Primary Carnitine Deficiency – A Rare Treatable Cause of Cardiomyopathy and Massive Hepatomegaly

Deswal, Shivani; Bijarnia‐Mahay, Sunita; Manocha, Vinamr; Hara, Keiichi; Shigematsu, Yosuke; Saxena, Renu; Verma, Ishwar C.

doi:10.1007/s12098-016-2227-7

Cited by 7 publications

(6 citation statements)

References 11 publications

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“…Notably, 5 variants, including potentially the one in SLC22A5 , had not been previously documented in public databases. In a case report, Deswal et al [ 29 ] described a 9-month-old boy suffering from hypertrophic cardiomyopathy, significant hepatomegaly, and jaundice with extremely low free carnitine levels. Genetic analysis identified compound heterozygous mutations in the SLC22A5 gene.…”

Section: Discussionmentioning

confidence: 99%

A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features

Jolfayi,

Naderi,

Ghasemi

et al. 2024

BMC Cardiovasc Disord

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Background Primary carnitine deficiency (PCD) denotes low carnitine levels with an autosomal recessive pattern of inheritance. Cardiomyopathy is the most common cardiac symptom in patients with PCD, and early diagnosis can prevent complications. Next-generation sequencing can identify genetic variants attributable to PCD efficiently. Objective We aimed to detect the genetic cause of the early manifestations of hypertrophic cardiomyopathy and metabolic abnormalities in an Iranian family. Methods We herein describe an 8-year-old boy with symptoms of weakness and lethargy diagnosed with PCD through clinical evaluations, lab tests, echocardiography, and cardiac magnetic resonance imaging. The candidate variant was confirmed through whole-exome sequencing, polymerase chain reaction, and direct Sanger sequencing. The binding efficacy of normal and mutant protein-ligand complexes were evaluated via structural modeling and docking studies. Results Clinical evaluations, echocardiography, and cardiac magnetic resonance imaging findings revealed hypertrophic cardiomyopathy as a clinical presentation of PCD. Whole-exome sequencing identified a new homozygous variant, SLC22A5 (NM_003060.4), c.821G > A: p.Trp274Ter, associated with carnitine transport. Docking analysis highlighted the impact of the variant on carnitine transport, further indicating its potential role in PCD development. Conclusions The c.821G > A: p.Trp274Ter variant in SLC22A5 potentially acted as a pathogenic factor by reducing the binding affinity of organic carnitine transporter type 2 proteins for carnitine. So, the c.821G > A variant may be associated with carnitine deficiency, metabolic abnormalities, and cardiomyopathic characteristics.

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Section: Discussionmentioning

confidence: 99%

A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features

Jolfayi,

Naderi,

Ghasemi

et al. 2024

BMC Cardiovasc Disord

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“…The therapeutic dose of levocarnitine should be adjusted according to alterations in its concentration in the blood of individual patients, as well as the blood alkalinity and the degree of the disease in order to maintain the stability of the tissues and blood. A high dose levocarnitine treatment may cause diarrhea, nausea and other gastrointestinal discomforts; however, the dose can be reduced and once the adverse reactions have improved, it can be gradually increased to the initial treatment dose (20). Patients with PCD require a lifelong treatment with levocarnitine, and a sudden withdrawal may result in a rapid drop in the plasma carnitine concentration, causing recurrent Reye syndrome and even sudden death (21).…”

Section: Discussionmentioning

confidence: 99%

Primary carnitine deficiency in two sisters with intractable epilepsy and reversible metabolic cardiomyopathy: Two case reports

Yang

Liu

2020

Exp Ther Med

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Primary carnitine deficiency (PCD) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. When carnitine cannot be transported into the cells, fatty acid oxidation is impaired, resulting a variety of symptoms, such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The clinical manifestations and outcomes of different cases with PCD vary among patients. The present case report focused on two sisters with PCD. The younger sister presented with intractable epilepsy, and the older sister presented with reversible metabolic cardiomyopathy. Potential mutations in the SLC22A5 gene were investigated within the family, and a nonsense mutation [c.760C>T (p.R254X)] was identified in four family members. The two sisters harbored homozygous mutations, whereas their parents presented heterozygous mutations. Metabolic disease screening revealed low plasma free carnitine levels (<5 µmol/l) in the two sisters. The plasma free carnitine levels of their parents were normal, and they were asymptomatic. PCD in the two patients was managed using oral levocarnitine. The metabolic cardiomyopathy of the older sister improved following 3 months of treatment. However, the epilepsy of the younger sister was recurrent with oral antiepileptic therapy lasting one year and eight months, and epilepsy was finally controlled following right cerebral resection. The present case report demonstrated that the clinical manifestations presented by patients with PCD within the same family were different. The results indicated that treatment with levocarnitine supplementation should be initiated as soon as possible before irreversible organ damage occurs. In addition, metabolic decompensation and cardiac muscle functions were improved following carnitine supplementation. The resection of the severely diseased unilateral brain combined with carnitine supplementation and antiepileptic therapy may be an effective treatment for PCD with intractable epilepsy complications.

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“…Evaluation of free carnitine levels may be appropriate for nutrition management, particularly if there are clinical concerns, such as unexpected hypoglycemia, cardiomyopathy, or chronic PN/dialysis use. Free carnitine <10 μM may reflect chronic deficiency and justify supplementation (25). Currently, there is a lack of clarity on how to monitor and supplement carnitine, which points the way for future research.…”

Section: Evaluation Indicators and Toolsmentioning

confidence: 99%

Research progress on nutritional support in the neonatal and pediatric populations receiving extracorporeal membrane oxygenation

Zhang,

Zhao,

Jia

2024

Front. Nutr.

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Nutritional support is crucial for the prognosis of children supported by extracorporeal membrane oxygenation (ECMO). This article discusses the latest research progress and guideline recommendations for nutritional support during ECMO. We summarize the nutritional status and evaluation of ECMO patients, nutritional support methods and timing, trace elements, the impact of continuous renal replacement therapy (CRRT), and energy requirements and algorithms. The article shows that malnutrition is high in ECMO patients compared to other critically ill patients, with nearly one-third of patients experiencing a decrease in nutritional indicators. The timing of the initiation of nutrition is very important for the nutritional status of the child. Early enteral nutrition can improve patient prognosis, which is the most commonly used, with parenteral nutrition as a supplement. However, the proportion of enteral nutrition is relatively low, and a stepwise nutrition algorithm can determine when to initiate early enteral nutrition and parenteral nutrition. Malnourishment during critical illness have been associated with increased morbidity as well as increased mortality. Nutritional status should be evaluated at admission by screening tools. In addition, changes in the levels of several metabolites in vivo, such as blood lipids, carnitine, and thiamine, can also reflect the degree of nutritional deficiency in critically ill children. This article provides a reference for the implementation of nutrition of pediatric ECMO patients and further research on nutritional support.

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Primary Carnitine Deficiency – A Rare Treatable Cause of Cardiomyopathy and Massive Hepatomegaly

Cited by 7 publications

References 11 publications

A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features

A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features

Primary carnitine deficiency in two sisters with intractable epilepsy and reversible metabolic cardiomyopathy: Two case reports

Research progress on nutritional support in the neonatal and pediatric populations receiving extracorporeal membrane oxygenation

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