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

Two autopsy cases of congenital muscular dystrophy of Fukuyama type (F-CMD) were described. The first case was diagnosed clinically and pathologically as its typical case. Neither his family history nor the history of his prenatal period were contributory. He had suffered from muscle weakness and atrophy since his birth. Serum CPK was markedly elevated. EMG and muscle biopsy proved dystrophic changes of the skeletal muscles. In addition, he manifested mental retardation and attacks of convulsion. EEG failed to elicit remarkable changes, but PEG represented ventricular dilatation. He died of respiratory insufficiency at age 12. His postmortem examination showed variegated anomalies in the nervous system. Extensive micropolygyria was present in the cerebrum and cerebellum accompanied by adhesions between the bilateral cerebral hemispheres. Assymmetry of the longitudinal fibers was pointed out in the pontine base. Anterior horn cells were atrophic and moderately depopulated. On the other hand, the second patient was an atypical F-CMD case in symptoms, signs and pathology. His grand-mothers on both father's and mother's sides wee first cousins. His three siblings showed no similar disorders. His mother developed slight gestational toxicosis in the sixth and seventh months of pregnancy. His muscle weakness, contracture of the bilateral hip-joints and clubfoot had been observed since his birth. Physical and neurological examinations at age 6 showed deformity of the skull, myopathic face, macroglossia, high-arched palate, pigeon chest, scoliosis of the thoracic spine. In addition, generalized muscular atrophy, hypotonia and areflexia were recognized. Pseudohypertrophy of the muscles was absent. Sensation was intact to all modalities. Serum CPK and LDH were moderately increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[2 autopsy cases of congenital muscular dystrophy of Fukuyama type--a typical and an atypical cases]. 652 23

We report a 48-year-old Japanese man suffering from xeroderma pigmentosum associated with mental retardation, cerebral atrophy and cerebellar ataxia. Cultured fibroblasts from an unexposed area of skin had reduced DNA repair capacity after UV irradiation, with higher sensitivity to UV than normal cells in colony-forming ability and host cell reactivation using herpes simplex virus. Genetic complementation tests by cell fusion with polyethylene glycol revealed that the patient belonged to group F. He died of bile duct cancer at the age of 50. This is the first report of an XP-F patient with neurological abnormalities.
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PMID:A case of xeroderma pigmentosum complementation group F with neurological abnormalities. 842 28

Prolidase is a cytosolic exopeptidase whose deficiency causes the development of a rare autosomal recessive disorder known as Prolidase Deficiency (PD). The main manifestations of PD are intractable ulcerations of the skin, recurrent infections and mental retardation. At this time only a hazardous and expensive chronic therapy based on blood transfusions is the suggested treatment for PD. The aim of this work was to investigate the capability of utilizing liposomes as enzyme carriers: these vesicular systems have been recently evaluated as protein carriers for their potential in terms of "in vivo" localization, drug release and for protein stabilization in biological fluids. Liposomes were prepared, with a 1:1 PC:Col molar ratio with or without DSPE-PEG, by a thin-film hydration. Ex-vivo experiments were performed, incubating prolidase loaded liposomes with cultured fibroblasts from PD patients and from controls, to determine the amount of active enzyme delivered to cells. Evaluation of liposomes toxicity on cultured skin fibroblasts showed that liposomes did not interfere with cellular growth. Results showed that all the active prolidase encapsulated in the liposomes was completely vehiculated inside fibroblasts after 6 days incubation. SEM analysis suggests that prolidase is vehiculated inside the cell through liposome endocytosis.
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PMID:Intracellular delivery of liposome-encapsulated prolidase in cultured fibroblasts from prolidase-deficient patients. 1565 44

Phenylketonuria (PKU) is a metabolic disorder due primarily to mutations in the PAH gene that impair both phenylalanine hydroxylase activity and disposal of l-phenylalanine from the normal diet. Excess phenylalanine is toxic to cognitive development and a low-phenylalanine diet prevents mental retardation, but it is a difficult therapeutic option. Previous studies with recombinant phenylalanine ammonia-lyase, PAL, demonstrated pharmacologic and physiologic proofs of principle for PAL as an alternative therapy for PKU but its immunogenicity was problematic. From a series of formulations of linear and branched polyethylene glycols chemically conjugated to PAL, we have created a parenteral therapeutic agent for PKU treatment. All the pegylated molecules were fully characterized in vitro and the most promising formulations were then tested in vivo in the PKU mouse model. The linear 20-kDa PEG-PAL combination abolished in vivo immunogenicity after repeated challenge while retaining full catabolic activity against phenylalanine, suggesting potential as a novel PKU therapeutic.
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PMID:Development of pegylated forms of recombinant Rhodosporidium toruloides phenylalanine ammonia-lyase for the treatment of classical phenylketonuria. 1592 70

