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 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

A severely mentally and motor retarded girl with monosomy 3pter--p25 and trisomy 8q24-qter due to a familial reciprocal translocation t(3;8) (p25;q24): We report a familial translocation t(3;8) in a three generation family that includes a severely retarded 9-year-old girl with intrauterine and postnatal growth retardation, microcephaly, capillary hemangiomas of the forehead and perioral region, synophrys, ptosis, long philtrum, high arched palate, micrognathia, malformed ears, clinodactyly, hypotonia, mental and motor retardation. The pedigree was highly suggestive ofa familial rearrangement. Cytogenetics and fluorescent in situ hybridization (FISH) showed an unbalanced translocation of chromosomes 3p25 and 8q24 of maternal origin, karyotype 46,XX,der(3)t(3;8)(p25q24)mat. Using FISH the breakpoint at 8q24 was located distal of TRPS1, the gene for trichorhinophalangeal syndrome. The balanced translocation was found in the mother, maternal grandmother and prenatally diagnosed brother. Ten individuals (seven miscarriages, niece, two nephews) probably also had an unbalanced translocation. Genetic counseling was given to the family. Because of the hemizygous deletion of the VHL gene at chromosome 3p25.3, the patient is at risk for von Hippel-Lindau (VHL) syndrome, predisposing to retinal, cerebellar, spinal haemangioblastomas, renal cell carcinoma, phaeochromocytoma and pancreatic tumors. Therefore, for early detection and treatment of VHL syndrome, we performed periodic screening beginning at age 5 years. A familial translocation t(3;8) is very rare and there are no previous reports on terminal monosomy 3p (pter-->p25) and terminal trisomy 8q (q24-->qter).
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PMID:A severely mentally and motor retarded girl with monosomy 3pter-->p25 and trisomy 8q24-->qter due to a familial reciprocal translocation t(3;8)(p25;q24). 1965 Apr 9

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