Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 16-year-old boy with severe congenital unconjugated hyperbilirubinaemia is described in whom mental retardation occurred as an isolated neurological deficit. The diagnosis of Crigler-Najjar type 1 syndrome was supported by an extreme and persistent elevation of serum unconjugated bilirubin (650 mumol/l), failure of administered phenobarbitone to lower serum bilirubin concentration and family history of a similarly affected sibling. Hepatic bilirubin UDP-glucuronyl transferase activity determined in vitro by a sensitive new enzyme assay was found to be absent using bilirubin or bilirubin monoglucuronide as substrate. Phototherapy for 12 hours each night produced a partial but highly significant reduction in serum bilirubin concentration, which was not influenced further by the administration of cholestyramine.
 ...
PMID:Crigler-Najjar Type 1 syndrome: absence of hepatic bilirubin UDP-glucuronyl transferase activity and therapeutic responses to light. 681 11

Leukocyte adhesion deficiency type II is an autosomal recessive syndrome characterized by generalized reduction of L-fucose in glycoconjugates; the specific molecular defect is still undefined. The most important clinical symptoms include severe growth and mental retardation and severe immunodeficiency. Patients from two ethnic groups have been reported, i.e. Arab and Turkish. We have observed that GDP-L-fucose transport into Golgi vesicles was specifically impaired in an Arab patient, with a significant reduction of the V:(max) but no significant differences in the K:(m) from control and parents. GDP-L-fucose transport showed simple saturation kinetics in all samples. Transport of UDP-galactose, UDP-N:-acetylglucosamine, and CMP-sialic acid was comparable into vesicles from the Arab patient, parents, and control. These kinetic parameters probably account for the failure to obtain any clinical and biochemical response to fucose therapy in Arab patients. This contrasts both with the distinctive kinetic properties of GDP-L-fucose transport and with the success of fucose therapy, which have been recently reported in one patient of Turkish origin. Accordingly, the biochemical properties of GDP-L-fucose transport into the Golgi are consistent with different variants of leukocyte adhesion deficiency type II that are probably the result of different molecular defects.
 ...
PMID:Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients. 1126 38

Crigler-Najjar Syndrome is an uncommon genetic disorder characterized by the elevation of unconjugated plasmatic bilirubin secondary to deficiency of the enzyme uridine diphosphate glucuronyltransferase (UDP-GT). We report a 19-years-old woman with the syndrome diagnosed during the neonatal period, when she developed a severe jaundice in the first 10 days of life, reaching unconjugated bilirubin levels of 29 mg/dl, with normal liver function tests. After transient response to phototherapy, the patient was referred to a tertiary medical center in which an extensive work up ruled out other etiologies and the diagnosis of type I Crigler-Najjar syndrome was established. Currently, the patient has a mild mental retardation. She is receiving homemade phototherapy 18 h per day with acceptable control of bilirubin levels. Many mutations have been associated with UDP-GT dysfunction resulting in a broad spectrum of the disease. When bilirubin rises above physiological limits, it permeates the hematoencephalic barrier, inducing bilirubin impregnation of basal ganglia with secondary neuronal damage and necrosis. The worst outcome, kernicterus, is characterized by mental retardation, central deafness, ophthalmoplegia, ataxia, athetosis, spasticity, seizures and death. First line therapy includes phototherapy, but definitive therapy is liver transplantation before the occurrence of neurological damage.
...
PMID:[Crigler-Najjar syndrome. Report of one case with a long term follow up]. 2486 Nov 23