic diseases: 6‐year single‐center experience

İlarslan

Günay

Çobanoğlu

et al. 2019

Pediatric Pulmonology

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Objectives We aimed to call attention to respiratory system manifestations which occur in the course of many inherited metabolic diseases (IMD), and present as the leading cause of death. Materials and Methods We retrospectively reviewed the diagnosis, treatment, and outcome of patients evaluated at our hospital between June 2012 and June 2018 with a diagnosis of IMD and accompanying respiratory manifestations. Results A total of 50 children (29 [58%] male, 21 [42%] female) with IMD and respiratory manifestations were defined. Disorders of intracellular metabolism (n = 33, 66%) formed the majority, followed by intoxication type metabolic disorders (n = 9, 18%) and energy metabolism disorders (n = 8, 16%). The most frequent respiratory symptoms were snoring (20, 40%), tachypnea (16, 32%) and wheezing (14, 28%). Physical examination findings were signs of respiratory distress (n = 28, 56%), crackles (n = 24, 48%), thoracic deformity (n = 23, 46%), decreased breath sounds (n = 17, 34%), rhonchus (n = 17, 34%), wheezing (n = 17, 34%) and stridor (n = 10, 20%). Major respiratory manifestations were chronic airway aspiration (n = 23, 46%), upper airway obstruction (n = 23, 46%), and recurrent pneumonia (n = 18, 36%). Twenty‐three 23 patients (46%) experienced endotracheal intubation, 9 patients (18%) required whole‐house mechanical ventilation and tonsilloadenoidectomy was performed in 7 patients (14%). Overall survival rate was 70% (n = 35) in a median follow‐up period of 2.36 (0.05‐5.86) years. Conclusions Respiratory system manifestations of IMD strongly relate with increased morbidity and mortality. Therefore, prompt diagnosis and correct intervention of respiratory complications with a multidisciplinary team including pediatric metabolic diseases specialists, pulmonologists, otorhinolaryngologists, physiotherapists, and anesthesiologists are crucial to prevent progression and irreversible damage.

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Section: Discussionsupporting

confidence: 83%

Respiratory manifestations in inherited metabolic diseases: 6‐year single‐center experience

İlarslan

Günay

Çobanoğlu

et al. 2019

Pediatric Pulmonology

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“…The rate-limiting step in FAO is the transfer of long chain acyl-CoA fatty acids into the mitochondria by carnitine palmitoyltransferase 1 (CPT1) to form fatty acylcarnitines (Fu et al, 2013). This step is inhibited by malonyl-CoA, which is produced from acetyl-CoA by acetyl-CoA carboxylase (ACC) (Dagher et al, 2001).…”

Section: Fatty Acid B-oxidationmentioning

confidence: 99%

Angiogenesis revisited – role and therapeutic potential of targeting endothelial metabolism

Stapor

Wang

Goveia

et al. 2014

Journal of Cell Science

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Clinically approved therapies that target angiogenesis in tumors and ocular diseases focus on controlling pro-angiogenic growth factors in order to reduce aberrant microvascular growth. Although research on angiogenesis has revealed key mechanisms that regulate tissue vascularization, therapeutic success has been limited owing to insufficient efficacy, refractoriness and tumor resistance. Emerging concepts suggest that, in addition to growth factors, vascular metabolism also regulates angiogenesis and is a viable target for manipulating the microvasculature. Recent studies show that endothelial cells rely on glycolysis for ATP production, and that the key glycolytic regulator 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase 3 (PFKFB3) regulates angiogenesis by controlling the balance of tip versus stalk cells. As endothelial cells acquire a tip cell phenotype, they increase glycolytic production of ATP for sprouting. Furthermore, pharmacological blockade of PFKFB3 causes a transient, partial reduction in glycolysis, and reduces pathological angiogenesis with minimal systemic harm. Although further assessment of endothelial cell metabolism is necessary, these results represent a paradigm shift in anti-angiogenic therapy from targeting angiogenic factors to focusing on vascular metabolism, warranting research on the metabolic pathways that govern angiogenesis.

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“…Characteristic ECG features, similar to our case, have indeed been described in PCD patients and these include high peaked T-waves, shortening or prolongation of the QTc interval and ventricular ectopy alongside evidence for left ventricular hypertrophy. [7][8][9]26,27 Interestingly, mice with induced carnitine deficiency display shortening of the QTc interval and spontaneous sustained ventricular tachycardia, which was not observed in control mice. 28 These data suggest that the mechanism of sudden death from arrhythmia in PCD patients might involve abnormalities of the QTc interval.…”

Section: Discussionmentioning

confidence: 99%

“…6 The clinical presentation varies widely with respect to age of disease onset and organ involvement, where the patient may be asymptomatic or suffer a life-threatening cardiomyopathy. 7 In early infancy, patients typically present with metabolic decompensation with episodes of hypoketotic hypoglycemia and hepatomegaly, elevated transaminases, and hepatic encephalopathy. Later in childhood (around the age of 4 years), the presentation is characterized by muscle weakness, dilated or hypertrophic cardiomyopathy and congestive heart failure.…”

Section: Introductionmentioning

confidence: 99%

Exome sequencing identifies primary carnitine deficiency in a family with cardiomyopathy and sudden death

et al. 2017

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Pediatric cardiomyopathy is a rare but severe disease with high morbidity and mortality. The causes are poorly understood and can only be established in one-third of cases. Recent advances in genetic technologies, specifically next-generation sequencing, now allow for the detection of genetic causes of cardiomyopathy in a systematic and unbiased manner. This is particularly important given the large clinical variability among pediatric cardiomyopathy patients and the large number of genes (>100) implicated in the disorder. We report on the performance of whole-exome sequencing in members of a consanguineous family with a history of pediatric hypertrophic cardiomyopathy and sudden cardiac death, which led to the identification of a homozygous stop variant in the SLC22A5 gene, implicated in primary carnitine deficiency, as the likely genetic cause. Targeted carnitine tandem mass spectrometry analysis in the patient revealed complete absence of plasma-free carnitine and only trace levels of total carnitine, further supporting the causality of the SLC22A5 variant. l-carnitine supplementation in the proband led to a rapid and marked clinical improvement. This case illustrates the use of exome sequencing as a systematic and unbiased diagnostic tool in pediatric cardiomyopathy, providing an efficient route to the identification of the underlying cause, which lead to appropriate treatment and prevention of premature death.

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Primary Carnitine Deficiency and Cardiomyopathy

Cited by 65 publications

References 47 publications

Respiratory manifestations in inherited metabolic diseases: 6‐year single‐center experience

Respiratory manifestations in inherited metabolic diseases: 6‐year single‐center experience

Angiogenesis revisited – role and therapeutic potential of targeting endothelial metabolism

Exome sequencing identifies primary carnitine deficiency in a family with cardiomyopathy and sudden death

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