"Adult" form of muscular carnitine palmitoyltransferase II deficiency: manifestation in a 2-year-old child

Gempel, Klaus; Praun, Caroline Von; Baumkötter, J.; Lehnert, W.; Ensenauer, Regina; Gerbitz, Klaus-Dieter; Bauer, Matthias

doi:10.1007/s004310100802

Cited by 16 publications

(11 citation statements)

References 9 publications

(14 reference statements)

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“…The clinical features of the adult form have occasionally been reported to occur in childhood, as in the case of a 6-year-old girl who presented with acute muscle weakness, pain, and inability to walk. She had been symptomatic since the age of 2 years and was homozygous for the S113L (338CϾT) mutation that is commonly associated with the adult form of the disease (Gempel et al, 2001). A similar case presenting at 8 months of age was reported by Hurvitz et al (2000).…”

Section: Clinical and Metabolic Features Of Cpt II Deficiencymentioning

confidence: 77%

“…In the adult CPT II deficiencies, carnitine levels are less predictable. Acylcarnitine analysis using tandem mass spectrometry may show elevated long chain (C16 and C18:1) acylcarnitines with low C2 signal (Gempel et al, 2001). LCFA oxidation studies can be performed on cultured fibroblasts, utilizing [9,10-3 H]palmitate and [9,10-3 H]myristate .…”

Section: Diagnosismentioning

confidence: 99%

“…There are some case reports of children with this mutation who present with myopathic features of the adult form of the disease (Gempel et al, 2001). CPT II deficiency may manifest clinically even in a person heterozygous for the S113L mutation (Kaufmann et al, 1997;Taggart et al, 1999;Taroni et al, 1993).…”

Section: Sigauke Et Almentioning

confidence: 99%

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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: Clinical and Metabolic Features Of Cpt II Deficiencymentioning

confidence: 77%

Section: Diagnosismentioning

confidence: 99%

See 1 more Smart Citation

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

Sigauke

Rakheja

Kitson

et al. 2003

Laboratory Investigation

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“…Most of them are males (80%) though the disease is inherited in an autosomal recessive manner. First symptoms most often occur between 6 and 20 years of age, but age at onset may be over 50 years or as early as 8 months in some patients (Gempel et al, 2001;Hurvitz et al, 2000). The symptomatology usually consists of recurrent attacks of myalgias and muscle stiffness or weakness, occasionally associated with myoglobinuria.…”

Section: Cpt2 Deficienciesmentioning

confidence: 97%

Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects

Bonnefont

Djouadi

Prip‐Buus

et al. 2004

Molecular Aspects of Medicine

515

411

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“…The first description was made in 1973 by the brothers Di Mauro. The first symptoms most often occur between 6 and 20 years of age but the age of onset may be over 50 years and as early as 8 months of life [9, 10]. The symptomatology usually consists of recurrent attacks of rhabdomyolysis presenting as myalgias, muscle stiffness and weakness, and myoglobinuria.…”

Section: Introductionmentioning

confidence: 99%

Rhabdomyolysis and Cardiomyopathy in a 20-Year-Old Patient with CPT II Deficiency

Vavlukis

Eftimov

Zafirovska

et al. 2014

Case Reports in Genetics

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Aim. To raise the awareness of adult-onset carnitite palmitoyltransferase II deficiency (CPT II) by describing clinical, biochemical, and genetic features of the disease occurring in early adulthood. Method. Review of the case characteristics and literature review. Results. We report on a 20-year-old man presenting with dyspnea, fatigue, fever, and myoglobinuria. This was the second episode with such symptoms (the previous one being three years earlier). The symptoms occurred after intense physical work, followed by a viral infection resulting in fever treated with NSAIDs. Massive rhabdomyolysis was diagnosed, resulting in acute renal failure necessitating plasmapheresis and hemodialysis, acute hepatic lesion, and respiratory insufficiency. Additionally, our patient had cardiomyopathy with volume overload. After a detailed workup, CPT II deficiency was suspected. We did a sequencing analysis for exons 1, 3, and 4 of the CPT II gene and found that the patient was homozygote for Ser 113 Leu mutation in exon 3 of the CPT II gene. The patient recovery was complete except for the cardiomiopathy with mildly impaired systolic function. Conclusion. Whenever a patient suffers recurrent episodes of myalgia, followed by myoglobinuria due to rhabdomyolysis, we should always consider the possibility of this rare condition. The definitive diagnose of this condition is achieved by genetic testing.

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"Adult" form of muscular carnitine palmitoyltransferase II deficiency: manifestation in a 2-year-old child

Abstract: Carnitine palmitoyltransferase-II deficiency should be included in the differential diagnosis of isolated muscular weakness even when manifesting in early childhood.

Cited by 16 publications

References 9 publications

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

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

Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects

Rhabdomyolysis and Cardiomyopathy in a 20-Year-Old Patient with CPT II Deficiency

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