A Variable Myopathy Associated with Heterozygosity for the R503C Mutation in the Carnitine Palmitoyltransferase II Gene

Vladutiu, Georgirene D.; Bennett, Michael J.; Smail, David; Wong, Lee‐Jun C.; Taggart, R. Thomas; Lindsley, Herbert B.

doi:10.1006/mgme.2000.3009

Cited by 50 publications

(22 citation statements)

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“…Multiple cases of intra and postoperative rhabdomyolysis and renal failure have been reported in patients who have received volatile anesthetics and succinylcholine. [11][12][13] Some of these reactions may be similar in clinical presentation to malignant hyperthermia reactions. It is unclear whether direct effects of the anesthetic medications, the stress of surgery, or perioperative fasting are the key precipitating factors.…”

Section: Discussionmentioning

confidence: 99%

Anesthetic management of a parturient with carnitine palmitoyltransferase ii deficiency

Lilker

Kasodekar

Goldszmidt

2006

Can J Anesth/J Can Anesth

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Purpose: To report the anesthetic management of a patient with carnitine palmitoyltransferase II deficiency who presented for labour and delivery. Clinical features:A 30-yr-old primiparous woman with known carnitine palmitoyltransferase II deficiency and a past history of exercise induced muscle pain, weakness and myoglobinuria presented in active labour. Management consisted of an early epidural for labour and continuous dextrose infusion with frequent blood sugar monitoring. She had an uneventful spontaneous vaginal delivery. She experienced a single asymptomatic episode of hypoglycemia on the first postpartum day. Her serum creatine kinase was six times normal at 24 hr postdelivery and remained elevated for three days without evidence of rhabdomyolysis. The remainder of her postpartum course was uneventful. Conclusion:Labour and delivery is a potential precipitant of rhabdomyolysis in patients with carnitine palmitoyltransferase II deficiency. The normal postpartum creatine kinase elevation (two to four times baseline at 24 hr) must be taken into account when monitoring these patients. On the basis of the physiologic principles, institution of early epidural analgesia to blunt the stress response to labour and delivery, continuous dextrose infusion and frequent glucose monitoring during labour and postpartum are the mainstays of management. Objectif

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Section: Discussionmentioning

confidence: 99%

Anesthetic management of a parturient with carnitine palmitoyltransferase ii deficiency

Lilker

Kasodekar

Goldszmidt

2006

Can J Anesth/J Can Anesth

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“…Proper biochemical investigations, carnitine palmitoyl transferase (CPT) and carnitine [1], glycolitic pathway [2], acid maltase [9], mitochondrial enzyme activity [4] and β-oxidation essays [37], were performed following the diagnostic clues offered by morphological analysis. In 41 cases genetic studies were necessary to try to make a diagnosis: in 14 cases analysis of dystrophin gene [5], in 4 of CPT gene [38], in 3 of the ryanodine receptor gene [23], in 4 for Steinert myotonic dystrophy [28], in 5 of mitochondrial DNA [4]. At Needle EMG examination our cases fit into one of four neurophysiological patterns: normal, myopathic, neurogenic and mixed pattern [16].…”

Section: Clinical and Laboratory Evaluationmentioning

confidence: 99%

Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels

Prelle¹,

Tancredi²,

Sciacco³

et al. 2002

Journal of Neurology

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“…The R503C (1507CϾT), and G549D (1646GϾA) substitutions are located in highly conserved regions of all CPT genes. The R503C mutation, which is lethal in the homozygous state, is known to cause clinical symptoms in the simple heterozygous form (Taggart et al, 1999;Vladutiu et al, 2000).…”

Section: Sigauke Et Almentioning

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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A Variable Myopathy Associated with Heterozygosity for the R503C Mutation in the Carnitine Palmitoyltransferase II Gene

Cited by 50 publications

References 35 publications

Anesthetic management of a parturient with carnitine palmitoyltransferase ii deficiency

Anesthetic management of a parturient with carnitine palmitoyltransferase ii deficiency

Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels

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

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