We describe a 3.5-year-old female with
Alpers disease with a POLG genotype of p.A467T/p.G848S and with a lethal outcome. Laboratory investigation revealed elevated CSF
neopterin,
IL-6,
IL-8, IFN-gamma, reduced CSF
5-methyltetrahydrofolate (5MTHF), and increased serum as well as CSF
folate receptor blocking
autoantibodies. Treatment with oral Leucovorine (5-formyl-tetrahydrofolate) was initiated at 0.25mg/kg bid, and later increased to 4mg/kg bid. Under treatment CSF levels of 5MTHF, seizure frequency and communicative abilities improved. Over a time span of 17months, CSF levels of
IL-6 and IFN-gamma decreased, levels of
folate receptor blocking
autoantibodies continued to raise, whereas CSF
IL-8 remained elevated 1500-fold above normal. The child died without apparent stress at the age of 5.5years.
Alpers disease, a
neurodegenerative disease usually presents in the first years of life as a progressive
encephalopathy with multifocal
myoclonic seizures, developmental regression,
cortical blindness and early death. The underlying genetic defect has been attributed to mutations of the catalytic subunit of the
mitochondrial DNA polymerase-gamma leading to an organ-specific
mitochondrial DNA depletion syndrome with reduced activity of respiratory chain
enzyme complexes in the brain and the liver. A curative
therapy is not available. This case report of
Alpers disease provides new insights into the pathophysiology of
Alpers disease, where
mitochondrial dysfunction in conjunction with inflammatory
cytokines and blocking
folate receptor
autoantibodies may lead to a secondary cerebral
folate deficiency syndrome. The treatment of the latter provides relief to the patient without stopping the underlying disease.