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Alpers syndrome with mitochondrial DNA depletion
Author(s) -
Rahman S.,
Taanman J.W.,
Harding B. N.
Publication year - 2002
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.2002.39286_32.x
Subject(s) - mitochondrial dna , skeletal muscle , biology , neuropathology , pathology , genetics , medicine , disease , endocrinology , gene
Background and aim: Alpers syndrome or progressive neuronal degeneration of childhood with liver disease is a rare and probably heterogeneous familial disorder of unknown aetiology. We investigated mitochondrial DNA (mtDNA) levels in three cases with Alpers syndrome. Methods: Three unrelated patients presented with status epilepticus and liver dysfunction between 6 months and 3 years of age. The clinical course was severely progressive and death occurred 7 days to 2 years after initial presentation. Neuropathology was performed in cases 1 and 3 and confirmed a diagnosis of Alpers syndrome. Total genomic DNA extracted from frozen skeletal muscle, liver, heart and kidney was subjected to quantitative Southern blot analysis using two probes (one for mtDNA and the other for the nuclear‐encoded 18S ribosomal DNA) and comparison with age‐matched controls. Results: Case 1 had 25% residual mtDNA levels in liver, 33% in skeletal muscle, 55% in cardiac muscle and normal levels in kidney. Case 2 had 19% residual mtDNA levels in liver and 42% in skeletal muscle. Case 3 had normal mtDNA levels in skeletal muscle, the only tissue available for study. Discussion: We conclude that Alpers syndrome may be associated with depleted levels of mtDNA. The underlying genetic defect is likely to involve mtDNA maintenance. Quantitative determination of residual mtDNA levels should be performed in all cases where there is a suspicion of Alpers syndrome.