Nelson Textbook of Pediatrics 22nd Edition โ Disorders of fatty acid oxidation and carnitine metabolism. CPT2 deficiency (most common cause of recurrent myoglobinuria), VLCAD deficiency, primary systemic carnitine deficiency (SLC22A5), MADD (ETFDH, multiple acyl-CoA dehydrogenase deficiency). Triggers: fasting, prolonged exercise, cold, high-fat meals, infection. Diagnosis: acylcarnitine profile, muscle biopsy (lipid droplets), genetic testing.
๐ paeds.online โ Pakistan's Pediatric Platform| Disorder | Gene | Acylcarnitine Pattern | Triggers | Baseline CK | Treatment |
|---|---|---|---|---|---|
| CPT2 deficiency | CPT2 | C16, C18:1 elevated | Prolonged exercise, fasting, cold, high-fat meal, febrile illness | Normal | Low-fat diet, avoid fasting, IV glucose during illness, carnitine, medium-chain triglycerides (MCT) |
| VLCAD deficiency | ACADVL | C14:1 elevated | Fasting, prolonged exercise, cold, fever | Normal | Avoid fasting, MCT oil, carnitine, IV glucose during illness |
| Primary systemic carnitine deficiency | SLC22A5 (OCTN2) | Low free carnitine, low acylcarnitines | Hypoglycemia, cardiomyopathy, weakness | Normal-mild elevation | Oral L-carnitine (100-400 mg/kg/day), avoid fasting |
| Muscle carnitine deficiency | Unknown (SLC22A5 usually systemic) | Normal serum carnitine, low muscle carnitine | Progressive proximal weakness | Mild elevation | Oral L-carnitine (variable response) |
| Multiple acyl-CoA dehydrogenase deficiency (MADD) | ETFDH, ETFA, ETFB | Multiple acyl-carnitines (C4-C18:1) | Exercise, fasting, infection | Mild-moderate elevation | Riboflavin (some responsive), carnitine, low-fat diet, avoid fasting |
| LCHAD / TFP deficiency | HADHA, HADHB | 3-hydroxy C16, C18 acylcarnitines | Hypoglycemia, cardiomyopathy, rhabdomyolysis | Normal | Low-fat diet, MCT, avoid fasting, carnitine |
| MCAD deficiency | ACADM | C8 elevated | Fasting (hypoglycemia), less myopathy | Normal | Avoid fasting, cornstarch, IV glucose during illness |
History: Recurrent rhabdomyolysis (myoglobinuria, CK >10,000) triggered by fasting, prolonged exercise, cold, high-fat meal, febrile illness. Normal baseline CK between episodes.
Acylcarnitine profile (blood spot): Key diagnostic test. Elevations of specific species (C14:1 in VLCAD, C16/C18:1 in CPT2, low free carnitine in systemic carnitine deficiency).
Muscle biopsy: Increased lipid droplets (oil red O stain) in type I fibers.
Treatment principles: Avoid fasting, avoid high-fat meals (for CPT2/VLCAD), maintain glucose during illness (IV D10), MCT oil (bypasses long-chain FAO defects), carnitine supplementation (except in CPT2? careful โ can increase acylcarnitines; usually safe, but evidence limited).