TY - JOUR
T1 - Late-onset MNGIE without peripheral neuropathy due to incomplete loss of thymidine phosphorylase activity
AU - Massa, Roberto
AU - Tessa, Alessandra
AU - Margollicci, Maria
AU - Micheli, Vanna
AU - Romigi, Andrea
AU - Tozzi, Giulia
AU - Terracciano, Chiara
AU - Piemonte, Fiorella
AU - Bernardi, Giorgio
AU - Santorelli, Filippo M.
PY - 2009/12
Y1 - 2009/12
N2 - Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE) is an autosomal recessive disorder characterized by severe gastrointestinal dysmotility, cachexia, peripheral neuropathy, ptosis, ophthalmoplegia, and leukoencephalopathy with early onset and severe prognosis. Mutations in the TYMP/ECGF1 gene cause a loss of thymidine phosphorylase catalytic activity, disrupting the homeostasis of intramitochondrial nucleotide pool. We report a woman with a very late onset of MNGIE, lacking peripheral neuropathy. Thymidine phosphorylase activity was markedly reduced in cultured fibroblasts, but only mildly reduced in buffy coat, where the defect is usually detected, and plasma thymidine was mildly increased compared to typical MNGIE patients. TYMP/ECGF1 analysis detected two heterozygous mutations, including a novel missense mutation. These findings indicate that a partial loss of thymidine phosphorylase activity may induce a late-onset and incomplete MNGIE phenotype.
AB - Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE) is an autosomal recessive disorder characterized by severe gastrointestinal dysmotility, cachexia, peripheral neuropathy, ptosis, ophthalmoplegia, and leukoencephalopathy with early onset and severe prognosis. Mutations in the TYMP/ECGF1 gene cause a loss of thymidine phosphorylase catalytic activity, disrupting the homeostasis of intramitochondrial nucleotide pool. We report a woman with a very late onset of MNGIE, lacking peripheral neuropathy. Thymidine phosphorylase activity was markedly reduced in cultured fibroblasts, but only mildly reduced in buffy coat, where the defect is usually detected, and plasma thymidine was mildly increased compared to typical MNGIE patients. TYMP/ECGF1 analysis detected two heterozygous mutations, including a novel missense mutation. These findings indicate that a partial loss of thymidine phosphorylase activity may induce a late-onset and incomplete MNGIE phenotype.
KW - Late-onset
KW - Mitochondrial disease
KW - MNGIE
KW - Peripheral neuropathy
KW - Thymidine phosphorylase
KW - TYMP/ECGF1 mutations
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U2 - 10.1016/j.nmd.2009.08.013
DO - 10.1016/j.nmd.2009.08.013
M3 - Article
C2 - 19853446
AN - SCOPUS:70449533675
VL - 19
SP - 837
EP - 840
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
IS - 12
ER -