Lipid Storage Myopathy Responsive to Prednisone

Engel, Andrew G.; Siekert, Robert G.

doi:10.1001/archneur.1972.00490140078011

Cited by 68 publications

(22 citation statements)

References 12 publications

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“…We studied one MCD patient, four SCD patients, and six normal volunteers. The MCD patient was a 32-yr-old woman whose clinical history was described previously (2,3,14). SCD patients were a 6-yr-old male, an 8.5-yr-old female, and two sisters, 3.8 and 6.2 yr old.…”

Section: Methodsmentioning

confidence: 99%

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

Rebouche

Engel²

1984

J. Clin. Invest.

172

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Abstract. The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A threecompartment model (extracellular fluid, muscle, and "other tissues") was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results ofthese calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process.Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation ofthe muscle/plasma carnitine concentration gradient.Received for publication 27 June 1983 and in revised form 21 October 1983.In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract.

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Section: Methodsmentioning

confidence: 99%

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

Rebouche

Engel²

1984

J. Clin. Invest.

172

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“…Carnitine assays in muscle, liver, and plasma of the patient and parents are summarized in table 1 . Before carnitine administration the patient's muscle contained only traces of free carnitine; in the plasma and liver it was reduced to about 12 percent of the mean control level.…”

Section: Materials and Methods Biopsies Of The Left Vastusmentioning

confidence: 99%

The syndrome of systemic carnitine deficiency

Karpati¹,

Carpenter²,

Engel³

et al. 1975

Neurology

Self Cite

375

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An 11 -year-old boy had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped musculature. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. Hypertrophied smooth endoplasmic reticulum and excessive microbodies were present in liver. Marked carnitine deficiency was shown in skeletal muscle, plasma, and liver. Ketogenesis was impaired on a high fat diet, but omega oxidation of fatty acids was enhanced. There was excessive glucose uptake and essentially no oxidation of labeled long-chain fatty acids by perfused forearm muscles in vivo. Oral replacement therapy restored plasma carnitine levels to normal, but not liver or muscle carnitine levels, and was accompanied by clinical improvement.The syndrome of systemic carnitine deficiency Clinical, morphologic, biochemical, and pathophysiologic features n 1972 Engel and Siekert described an unusual I variety of lipid storage myopathy in a 24-year-old woman. * The unusual features included a striking beneficial response to corticosteroid therapy and the c o e x i s t e n c e of a b n o r m a l l i v e r f u n c t i o n t e s t s . Subsequently, Engel and Angelini found that the skeletal muscle of this patient had a very low level of carnitine, and in vifro oxidation of fatty acids by her muscle was considerably reduced. 2 -3 This patient was the first recognized human example of carnitine deficiency. Since that report, at least four other patients have been identified. [4][5][6][7] This paper is a detailed report of a patient with systemic carnitine d e f i~i e n c y ,~ with special attention to the vaned clinical, morphologic, biochemical, and metabolic features of this disorder. Dr. Karpati's address is Montreal Neurological Institute, 3801 University St., Montreal, Que., Canada H3A 284.Case report. This 1 1-year-old boy was born after a full term uneventful pregnancy and delivery. Birth weight was 7 Ib. Milestones of his psychomotor development were normal, but according to his mother, he was always a "weak and clumsy child" and his neck and head were always "floppy."At age three and one-half years, the patient was hospitalized with acutely developing vomiting and a major convulsive seizure. Cerebrospinal fluid was normal, as was serum calcium. His blood sugar was reduced initially to 27 mg percent but subsequently was found to be normal on several occasions. He had some abnormal liver function tests; serum glutamic oxaloacetic transaminase (SGOT) 103 units (normal, less than 30) and serum glutamic pyruvic transaminase (SGPT) 125 units (normal, less than 1 5 units), but serum bilirubin was normal. An electroencephalogram (EEG) showed a diffuse, high amplitude dysrhythmia. The cause of the acute encephalopathy and the abnormal liver function tests was not established and the child's clinical status, EEG, and liver function tests returned to normal.The patient started school at age six, but after completing grades 1 and 2 he had difficulties with writing and spelling. Psychometric evaluation reveal...

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“…Lipid accumulations within skeletal mus cle have been reported in mitochondrial my opathy [22,35], carnitine deficiency [ 15], py ruvate decarboxylase deficiency [10], inabil ity to utilize long-chain fatty acids [ 13] and in defective oxidative metabolism of fatty acids [ 14]. Obviously, our patient does not belong to any of these conditions.…”

Section: Discussionmentioning

confidence: 75%

Postganglionic Cholinergic Dysautonomia; Report of Muscle Findings in 1 Case

Afifi¹,

Harik²,

Bergman³

et al. 1982

Eur Neurol

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Heretofore unreported findings in skeletal muscle in a 4th case of pure postganglionic dysautonomia are described. They consist of variation in fiber size, Z line and myofilamentous disorganization, intracytoplasmic inclusions and honeycomb formations. The most striking alteration, however, was excess lipid accumulation without concomitant mitochondrial alterations. Sural nerve histology and cytology were normal. The mechanism of lipid accumulation in skeletal muscle of patients with dysautonomia remains unexplained.

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Lipid Storage Myopathy Responsive to Prednisone

Cited by 68 publications

References 12 publications

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

The syndrome of systemic carnitine deficiency

Postganglionic Cholinergic Dysautonomia; Report of Muscle Findings in 1 Case

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