Little is known about the mechanism by which ethylene glycol monomethyl ether (EGME) produces genotoxic effects in humans. The authors found that individuals exposed in utero to EGME showed characteristic dysmorphic features, unexplained mental retardation, and persistent cytogenetic damage. They hypothesized that these individuals had a higher level of terminal chromosome arrangements, accounting for the genomic instability detected. Results indicate that in utero-exposed individuals have significantly reduced telomeres relative to non-in utero-exposed participants. The M +/- SEM pixel intensity in the in utero-exposed participants was 43.6 +/- 7.6 compared with 74.1 +/- 1.9 in the non-in utero-exposed. Findings suggest that exposure to EGME in utero could result in terminal chromosome rearrangements and shortening of telomere length, leading to the observed dysmorphic features and idiopathic mental retardation.
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PMID:Reduction in telomere length in individuals exposed in utero to glycol ether. 1840 Jun 57

Propionic acidemia (PA) is a metabolic disorder that causes mental retardation and that can be fatal if untreated. PA is inherited in an autosomal recessive fashion involving mutations in PCCA or PCCB encoding the alpha and beta subunits of propionyl-CoA carboxylase (PCC). Current treatment is based on dietary restriction of substrate amino acids, which attenuates symptoms. However, patients still experience episodes of hyperammonemia that can cause progressive neurologic damage. In this paper, we have tested gene therapy approaches to PA in a stringent mouse model of PCCA deficiency, in which homozygous knockout mice are born but die within 36 hr. In this work, we have delivered first-generation and helper-dependent adenovirus serotype 5 (Ad5) vectors expressing the human PCCA cDNA by intraperitoneal injection into newborn mice. Unmodified Ad5 vectors mediated extensive transduction of the peritoneum with weak liver transduction as determined by luciferase imaging and dsRed expression. In contrast, modification of Ad5 with polyethylene glycol detargeted the virus from the peritoneum and retargeted it for transduction in the liver. When vectors expressing PCCA were injected, significant increases in life span were observed for both the unmodified and polyethylene glycol (PEG)-modified Ad5 vectors. However, this rescue was transient. Similarly, adeno-associated virus serotype 8-mediated transduction also produced only transient rescue. These data show first proof of principle for gene therapy of PA and demonstrate the potential utility of PEG to modify viral tropism in an actual gene therapy application.
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PMID:Short-term rescue of neonatal lethality in a mouse model of propionic acidemia by gene therapy. 1902 75

Alkaline phosphatase (ALP) in humans comprises a family of four cell-surface phosphomonoester phosphohydrolase isozymes. Three genes separately encode the "tissue-specific" ALPs whereas the fourth gene encodes ubiquitous homodimeric "tissue-nonspecific" ALP (TNSALP) richly expressed in bone, liver, kidney, and developing teeth. TNSALP monomers have five putative N-linked glycosylation sites where different post-translational modifications account for this isozyme's distinctive physicochemical properties in different organs. Three bone-derived TNSALP (BALP) isoforms (B/I, B1, and B2) are present in healthy serum, whereas a fourth BALP isoform (B1x) can circulate in chronic kidney disease. Herein, we report a healthy boy with persistent hyperphosphatasemia due to BALP levels two- to threefold higher than age-appropriate reference values. High-performance liquid chromatography, electrophoresis, heat inactivation, catalysis inhibition, and polyethylene glycol precipitation revealed increased serum B/I, B1, and B2 differing from patterns found in skeletal diseases. B/I was ~23-fold elevated. Absence of mental retardation and physical stigmata excluded Mabry syndrome, the ALP-anchoring disorder causing hyperphosphatasemia. Routine biochemical studies indicated intact mineral homeostasis. Serum N-terminal propeptide of type I procollagen (P1NP) level was normal, but C-terminal cross-linking telopeptide of type I collagen (CTX) level was elevated. However, radiological studies showed no evidence for a generalized skeletal disturbance. Circulating pyridoxal 5'-phosphate, a TNSALP natural substrate, was not low despite the laboratory hyperphosphatasemia, thereby suggesting BALP phosphohydrolase activity was not elevated endogenously. Mutation analysis of the ALPL gene encoding TNSALP revealed no defect. His non-consanguineous healthy parents had serum total ALP activity and BALP protein levels that were normal. Our patient's sporadic idiopathic hyperphosphatasemia could reflect altered post-translational modification together with increased expression and/or impaired degradation of BALP.
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PMID:Persistent idiopathic hyperphosphatasemia from bone alkaline phosphatase in a healthy boy. 3247 45