Carnitine palmityl transferase deficiency

Angelini, C.; Freddo, Lorenza; Battistella, Pierantonio; Bresolin, Nereo; Pierobon-Bormioli, Sandra; Armani, Mario; Vergani, L

doi:10.1212/wnl.31.7.883

Cited by 54 publications

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“…It is an autosomal recessive disorder (Angelini et al, 1981;Meola et al, 1987) and is now regarded as one of the most common inherited disorders of lipid metabolism . Isolated presentation in two successive generations has been reported, indicating a possible dominant inheritance (Mongini et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review

Sigauke

Rakheja

Kitson

et al. 2003

Laboratory Investigation

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SUMMARY:Congenital deficiency of carnitine palmitoyltransferase (CPT) II has been known for at least 30 years now, and its phenotypic variability remains fascinating. Three distinct clinical entities have been described, the adult, the infantile, and the perinatal, all with an autosomal recessive inheritance pattern. The adult CPT II clinical phenotype is somewhat benign and requires additional external triggers such as high-intensity exercise before the predominantly myopathic symptoms are elicited. The perinatal and infantile forms involve multiple organ systems. The perinatal disease is the most severe form and is invariably fatal. The introduction of mass spectrometry to analyze blood acylcarnitine profiles has revolutionized the diagnosis of fatty acid oxidation disorders including CPT II deficiency. Its use in expanded neonatal screening programs has made presymptomatic diagnosis a reality. An increasing number of mutations are being identified in the CPT II gene with a distinct genotype-phenotype correlation in most cases. However, clinical variability in some patients suggests additional genetic or environmental modifiers. Herein, we present a new case of lethal perinatal CPT II deficiency with a rare missense mutation, R296Q (907GϾA) associated with a previously described 25-bp deletion on the second allele. We review the clinical features, the diagnostic protocol including expanded neonatal screening, the treatment, and the biochemical and molecular basis of CPT II deficiency. (Lab Invest 2003, 83:1543-1554.T he carnitine palmitoyltransferase (CPT) enzyme system, in association with acyl-coenzyme A (CoA) synthetase and the carnitine-acylcarnitine translocase (CACT), plays an important role in the transfer of long chain fatty acids (LCFA) from the cytosolic compartment to the mitochondrial matrix, where ␤-oxidation occurs (Bieber, 1988). Two genetically distinct mitochondrial membrane-bound enzymes make up the CPT system. CPT I is located on the inner aspect of the outer mitochondrial membrane. This enzyme is physiologically inhibited by the high levels of malonyl-CoA that occur postprandially and thus regulates the entry of LCFA into the mitochondria (McGarry and Brown, 1997). CPT II, which is not inhibited by malonyl-CoA, is situated on the inner aspect of the inner mitochondrial membrane (Murthy and Pande, 1987).CPT II deficiency was first reported by DiMauro and DiMauro (1973) in adults with exercise-induced rhabdomyolysis. It is an autosomal recessive disorder (Angelini et al, 1981;Meola et al, 1987) and is now regarded as one of the most common inherited disorders of lipid metabolism . Isolated presentation in two successive generations has been reported, indicating a possible dominant inheritance (Mongini et al, 1991). Partial CPT II deficiency with an autosomal dominant inheritance pattern has also been reported (Ionasescu et al, 1980). The molecular basis for this presentation was not elucidated.To date, three distinct CPT II-deficient phenotypes have been described in the literature, for wh...

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Section: Discussionmentioning

confidence: 99%

Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review

Sigauke

Rakheja

Kitson

et al. 2003

Laboratory Investigation

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“…There are several reports of CPT deficiency in muscle (see [11,12]); of these, one case was thought to be a defect of CPT I and a number to be defects of CPT II [10,[20][21][22][23][24][25][26][27][28]. The interpretation of these reports is often uncertain because of the different assays used.…”

Section: Discussionmentioning

confidence: 99%

A case of carnitine palmitoyltransferase II deficiency in human skeletal muscle

et al. 1988

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A 20-year-old man was shown to have a deficiency of carnitine palmitoyltransferase (CPT) II in skeletal muscle. The evidence was: (i) there was no significant oxidation of [9,10 -3 H]palmitate or of[1-14C]palmitate in mitochondrial fractions from fresh skeletal muscle from the patient; (ii) all the CPT activity in a homogenate of fresh muscle from the patient was overt (CPT I) with no increase in activity after the inner membrane was disrupted; (iii) all the CPT activity in the patient's muscle was inhibited by malonyl-CoA; and (iv) an immunoreactive peptide of 67 kDa corresponding to CPT II, present in mitochondria from controls, was absent in those from the patient.Carnitine palmitoyltransferase deficiency; Carnitine palmitoyltransferase II; Mitochondria; (Skeletal muscle)

