Maradin, Miljenka and Fumić, Ksenija and Hansikova, H. and Tesarova, M. and Wenchich, L. and Dorner, Sanja and Sarnavka, Vladimir and Zeman, J. and Barić, Ivo
Fumaric aciduria: Mild phenotype in a 8-year-old girl with novel mutations.
Journal of Inherited Metabolic Disease, 29 (5).
ISSN 0141-8955 (Print) 1573-2665 (Electronic)
Fumaric aciduria is a rare, autosomal recessive disorder caused by deficient acitivity of fumarate hydratase (FH). Common clinical features are hypotonia, failure to thrive, severe psychomotor retardation and seizures. Facial dysmorphism and brain malformations are frequent. Recently, some FH gene mutations have been associated with inherited cutaneous and uterine leiomyomas and papillary renal cell cancer. Our patient had a relatively mild phenotype, previously not reported genotype and familiar tumor predisposition. Mother and grandmother had uterine myomas. Paternal grandfather and his two brothers died from lung and laryngeal cancers. The pregnancy was complicated by bleeding and intrauterine growth retardation. Delivery was after 35 weeks, with normal Apgar score. The girl was hypotonic since birth. At age 2 months parents noticed short apnoic crises. She could sit at age 1.5 years, walk with assistance at 4 years. At age 8 years highly increased excretion of fumaric acid was found twice (217 and 445 mmol/mol creatinine). Shortly before that the girl started to have leg and arm spasms. Grand mal seizures ocurred twice. Facial dysmorphism included depressed nasal bridge, anteverted ears, hypertelorism and microcephaly. Speech was limited to few disyllables. She was atactic with spastic paraparesis. Brain MRI showed slight ventriculomegaly, white matter atrophy and hypoplasia of corpus callosum. Activity of FH in fibroblasts was 1.9 nmol/min/mg protein (controls 40-80). FH gene analysis revealed the maternally derived c. 1029_1031delAGT mutation, resulting in Val deletion and substitution of Gln into His, and paternally derived c. 976C>T mutation, resulting in substitution of Pro into Ser.
||Mutation ; Fumarate Hydratase - deficiency - genetics ; Metabolism, Inborn Errors - diagnosis - genetics - pathology ; Brain - pathology ; Child ; Family Health ; Female ; Humans ; Magnetic Resonance Imaging ; Phenotype
||Katedra za pedijatriju
||07 Dec 2006
||23 Sep 2011 16:09
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