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Postpartum manifestation of a necrotising lipid storage myopathy associated with muscle carnitine deficiency
  1. Department of Neurology
  2. Department of Neuropathology, Heinrich-Heine University, PO Box 101007, D 40001 Düsseldorf, Germany
  1. Dr Hubertus Köller, Department of Neurology, Heinrich-Heine University, PO Box 101007, D 40001 Düsseldorf, Germany.
  1. Department of Neurology
  2. Department of Neuropathology, Heinrich-Heine University, PO Box 101007, D 40001 Düsseldorf, Germany
  1. Dr Hubertus Köller, Department of Neurology, Heinrich-Heine University, PO Box 101007, D 40001 Düsseldorf, Germany.

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Carnitine deficiency as a cause of lipid storage myopathy originates from a defect of carnitine transport into muscle cells.1 Secondary carnitine deficiency with lipid storage myopathy2 can be a result of genetic defects of intermediary metabolism, especially mitochondrial respiratory chain defects, defects of β-oxidation enzymes, or drug therapy—for example, valproate or pivampicillin. A transient systemic carnitine deficiency regularly occurs during pregnancy even in healthy women. At delivery, decreased plasma carnitine concentrations are in the same range as in patients with inborn carnitine deficiency.3

We report a 24 year old woman in good health without any previous episodes of muscle weakness or metabolic crises who experienced a slowly progressive weakness of proximal muscles after delivery. The pregnancy and delivery had been uneventful other than the necessity for a caesarean section due to placental insufficiency. She did not receive any medication during pregnancy or after delivery with the exception of the nitrous oxide-oxygen-isoflurane anaesthesia in combination with vecuronium bromide, suxamethonium chloride, codeine, and fentanyl. Atropine and theophylline were given during the first hours after the section.

The muscular weakness was first noticed three months after delivery and increased to a so far stable deficit with only slight fluctuations within the next six months. The weakness of her proximal arm and leg muscles prevented her lifting her arm above her head and impaired stair climbing. There was no muscle pain, no myoglobinuria, and no sensory deficits.

The patient was first seen in our department six months after the onset of weakness. She had pronounced symmetric weakness of proximal muscles of the arms, legs, and neck without muscle pain and sensory deficits. Muscle enzymes were still greatly increased: creatine phosphokinase 720 U/l (normal<70 U/l), lactic dehydrogenase 543 U/l (normal<240 U/l), glutamic oxaloacetic transaminase 32 U/l (normal<15 U/l). Erythrocyte sedimentation rate was normal (6 mm in the first hour). Needle EMG showed spontaneous fibrillation in the deltoid and rectus femoris muscle. Motor units were of short duration, small amplitude, polyphasic, and showed a dense interference pattern on submaximal effort. Her ECG, chest radiography, and echocardiogram were normal. In her family history neither her parents nor her two brothers nor any other member of the family had muscle weakness.

A biopsy of the left deltoid muscle disclosed severe necrotising myopathy with pronounced atrophy predominantly of type 2 fibres, widespread regenerating fibres, scattered fibre necroses undergoing phagocytosis, single ghost fibres, and few ragged-red-fibres. There was pronounced endomysial fibrosis reflecting the chronicity of the disease. Signs of inflammation were not present. Histochemical stains disclosed prominent storage of lipid droplets in the muscle fibres. In addition, single fibres showed slightly reduced activity of cytochrome c oxidase. The lipid storage myopathy was confirmed by electron microscopy; the mitochondria were ultrastructurally normal.

Biochemical studies of muscle tissue showed a reduction of total carnitine to 15.1 μmol/g of non-collagenous protein (NCP, reference value 21.0–43.1 μmol/g NCP) and free carnitine to 11.9 μmol/g NCP (reference value 19.5–35.1 μmol/g NCP). Acylcarnitine was normal (3.2 μmol/g NCP, reference value 0.5–13.4 μmol/g NCP) as well as mitochondrial enzymes (carnitine palmitoyl transferase, NADH coenzyme Q reductase, cytochrome c oxidase, succinate/cytochrome c oxidoreductase). Southern blot analysis of mitochondrial DNA showed a single population of mitochondrial DNA molecules. Point mutations typical for MELAS, MERRF, and Leigh disease could be excluded. Plasma carnitine concentrations were normal: 35.1 μmol/l (normal 25–64 μmol/l).

After diagnosis of muscular carnitine deficiency a treatment was started with 4 g carnitine/day orally. After 11 months of therapy, there was no increase in muscle strength and no decrease in the high plasma concentrations of muscle enzymes but her condition was stable.

Carnitine contributes to muscular energy supply by controlling the influx of long chain fatty acids into mitochondria and a carnitine deficiency myopathy is often secondary to mitochondrial enzyme defects.

Lipid storage is the predominant histological manifestation in carnitine deficiency.1 4 In our case additional and unusual features such as severe muscle fibre necrosis and a few ragged-red-fibres were seen. Necrotic and regenerating muscle fibres have occasionally been described after acute phases of deterioration in carnitine deficiency.2 Lipid storage in combination with ragged-red fibres is suggestive of a respiratory chain defect with secondary carnitine deficiency.5 Although few ragged-red fibres were present in the muscle biopsy of our patient further biochemical analysis excluded a respiratory chain defect. Moreover, mutations for MELAS and Leigh’s disease as well as drug therapy causing carnitine deficiency could be excluded. Defects of β-oxidation enzymes which can mimic primary carnitine deficiency2 seems to be unlikely as there were no episodes of metabolic crisis or hepatic dysfunction.

The myopathy in our patient occurred after her first pregnancy. To our knowledge, the clinical course of lipid storage myopathies during and after pregnancy has been reported in only three cases (table). Two patients showed a deterioration of a prediagnosed myopathy4 6 whereas one woman experienced the manifestation of a lipid storage myopathy with decreased concentrations of muscle and plasma carnitine after delivery.7 The muscle weakness started some weeks after delivery and reached a peak within several months (table). Two other patients with mitochondrial myopathies (one with an unidentified enzyme defect,8 one with carnitine palmitoyl transferase deficiency9) were asymptomatic during pregnancy and after delivery.

Course of lipid storage myopathies during pregnancy and after delivery

Our case again stresses that pregnancy may precipitate the manifestation of lipid storage myopathy. Plasma carnitine concentrations are regularly decreased at the end of pregnancy.3 7 Normal plasma carnitine concentrations are reached within one month after delivery. However, in patients with carnitine deficiency muscular carnitine stores are not replenished by increased plasma carnitine.1 2 7 Therefore, a prolonged decrease in plasma carnitine concentrations during pregnancy may critically reduce muscular carnitine in patients with a latent carnitine deficiency who seem to be unable to compensate the temporary deficiency. A lipid storage myopathy may then become clinically manifest.


We thank Professor K Gerbitz and his coworkers (Institut für klinische Chemie, Städtisches Krankenhaus München-Schwabing, Munich) for performing the biochemistry and mitochondrial DNA analyses and Professor H Reichmann, Dresden, for helpful discussions.