Carnitine-acylcarnitine translocase deficiency (CACT)
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A neonate presents in the first 48 hours of life with seizures, cardiac arrhythmia, hypoketotic hypoglycemia, and hyperammonemia. Acylcarnitine profile shows markedly elevated C16, C18, and C18:1 with low free carnitine.
AR; SLC25A20 (carnitine-acylcarnitine translocase on the inner mitochondrial membrane). Translocates long-chain acylcarnitines into the matrix in exchange for free carnitine.
- Severe neonatal-lethal phenotype is the rule: cardiomyopathy, arrhythmia (often ventricular), hyperammonemia, hypoketotic hypoglycemia, liver failure
- Milder later-onset forms exist but are rare
- Acylcarnitine profile resembles CPT2 (elevated long-chain species) and is not distinguishable on NBS alone; genetic testing confirms
- Newborn screening (RUSP) acylcarnitine profile: elevated long-chain species (C16, C18, C18:1) with low free carnitine (C0)
- Profile is indistinguishable from CPT2 deficiency; the two cannot be separated biochemically
- Confirmatory SLC25A20 molecular testing distinguishes CACT from CPT2 (fibroblast/leukocyte enzyme studies can supplement)
- Avoid fasting; aggressive emergency IV glucose
- MCT-rich, low long-chain-fat diet
- Carnitine supplementation is controversial (may worsen arrhythmia)
- Most severe cases do not survive infancy despite treatment
"CACT carts the cargo across." The translocase shuttles long-chain acylcarnitines across the inner mitochondrial membrane. When the cart breaks, fatty acids cannot reach the matrix to be oxidized; the phenotype is severe because every long-chain fatty acid is blocked.
Same biomarker as CPT2, different prognosis. Both CACT and CPT2 elevate C16, C18, and C18:1, but CACT is almost uniformly lethal in the neonatal period whereas CPT2 has a spectrum.