Genotype/phenotype correlation in carnitine palmitoyl transferase II deficiency: lessons from a compound heterozygous patient

Thuillier, Laure; Sevin, Caroline; Demaugre, F.; Brivet, M.; Rabier, Daniel; Droin, Véronique; Aupetit, J.; Abadi, Nourredine; Kamoun, P.; Saudubray, Jean Marie; Bonnefont, Jean‐Paul

doi:10.1016/s0960-8966(99)00096-6

Cited by 25 publications

(32 citation statements)

References 29 publications

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“…CPT-II deficiency can be categorized as the myopathic form (OMIM: 255110), the early infantile hepatocardiomuscular form (OMIM: 600649), or the lethal neonatal form (OMIM: 608836) with multisystem involvement (Bonnefont et al 2004). Patients with the myopathic form present with rhabdomyolysis, which may be complicated by life-threatening events, including acute renal failure from myoglobinuria, respiratory insufficiency due to diaphragm involvement (Smolle et al 2001), and paroxysmal cardiac arrhythmia (Thuillier et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Missed Newborn Screening Case of Carnitine Palmitoyltransferase-II Deficiency

et al. 2016

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Carnitine palmitoyltransferase-II (CPT-II) deficiency can be detected through newborn screening with tandem mass spectrometry. We report a 4-year-old patient with rhabdomyolysis due to CPT-II deficiency, which was initially missed by newborn screening. The patient presented with a 2-day history of fevers, upper respiratory infection, diffuse myalgia, and tea-colored urine. Her medical history was notable for frequent diffuse myalgia when ill. She was demonstrated to have homozygous mutation c.338C>T, p. S113L in CPT2, which is typically found in the adult-onset, myopathic form of the disease. An unknown number of CPT-II deficient patients with normal newborn screening have not yet presented to medical care with the adult-onset, myopathic form of disease. We conclude that (1) not all cases of CPT-II deficiency are currently detected through newborn screening, even when blood is appropriately collected on day 2 of life and (2) CPT-II deficiency should be kept on the differential for patients presenting with rhabdomyolysis, even if the newborn screening results were normal.

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Section: Introductionmentioning

confidence: 99%

Missed Newborn Screening Case of Carnitine Palmitoyltransferase-II Deficiency

et al. 2016

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“…Although the genotype has clearly been associated with disease severity in many cases of CPT II deficiency, it is becoming accepted that the best predictive indicator may be the residual level of LCFA oxidation, typically performed in cultured cells (Thuillier et al, 2000). Three polymorphisms have been described, the V368I (1203GϾA), for which our patient was homozygous, the M647V (2040AϾG) substitution , and the F352C (1571TϾG) substitution, which is predominantly found in the Japanese population (Wataya et al, 1998).…”

Section: Sigauke Et Almentioning

confidence: 84%

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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“…The present study demonstrated that the expression of CPT-II mRNA in the heart was significantly higher in Trained rats compared with Control rats. CPT-II is involved in the transfer of long-chain FA into the mitochondrial matrix (44), and changes in the mRNA expression and activity of CPT-II affect FA metabolism (45,46). Furthermore, it has been reported that the increase in mRNA expression of CPT II in the skeletal muscle was induced by exercise training with increased contractile activity in the skeletal muscle (47).…”

Section: Fig 4 Expression Of Phosphofructokinase (Pfk) Mrna In the mentioning

confidence: 99%

Cardiac Hypertrophy by Hypertension and Exercise Training Exhibits Different Gene Expression of Enzymes in Energy Metabolism

et al. 2003

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Genotype/phenotype correlation in carnitine palmitoyl transferase II deficiency: lessons from a compound heterozygous patient

Cited by 25 publications

References 29 publications

Missed Newborn Screening Case of Carnitine Palmitoyltransferase-II Deficiency

Missed Newborn Screening Case of Carnitine Palmitoyltransferase-II Deficiency

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

Cardiac Hypertrophy by Hypertension and Exercise Training Exhibits Different Gene Expression of Enzymes in Energy Metabolism

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