TY - JOUR
T1 - Infantile encephalopathy associated with the MELAS A3243G mutation
AU - Sue, Carolyn M.
AU - Bruno, Claudio
AU - Andreu, Antonio L.
AU - Cargan, Abba
AU - Mendell, Jerry R.
AU - Tsao, Chang Yong
AU - Luquette, Mark
AU - Paolicchi, Juliann
AU - Shanske, Sara
AU - DiMauro, Salvatore
AU - De Vivo, Darryl C.
PY - 1999
Y1 - 1999
N2 - MELAS syndrome is typically characterized by normal early development and childhood-onset recurrent neurologic deficits (stroke-like episodes), seizures, short stature, lactic acidosis, and ragged red fibers on muscle biopsy specimens. It is usually, but not invariably, associated with the A3243G point mutation in the mitochondrial DNA tRNA(Leu(UUR)) gene. We report 3 unrelated children with the A3243G mutation who presented with severe psychomotor delay in early infancy. One patient's clinical picture was more consistent with Leigh syndrome, with apneic episodes, ataxia, and bilateral striatal lesions on brain magnetic resonance imaging (MRI). The second patient had generalized seizures refractory to treatment and bilateral occipital lesions on brain MRI. The third child had atypical retinal pigmentary changes, seizures, areflexia, and cerebral atrophy on brain MRI. All patients had several atypical features in addition to early onset: absence of an acute or focal neurologic deficit, variable serum and cerebrospinal fluid lactate levels, lack of ragged red fibers in muscle biopsy specimens. The proportion of mutant mtDNA in available tissues was relatively low (range, 5% to 51% in muscle; 4% to 39% in blood). These observations further extend the phenotypic expression of the A3243G 'MELAS' mutation. Our findings confirm previous observations that there is poor correlation between abundance of mutant mtDNA in peripheral tissues and neurologic phenotype. This suggests that other factors contribute to the phenotypic expression of this mutation.
AB - MELAS syndrome is typically characterized by normal early development and childhood-onset recurrent neurologic deficits (stroke-like episodes), seizures, short stature, lactic acidosis, and ragged red fibers on muscle biopsy specimens. It is usually, but not invariably, associated with the A3243G point mutation in the mitochondrial DNA tRNA(Leu(UUR)) gene. We report 3 unrelated children with the A3243G mutation who presented with severe psychomotor delay in early infancy. One patient's clinical picture was more consistent with Leigh syndrome, with apneic episodes, ataxia, and bilateral striatal lesions on brain magnetic resonance imaging (MRI). The second patient had generalized seizures refractory to treatment and bilateral occipital lesions on brain MRI. The third child had atypical retinal pigmentary changes, seizures, areflexia, and cerebral atrophy on brain MRI. All patients had several atypical features in addition to early onset: absence of an acute or focal neurologic deficit, variable serum and cerebrospinal fluid lactate levels, lack of ragged red fibers in muscle biopsy specimens. The proportion of mutant mtDNA in available tissues was relatively low (range, 5% to 51% in muscle; 4% to 39% in blood). These observations further extend the phenotypic expression of the A3243G 'MELAS' mutation. Our findings confirm previous observations that there is poor correlation between abundance of mutant mtDNA in peripheral tissues and neurologic phenotype. This suggests that other factors contribute to the phenotypic expression of this mutation.
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U2 - 10.1016/S0022-3476(99)70283-0
DO - 10.1016/S0022-3476(99)70283-0
M3 - Article
C2 - 10356136
AN - SCOPUS:0033498227
SN - 0022-3476
VL - 134
SP - 696
EP - 700
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 6
ER -