CPT-II deficiency

Inherited CPT-I deficiency affects only the fiver, resulting in reduced fatty acid oxidation and ketogenesis, witfi fiypoglycemia. CPT-II deficiency affects pri-... 

CPT-II deficiency is more common and mainly manifests as muscle weakness, myoglobinemia, and myoglobinuria upon exercise severe cases lead to hyperketotic hypoglycemia, hyperammonemia, and death. 

The answer is D. The most likely diagnosis in this case is CPT-II deficiency, although this is apparently a fairly mild case. The patient s muscle weakness and brown urine (myoglobinuria) are characteristic of this disorder. CPT-I deficiency would most likely manifest as liver dysfunction. A secondary form of carnitine deficiency due to exogenous factors such as malnutrition, infection, or dialysis, is unlikely. MCAD ordinarily manifests within the first 3-5 years of life. The patient s normal stature is inconsistent with Marfan syndrome, which is characterized by tall stature and very long bones in the extremities. 

In 1955, Fritz determined that carnitine plays an essential role in fatty acid -oxidation (FAO), and in 1973 the first two clinically relevant disorders affecting this pathway were described primary carnitine deficiency by Engel and Angelini, and carnitine palmitoyltransferase (CPT) type II (CPT-II) deficiency by DiMauro and DiMauro [6, 7]. To date, more than 20 different enzyme deficiency states affecting fatty acid transport and mitochondrial / -oxidaLion have been described [8] and additional enzymes involved in this pathway are still being discovered [9, 10]. 

The long-chain FAO disorders of CACT deficiency and CPT-II deficiency can not be differentiated because both cause accumulation of the same long-chain acylcarnitine species, which is explained by the fact that neither enzyme is involved in the chain-shortening action of FAO (Table 3.2.1 Fig. 3.2.6e and f). Isolated long-chain... 

Clinical problems related to fatty acid metabolism. Deficiencies in carnitine lead to an inability to transport fatty acids into the mitochondria for oxidation. This can occur in newborns and particularly in pre-term infants. Treatment is by oral carnitine administration. Carnitine palmitoyltransferase I (CPT I) deficiency primarily affects the liver and leads to reduced fatty acid oxidation and ketogenesis. CPT II deficiency results in recurrent muscle pain, fatigue and myoglobinuria following strenuous exercise. 

CPT-II deficiency 600649 600650 Carnitine palmitoyl transferase II <1 100,000 Cardiomyopathy, liver disease, congenital anomalies. Adult onset myopathy. ... 

Whereas adults with deficiency of CPT II have a disorder characterised by exercise intolerance and myoglobinuria, the same deficiency in new-boms is a generalised lethal disease with reduced CPT II activity in multiple organs. Distinct genetic variations have been described for both disorders. In this review article we will report the current knowledge of the molecular genetic background of both types of CPT II deficiency. 

Particularly common among Europeans with the classical adult muscular form of the disorder is a C --> T transition at nucleotide 439 which changes amino acid 113 fi-om serine to leucine. It was first described by Taroni et al in 1993 and in subsequent studies it was shown that this mutation can be found in approximately 60% of all alleles. It is therefore called the common CPT II deficiency mutation. ... 

In summary, to date there is neither a plausible concept of how different mutations in the same gene cause such disparate clinical symptomatology of the disease on one hand (lethal-neonatal versus adult-onset) nor how such different residual activities of this enzyme lead to comparably similar phenotypes (adult-onset muscular) on the other hand. A variable degree of reduction of CPT activity, variable posttranslational modifications of the enzyme in different tissues, a disturbance of regulatory properties of the CPT system or a variable efHeiency of further distal eomponents of the P-oxidationmachin-ery by an pathologieally altered enzyme might determine the difference in clinical severity of the different forms of CPT II deficiency. 

The first described inborn error of fatty acid oxidation was muscle CPT II deficiency, which was reported in 1973. MCAD deficiency is the most frequent FAO disorder, with a prevalence of 1 in 12000 to 20000 in Caucasians from northern Europe. 

Palmitoyl (Cl6 P, B T VLCAD deficiency CPT-II deficiency CAT deficiency LCHAD deficiency MAD deficiency... 

VLCAD deficiency CPT-II deficiency CAT deficiency LCHAD deficiency... 

In 1995 an exceptional case of neonatal CPT II deficiency was published, which presented as a lethal myopathy. The common metabolic features of the lethal infantile form were absent. 

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