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)

Slightly elevated serum dolichol levels have so far been demonstrated only in alcoholics. We now report two diseases with exceptionally high serum dolichol levels. They are autosomal, recessively inherited lysosomal storage diseases, aspartylglucosaminuria (AGU) and mannosidosis. In 16 patients with AGU the mean serum level of total dolichols (457 +/- 43 ng/ml) was more than two-fold when compared to healthy controls (170 +/- 4 ng/ml). In two patients with mannosidosis the levels were almost two-fold. The percentage distribution of the dolichol homologues with 18, 19 or 20 isoprene units did not differ between the patients and controls. The inclusion of an additional control group excluded the possible influence of mental retardation and imparied moving ability on the results. Elevated serum dolichols in patients with lysosomal storage diseases may reflect a disturbance in lysosomal function and serve as a diagnostic marker. The biochemical mechanisms leading to this phenomenon remain to be established.
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PMID:Elevated levels of serum dolichol in aspartylglucosaminuria. 240 87

N-linked glycosylation is the most frequent modification of secreted and membrane-bound proteins in eukaryotic cells, disruption of which is the basis of the congenital disorders of glycosylation (CDGs). We describe a new type of CDG caused by mutations in the steroid 5alpha-reductase type 3 (SRD5A3) gene. Patients have mental retardation and ophthalmologic and cerebellar defects. We found that SRD5A3 is necessary for the reduction of the alpha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked monosaccharides, and the oligosaccharide precursor used for N-glycosylation. The presence of residual dolichol in cells depleted for this enzyme suggests the existence of an unexpected alternative pathway for dolichol de novo biosynthesis. Our results thus suggest that SRD5A3 is likely to be the long-sought polyprenol reductase and reveal the genetic basis of one of the earliest steps in protein N-linked glycosylation.
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PMID:SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. 2065 62