Table 1

Differential diagnosis of lipid-storage myopathies

Primary carnitine deficiencyNeutral lipid storage disease*MADDSCADDMTPDVLCAD/LCADDCPT2 deficiency†LIPIN1 deficiency
Phenotype Infantile: attacks of vomiting, altered mental status, hypoglycaemia, hepatomegaly (resembling Reye’s syndrome).
Childhood/early adult (more frequent phenotype ): myopathy and hypertrophic/dilated cardiomyopathy.
Others: rhabdomyolysis and respiratory muscle weakness can also occur.
NLSD-Myopathy ( NLSDM ):slowly progressive proximal and distal myopathy, and dilated cardiomyopathy.
NLSD-ichthyosis ( NLSDI ): non-bullous congenital ichthyosiform erythroderma, proximal myopathy (60%) and hepatomegaly.
Neonatal: congenital anomalies, multisystem involvement, death within neonate period.
Childhood: hypoglycaemia, encephalopathy, myopathy, cardiomyopathy.
Adult: progressive proximal myopathy (or rarely exercise intolerance and myoglobinuria).
Others: cardiac, gastrointestinal, hepatomegaly, respiratory failure, dropped-head syndrome, bent-spine syndrome, and sensory axonal polyneuropathy.
Neonatal: Dysmorphic facies, failure to thrive, metabolic acidosis, seizures, myopathy.
Infantile/early adult life: exercise intolerance, myalgias or progressive proximal weakness.
Others: ptosis, progressive external ophthalmoplegia, respiratory muscle weakness, and cardiomyopathy.
Infancy/early childhood: vomiting, altered mental status, hypoketotic hypoglycaemia, hepatopathy, and cardiomyopathy (mortality 50%).
Childhood: progressive weakness and recurrent episodes of myoglobinuria following exercise, illness or fasting.
Others: cardiomyopathy sensorimotor polyneuropathy, and pigmentary retinopathy.
Neonatal: hypertrophic cardiomyopathy and liver failure. High mortality rate (50%–75%).
Infantile: hypoketotic hypoglycaemia as the main feature.
Juvenile/early adult life: e pisodes of myoglobinuria following intense and prolonged exertion, infection, cold or fasting (similar to the adult form of CPT2 deficiency).
Neonatal: encephalopathy, congenital malformations, hepatomegaly and cardiomegaly resulting in death.
Infantile: recurrent attacks of acute liver failure, hypoketotic hypoglycaemia and seizures
Juvenile/ e arly adult life : e pisodes of muscle pain and myoglobinuria following intense and prolonged exertion, infection, cold or fasting.
Recurrent episodes of myoglobinuria in the setting of febrile illness in children.
Creatine kinase1–15×ULN>5×ULN1–20×ULNNormal↑ (Intra-episode)
Free carnitine↓↓↓NormalNormal or slightly reduced (secondary carnitine deficiency)Normal
AC↓↓↓Normal↑ Long-chain, medium-chain and short-chain acylcarnitines↑ Short-chain acylcarnitines↑ Long-chain acylcarnitines (often intra-episode)Normal
Urine organic acidsNormalNormal↑ 2-Hydroxyglutaric acid↑ Ethylmalonic acidNormal (or non-specific abnormalities)
 Muscle biopsy Massive accumulation of lipids in muscle fibres Moderate lipidosis/multi-mini-core Normal (or very mild lipidosis in muscle fibres)
  • PO l-carnitine (100–300 mg/kg/day) for life

  • Intravenous carnitine 100–400 mg/kg/day during life-threatening events

  • Riboflavin (100–400 mg/day) for life

  • CoQ10 supplementation is advised

 … …
  • Supplementation with medium-chain triglycerides in children (controversial in adults)

  • Triheptanoin

  • Agonists of peroxisome proliferator-activated receptors (PPARs)

  • Of note, medium-chain acyl-CoA deficiency (MCAD) is the most common disease of the mitochondrial fatty acid oxidation; however, its myopathic form is extremely rare and therefore it has not been included in this table.

  • *The presence of lipid-containing vacuoles in leucocytes (Jordan’s anomaly) on blood smear is a pathognomonic finding of neutral lipid storage disease (NLSD).

  • †CPT2 deficiency is the most common recognised cause of recurrent rhabdomyolysis in adults.

  • ‡All lipid-storage myopathies shown have an autosomal recessive inheritance pattern.

  • CPT2, carnitine palmitoyl transferase II; LCADD, long-chain acyl-CoA dehydrogenase deficiency; LIPIN, or phosphatidic acid phosphatase deficiency; MADD, multiple acyl-CoA dehydrogenase deficiency; MTPD, mitochondrial trifunctional protein deficiency/long-chain HAD deficiency; NLSD, neutral lipid storage disease; SCADD, short-chain acyl-CoA dehydrogenase deficiency; ULN, upper limit of normal; VLCAD, very-long-chain acyl-CoA dehydrogenase deficiency.