Carnitine metabolism in early stages of Duchenne muscular dystrophy.

Muscle carnitine deficiency was found in 12 children affected with Duchenne muscular dystrophy (DMD), the diagnosis being made at a preclinical stage or at the beginning of the clinical symptoms. Enzymatic activities related to fatty acid transport and carnitine metabolism were studied in these patients and normal subjects: palmitoyl carnitine transferase was increased, palmitoyl carnitine hydrolase was not found in the muscle, palmitoyl coenzyme A synthetase was normal and palmitoyl coenzyme A hydrolase was increased.

[Lipidic myopathy with severe cardiomyopathy caused by a generalized carnitine deficiency. Favourable course during carnitine hydrochloride treatment]. / Myopathie lipidique avec cardiomyopathie sévère par déficit généralisé en carnitine. Evolution favorable sous un traitement par chlorhydrate de carnitine.

The case of a girl who presented with gastrointestinal upsets with nausea, vomiting and occasional hypoglycaemic attacks during childhood is reported. At about 5 years of age generalised muscular weakness with severe amyotrophy, cardiomegaly with a cardiothoracic ratio of 0,63, left ventricular hypertrophy on electrocardiography and left ventricular dilatation with hypokinesis on echocardiography were observed. A few weeks later she developed severe cardiac failure. Muscle biopsy showed muscular dystrophy with lipid infiltration due to carnitine deficiency )serum carnitine 9 nmoles/ml, normal values: 46 +/- 6,9 nmoles/ml; muscle carnitine 0,27 nmoles/mg, normal values: 3,0 +/- 0,79 nmoles/mg fresh frozen weight). She improved rapidly with carnitine chlorhydrate and a diet low in lipids and high in medium chain triglycerides. Regression of muscular symptoms and cardiac failure was observed. After 13 months follow-up with no tonicardiac therapy she is much improved; the signs of heart failure have disappeared, the cardiothoracic ratio is now 0,55 and the electrocardiogramme and echocardiogramme are normal.

Carnitine levels in normal children and adults and in patients with diseases muscle.

An assay for evaluating carnitine levels in normal children and adults is described. After a 12-hour period of fasting, individual variations in 24-hour urinary excretion of carnitine were observed in adults. In children, there was a significant decrease in excretion from the 10th month to the third year, and then an increase until the 10th year. There was no significant difference between children and adults in the serum and skeletal muscle levels. Muscle carnitine levels were also studied in 12 cases of lipid-storage myopathy and in cases of other muscle diseases, including Duchenne muscular dystrophy in children.

[Early clinical and histopathological manifestations in 14 boys showing elevated serum creatine-phosphokinase levels in their first year]. / Manifestations musculaires précoces, cliniques et histopathologiques, chez 14 garcons présentant dans la prèmiere année une activité sérique élévee de créatine-phosphokinase.

The detection of Duchenne muscular dystrophy in the neonate by a determination of the serous activity of CPK allowed the authors to study the muscular, clinical and histopathological features among 14 boys born from 1976 to 1979, showing a raise in the enzymatic activity, confirmed during the first 6 months. 11 boys showed a Duchenne muscular dystrophy, and 3 likely a Becker muscular dystrophy. The authors point out the interest of early findings of hyaline degeneration of the fibers and indicate the variations, from one case to another, of the histopathological evolution in the pre-symptomatic stage. A well examined muscular biopsy is usually conclusive without using an electron microscope, from the age of one year, if serous activity of CPK reaches twenty times the normal rate. If not, waiting for the age of 2 would be advisable, since the initial lesions of the Becker D.M. are not yet clearly defined. When no systematic detection and no familial context, a dosage of the CPK serous activity should be made in the last during the third year, on every boy revealing an unexplained motor retardation. In that purpose, a definition and an application of a motor development score are proposed.

[Systematic neonatal detection of Duchenne's muscular dystrophy. Results after 10 years' of experience in Lyons (France)]. / Dépistage néonatal systématique de la dystrophie musculaire de Duchenne. Bilan après dix ans d'expérience dans la région de Lyon (France).

Neonatal screening of Duchenne Muscular Dystrophy using serum CK level measurement has been performed for 10 years in a part of the Rhône-Alpes area (40,000 newborns per year). This test avoids consecutive cases in an affected family by mean of an early genetic counselling. So, 10 potential DMD boys have been avoided (i.e. one out of five of the D.M.D., as a whole which would be born during this same ten year study). Details on familial structures and efficiency of genetic counselling are given, and this efficiency will be increased by the DNA study of the concerned families.