Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumaric aciduria (fumaric acidemia, fumarase deficiency) is a rare inborn error of metabolism caused by deficient activity of fumarate hydratase, one of the constituent enzymes of the Krebs tricarboxylic acid cycle. We describe the clinical and imaging features of this disease arising from a consanguineous pedigree in 8 patients in the southwestern United States. Thirteen patients have been previously described in the medical literature. Our patients presented with an early infantile encephalopathy with profound developmental retardation and hypotonia, and most experienced seizures. Previously unreported characteristics described here include structural brain malformations, dysmorphic facial features, and neonatal polycythemia. Magnetic resonance imaging showed multiple abnormalities, including diffuse polymicrogyria, decreased cerebral white matter, large ventricles, and open opercula. Fumaric aciduria should be included in the differential diagnosis of inborn errors of metabolism that cause cerebral malformations and dysmorphic features. The possibility that inborn errors of energy metabolism may cause structural malformations deserves increased recognition.
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PMID:Fumaric aciduria: clinical and imaging features. 1080 28

Fumaric aciduria is a rare, autosomal recessive disorder caused by deficient activity 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, a previously not reported genotype and familial tumour predisposition. The mother and grandmother had uterine myomas. The 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 the parents noticed short apnoeic crises. She could sit at age 1.5 years, and 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 occurred 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). Analysis of the FH gene revealed the maternally derived c.1029_1031delAGT mutation, resulting in Val deletion and substitution of Gln by His, and paternally derived c.976C > T mutation, resulting in substitution of Pro by Ser.
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PMID:Fumaric aciduria: mild phenotype in a 8-year-old girl with novel mutations. 1697 75

Fumaric aciduria is a rare metabolic disease, with 40 cases reported so far. Fumarase deficiency leads mainly to brain abnormalities, developmental delay, and great accumulation of fumaric acid in urine. This work presents the first case of fumaric aciduria described in Brazil, which presented with some interesting clinical and biochemical findings such as colpocephaly, hepatic alterations, and marked metabolic acidosis since birth. Common findings were ventriculomegaly, hypotonia, and microcephaly. Biochemically, besides the high urinary fumaric acid excretion, atypical elevation of plasma citrulline, tyrosine and methionine levels were also observed. In order to show all features and variants of fumaric aciduria, literature data of 40 patients was reviewed and compared with the case reported here. Findings in all these patients demonstrate that this disorder does not yet have its phenotype completely defined; it is important that more patients be described.
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PMID:Fumaric aciduria: an overview and the first Brazilian case report. 2054 62

Fumarase deficiency is a very rare inborn error of metabolism caused by decreased activity of fumarate hydratase enzyme. We describe a fumarase-deficient infant who presented with encephalopathy, metabolic crisis, psychomotor retardation, hypotonia, seizures, and facial dysmorphism. To our knowledge, this is the first Indian child to be described with fumarase deficiency.
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PMID:Infantile metabolic encephalopathy due to fumarase deficiency. 2277 60

Fumaric aciduria is a rare autosomal recessive metabolic disease which is characterized with excessive fumaric acid exretion in urine. In the prenatal period, polyhydramniosis, intrauterine growth retardation, enlarged brain ventricles and brain anomalies are observed. Growth and development failure, hypotonia, seizures and brain atrophy are the common characteristics of patients with fumarase deficiency. On cranial imaging, the most common findings include polymicrogyria and ventriculomegaly. In our country where consanguineous marriages are common, the incidences of autosomal recessive diseases are expected to be high. In a patient who was born from a consanguineous marriage and referred to our hospital at the age of 45 days because of hyperamonemia and opistotonus, a diagnosis of fumaric aciduria was made with organic acid analysis performed considering metabolic diseases and this diagnosis was supported with radiological investigations. We thought this case was worth presenting, since there was no case of fumaric aciduria reported before in our country.
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PMID:A rare cause of opistotonus; fumaric aciduria: The first case presentation in Turkey. 2607 36

Fumarase deficiency (FD) is a rare and severe autosomal disorder, caused by inactivity of the enzyme fumarase, due to biallelic mutations of the fumarase hydratase (FH) gene. Several pathogenic mutations have been published. The article describes an infant with failure to thrive, microcephaly, axial hypotonia, and developmental retardation with increased excretion of fumarate, no activity of fumarase and a homozygous mutation of the FH gene, which was until recently only known as a variant of unknown significance. Carriers of pathogenic mutations in the FH gene are at risk for developing renal cell carcinoma and should therefore be screened. Both parents were healthy carriers of the mutation and had decreased levels of enzyme activity. In addition, the article presents an overview and analysis of all cases of FD reported thus far in the literature.
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PMID:Fumarase Deficiency: A Case With a New Pathogenic Mutation and a Review of the Literature. 3305 56