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“…Nas desordens inatas do metabolismo lipídico, o metabolismo de carboidratos não se altera mas a utilização dos ácidos graxos fica limitada, permanecendo o paciente todo o tempo num potencial "dé-ficit energético", justamente pela baixa capacidade de oxidação de lipídios 7,11,[14][15][16] . Nesses casos, qualquer situação de grande demanda metabólica, associada a uma reduzida capacidade de sintetizar ATP e fosfatos de alta energia, culmina em dificuldade de manter a integridade da membrana celular, quando ocorre a citólise e se deflagra a mioglobinúria.…”

Section: Discussionunclassified

“…Também, os exames laboratoriais, a eletroneuromiografia, e a biópsia muscular podem não apresentar alterações nos períodos de acalmia 1,3,4,11,15,16 . O diagnóstico definitivo é selado através das dosagens séricas, e do estudo histoquímico e bioquímico de homogenados musculares, quantificando as atividades enzimáticas 1,3,4,6,11,14,17 , o que não foi possível de se realizar com esse paciente.…”

Section: Discussionunclassified

Insuficiências respiratória e renal desencadeadas por miopatia metabólica por acúmulo de lipídios: relato de caso

Filho

Nicolini

Martins

et al. 2002

Arq. Neuro-Psiquiatr.

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RESUMO -Relatamos o caso de um paciente de 26 anos que apresentou quadro clínico de rabdomiólise e mioglobinúria associadas a insuficiência renal e respiratória, três dias após o início de infecção de vias aéreas superiores. Os dados clínicos e laboratoriais, eletroneuromiografia e biópsia muscular conduziram ao diagnóstico de miopatia metabólica por deficiência enzimática relacionada ao metabolismo dos ácidos graxos. O paciente evoluiu favoravelmente com a instituição de suporte avançado de vida, incluindo assistência ventilatória e terapia dialítica, adequação dietética e reposição de L-carnitina. Discorremos sobre as diversas miopatias metabólicas, o diagnóstico, o diagnóstico diferencial e o tratamento.PALAVRAS-CHAVE: metabolismo de lipídeos, metabolismo do glicogênio, rabdomiólise, miopatia metabólica, deficiência de carnitina palmitil transferase.Respiratory and renal dysfunctions due to lipid storage metabolic myopathy: case report Respiratory and renal dysfunctions due to lipid storage metabolic myopathy: case report Respiratory and renal dysfunctions due to lipid storage metabolic myopathy: case report Respiratory and renal dysfunctions due to lipid storage metabolic myopathy: case report Respiratory and renal dysfunctions due to lipid storage metabolic myopathy: case report ABSTRACT -We report a case of a 26-years old male patient with rhabdomyolisis with myoglobinuria associated with acute renal and respiratory failure, that occurred three days after upper airway infection. In the clinical and laboratory investigation of the patient, including electromyography and muscular biopsy, the diagnostic lead to a metabolic myopathy due to an enzymatic deficiency related to a disorder of lipid metabolism. The patient improved successfully with institution of advanced life support, including ventilatory assistence, dialysis, dietary adjust and L-carnitine reposition.KEY WORDS: lipid metabolism, glycogen metabolism, rhabdomyolysis, myoglobinuria, metabolic myopathy, carnitine palmityl transferase deficiency. Os lipídios musculares cada vez mais têm recebido atenção devido seu papel como fonte de energia e o conhecimento de seu metabolismo levou à descrição de doenças decorrentes de defeitos na sua utilização 1,2 . Em geral, essas patologias apresentam relação entre miopatia e alteração no metabolismo lipídico. A deficiência enzimática proporciona alteração metabólica em que há limitação na utilização de lipídios como fonte de energia pela célula 1,3,4 . Expressão clínica mais importante desta deficiência são episódios recorrentes de rabdomiólise com mioglobinúria, precipitados principalmente por exercício extenuante 1,[3][4][5][6] . Entre outras causas que podem desencadear a lise muscular estão a exposição ao frio, privação de sono, jejum prolongado, anestesia e infecções 7,8 . O objetivo deste estudo é relatar o caso de um paciente com deficiência enzimática relacionada ao metabolismo de lipídio diante de situação de alta demanda metabólica, e alertar para um grupo de patologias em que o alto índice de suspeiç...

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Carnitine palmityl transferase deficiency

Cited by 54 publications

References 0 publications

Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review

Carnitine Palmitoyltransferase II Deficiency: A Clinical, Biochemical, and Molecular Review

A case of carnitine palmitoyltransferase II deficiency in human skeletal muscle

Insuficiências respiratória e renal desencadeadas por miopatia metabólica por acúmulo de lipídios: relato de caso

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