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)

Hydroxyproline is a major constituent of collagen. It accumulates as the free imino acid in a rarely reported inborn error of metabolism known as hydroxyprolinemia. This metabolic disorder was initially described in association with mental retardation, but subsequent identification in clinically normal individuals has led to the supposition that it is benign. The possibility that hydroxyprolinemia might have an adverse effect on cognitive development without producing mental retardation has not been determined nor has its incidence been reported. We prospectively studied a girl with untreated hydroxyprolinemia identified by routine neonatal urine screening, the only infant found among 1 million screened, and compared her with her unaffected dizygotic twin sister. Plasma and urine hydroxyproline were increased approximately 10-fold and 100-fold, respectively, in the affected twin. Both girls have had normal growth, with the affected twin taller than her sister. On neuropsychologic testing, the affected twin was within normal limits, performing slightly better than her sister on verbal and achievement tests but less well on visual perceptual testing. It appears that hydroxyprolinemia has caused no physical or general cognitive deficits. The possibility of an effect on visual perceptual functioning, although unlikely, cannot be eliminated.
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PMID:Hydroxyprolinemia: comparison of a patient and her unaffected twin sister. 906 21

l-Proline concentration is primarily related to the balance of enzymatic activities of proline dehydrogenase [proline oxidase (POX)] and Delta-1-pyrroline-5-carboxylate (P5C) reductase. As a result, P5C plays a pivotal role in maintaining the concentration of proline in body fluids and inborn errors of P5C metabolism lead to disturbance of proline metabolism. Several inborn errors of proline metabolism have been described. Hyperprolinemia type I (HPI) is a result of a deficiency in POX. The POX gene (PRODH) is located on chromosome 22 (22q11.2) and this region is deleted in velo-cardio-facial syndrome, a congenital malformation syndrome. In addition, this gene locus is related to susceptibility to schizophrenia. The other type of hyperprolinemia is HPII. It is caused by a deficiency in P5C dehydrogenase activity. Hypoprolinemia, on the other hand, is found in the recently described deficiency of P5C synthetase. This enzyme defect leads to hyperammonemia associated with hypoornithinemia, hypocitrullinemia, and hypoargininemia other than hypoprolinemia. Hyperhydroxyprolinemia is an autosomal recessive inheritance disorder caused by the deficiency of hydroxyproline oxidase. There are no symptoms and it is believed to be a benign metabolic disorder. The deficiency of ornithine aminotransferase causes transient hyperammonemia during early infancy due to deficiency of ornithine in the urea cycle. In later life, gyrate atrophy of the retina occurs due to hyperornithinemia, a paradoxical phenomenon. Finally, prolidase deficiency is a rare autosomal recessive hereditary disease. Prolidase catalyzes hydrolysis of dipeptide or oligopeptide with a C-terminal proline or hydroxyproline and its deficiency can cause mental retardation and severe skin ulcers.
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PMID:Inborn errors of proline metabolism. 1880 17