3-Methylcrotonyl-CoA carboxylase deficiency in an infant with cardiomyopathy, in her brother with developmental delay and in their asymptomatic father (original) (raw)
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Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake
Annals of Neurology, 1991
A defect in intracellular uptake of carnitine has been identified in patients with severe carnitine deficiency. To define the clinical manifestations of this disorder, the presenting features of 15 affected infants and children were examined. Progressive cardiomyopathy, with or without chronic muscle weakness, was the most common presentation (median age of onset, 3 years). Other patients presented with episodes of fasting hypoglycemia during the first 2 years of life before cardiomyopathy had become apparent. A defect in carnitine uptake was demonstrable in fibroblasts and leukocytes from patients. The defect also appears to be expressed in muscle and kidney. Concentrations of plasma carnitine and rates of carnitine uptake in parents were intermediate between affected patients and normal control subjects, consistent with recessive inheritance. Early recognition and treatment with high doses of oral carnitine may be life-saving in this disorder of fatty acid oxidation.
JIMD Reports, 2011
Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder caused by defective cellular carnitine transport. Patients usually present with predominant metabolic or cardiac manifestations. SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5) gene. Mutation analysis of SLC22A5 gene was carried out in eight Turkish patients from six families. Six patients presented with signs and symptoms of heart failure, cardiomyopathy, and low plasma carnitine levels, five of them with concurrent anemia. A patient with dilated cardiomyopathy had also facial dysmorphia, microcephaly, and developmental delay. Tandem MS analyses in siblings of the patients revealed two more cases with low plasma carnitine levels. SCD diagnosis was confirmed in these two cases by mutation screening. These two cases were asymptomatic but echocardiography revealed left ventricular dilatation in one of them. Carnitine treatment was started before the systemic signs and symptoms developed in these patients. Mean value of serum carnitine levels of the patients was 2.63 AE 1.92 mmol/L at the time of diagnosis. After 1 year of treatment, carnitine values increased to 16.62 AE 5.11 (p < 0.001) and all responded to carnitine supplementation clinically. Mutation screening of the OCTN2 gene study in the patients revealed two novel (p.G411V, p.G152R), and four previously identified mutations (p.R254X, p.R282X, p.R289X, p.T337Pfs12X). Early recognition and carnitine supplementation can be lifesaving in this inborn error of fatty acid oxidation. Abbreviations BNP Brain natriuretic peptide DC Dilated cardiomyopathy EF Ejection fraction HC Hypertrophic cardiomyopathy OCTN2 Organic cation/carnitine transporter SCD Primary systemic carnitine deficiency SLC22A5 Solute carrier family 22 JIMD Reports
The Journal of Pediatrics, 1982
We studied a boy who presented at age 3 89 years with cardiomegaly, a distinctive electrocardiogram, and a history of a brother dying with cardiomyopathy. From age 3 89 to 5 years, cardiac disease progressed, resulting in intractable congestive heart failure. Skeletal muscle weakness developed and a muscle biopsy showed lipid myopathy. Muscle and plasma earnitine were reduced to 2 and 10% of the normal mean values, respectively. Therapy with L-carnitine (174 mg/kg/day) was begun at age 5 89 years and continued to the present (age 6 89 years). The cardiac disease has resolved and the muscle strength has returned to normal. Plasma carnitine concentrations have risen to the low-normal range, while urinary carnitine excretion has increased to values which are 30 times normal. The renal clearance of carnitine exceeds normal at all plasma concentrations and plasma carnitine values do not change acutely after an oral carnitine load. These results suggest that there is a distinct form of carnitine deficiency which presents as cardiomyopathy and may be successfully treated with L-carnitine. A defect in renal and possibly gastrointestinal transport of carnitine is a likely cause of this patient's disorder.
JIMD Reports
Primary carnitine deficiency (PCD) is an inherited disease of fatty acid beta‐oxidation with autosomal recessive inheritance. The disease manifests as metabolic decompensation with hypoketotic hypoglycaemia associated with cardiomyopathy, hepatomegaly, rhabdomyolysis, and seizures. Various outcomes are described from asymptomatic adults to dramatic sudden infant death syndrome cases. We present a severe case of PCD decompensation in an 18‐week‐old female. She presented with hypotonia, moaning, diarrhea, and vomiting at the pediatric emergency. Initially suspected as intracranial hypertension, the clinical condition evolved rapidly and caused a reversible cardiac arrest with profound hypoglycemia. Despite carnitine supplementation, she succumbed from cardiac arrhythmia and multivisceral failure 4 days after admission. The genetic analyses showed a PCD with biallelic pathogenic variants of SLC22A5 gene. The case report is notable for the severity of the cardiac damage possibly favored...
Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype
Solute carrier family 22 member 5 (SLC22A5 ) encodes a sodium-dependent ion transporter responsible for shuffling carnitine across the plasma membrane. This process provides energy for the heart, among other organs allowing beta-oxidation of fatty acids. Mutations in SLC22A5 result in primary carnitine deficiency (PCD), a disorder that manifests with cardiac, skeletal, or metabolic symptoms. We hereby describe two novel mutations in SLC22A5 in two Lebanese families associated exclusively with a cardiac phenotype. The frequency of the cardiac, metabolic and skeletal symptoms in PCD patients remains undefined. All the reported eight PCD patients belonging to five different Lebanese families have an exclusive cardiac phenotype. Carnitine levels appear to be directly linked to the type and position of the mutation and the severity of the phenotypic presentation does not seem to be associated with serum carnitine levels. A comprehensive review of 61 literature-reported PCD cases revealed an exclusive cardiac manifestation frequency at 62.3% with a very low likelihood of simultaneous occurrence of cardiac and metabolic manifestation.
Anesthetic Management of a Patient with 3-Methylcrotonyl-CoA Carboxylase Deficiency
Anesthesia & Analgesia, 2008
Patients with inborn errors of metabolism require special considerations in perioperative care. In the following case report, we describe the successful management of a patient with 3-methylcrotonyl-CoA carboxylase deficiency, a deficit that causes a secondary carnitine deficiency and impaired  oxidation. Patients may have significant underlying cardiomyopathy, and are at risk for metabolic decompensation, acidosis, and hypoglycemia during periods of stress.