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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nutritional approaches are available for the management of several different classes of inborn metabolism errors. In phenylketonuria (PKU), phenylalanine is not properly metabolized; and its accumulation leads to neurologic dysfunction and metal retardation. Altering the diet to limit phenylalanine intake led to remarkable improvement in children with PKU. It was later found that instituting dietary therapy immediately after identification of the disorder in newborns prevented mental retardation. Throughout the 1960s nutritional therapies were found for other inborn disorders, including galactosemia, maple syrup urine disease, and homocystinuria. For the group of disorders associated with defects in the urea cycle, leading to profound hyperammonemia, therapy based on the concept of waste nitrogen excretion (i.e., by increasing excretion of urea cycle intermediates in the urine, nitrogen that would otherwise recycle as ammonia can be eliminated) dramatically produced better control of hyperammonemia and its consequences. Some inborn errors of metabolism respond to vitamin therapy. Biotin-related multiple carboxylase synthetase deficiency can be produced by either of two enzyme defects--holocarboxylase synthetase deficiency or biotinidase deficiency. Both are treatable with biotin supplementation. The symptoms of multiple carboxylase deficiency can also occur after intestinal resection or ingestion of raw eggs. Multiple carboxylase deficiency has been treated successfully in utero by giving the mother biotin supplements. Peroxisomal disorders may respond to dietary management. Liver disease in hereditary tyrosinemia may be accentuated by hypermethioninemia and treated by controlling the blood methionine level. Glycogen storage disease Type I, which causes hypoglycemia, can be controlled by oral administration of cornstarch.
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PMID:Nutritional therapy for selected inborn errors of metabolism. 268 28

A 3-year-old girl, her mother, and maternal uncle had microcephaly and mental retardation. Their facial appearance is characterized by deep-set eyes, short philtrums, and a "beaked" nose. The mother and uncle live in an adult foster care facility because of mental retardation. The 3-year-old girl has a developmental quotient of 55. Mother has normal phenylalanine level and the child's chromosomes are normal. This appears to be a first report of a autosomal dominant form of microcephaly associated with mild to moderate mental retardation in contrast to absent or mild mental retardation described in earlier reports.
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PMID:Autosomal dominant microcephaly with mental retardation. 280 73

The low-calorie sweetening agent, aspartame, is broken down in the small intestine into three moieties: aspartic acid, methanol and phenylalanine. Acute loading studies have been performed in human beings who received up to six times the 99th percentile of the projected daily intake (6 X 34 = 200 mg/kg). No evidence of risk to the fetus was developed. Aspartate does not readily cross the placenta. Small elevations of blood methanol following such abuse doses of aspartame did not lead to measurable increases of blood formic acid, which is the product responsible for the acidosis and ocular toxicity in methanol poisoning. Phenylalanine is concentrated on the fetal side of the placenta. Aspartame in abuse doses up to 200 mg/kg in normal subjects, or to 100 mg/kg in PKU heterozygotes, did not raise blood phenylalanine levels to the range generally accepted to be associated with mental retardation in the offspring. It is concluded that, under foreseeable conditions of use, aspartame poses no risk for use in pregnancy.
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PMID:Use of aspartame in pregnancy. 286 25

We gave folinic acid to three siblings, and to a fourth child, who have or had dihydropteridine reductase (DHPR) deficiency. The youngest began folinic acid therapy in addition to neurotransmitter precursors and a phenylalanine-restricted diet at age 2 months, and at 2 years of age has near normal development without evidence of neurologic impairment. His older brother began similar treatment at 5 1/2 months of age, when early neurologic findings were evident. At age 6 years his mental retardation and neurologic impairment are less severe than reported in most patients with DHPR deficiency. Little improvement occurred in their sister, who first received treatment at 2 years of age, when she already had severe neurologic impairment. An unrelated boy with profound neurologic impairment showed subtle signs of improvement after he began treatment with folinic acid alone at age 9 years. These results provide evidence that folinic acid is important in the treatment of DHPR deficiency and, if begun early in infancy, may prevent irreversible neurologic damage. The mechanism of folinic acid action in DHPR deficiency may be to increase indirectly the synthesis of 5-methyltetrahydrofolate.
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PMID:Folinic acid therapy in treatment of dihydropteridine reductase deficiency. 287 84

Pregnant rats were loaded with L-phenylalanine, and the distributions of [14C]leucine and [14C]urea into fetal plasma and tissues were examined. Uptake of [14C]leucine into the supernatant and protein fractions of fetal plasma and tissues was low in the rats loaded with phenylalanine. In contrast, [14C]urea was distributed identically in both groups, indicating that maternal hyperphenylalaninemia did not affect blood flow across the placenta. Administration of phenylalanine and p-chlorophenylalanine produced amino acid imbalance in fetal tissues. Along with these changes, polysomes of the affected fetal heart and brain disaggregated without changes in the ribonuclease activity. These results indicate that high phenylalanine levels in maternal plasma disturb the active transport of amino acids across the placenta, causing an amino acid imbalance and disaggregation of polysomes in fetal heart and brain. These changes may contribute to the congenital heart disease and mental retardation of maternal phenylketonuria.
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PMID:Effects of phenylalanine loading on protein synthesis in the fetal heart and brain of rat: an experimental approach to maternal phenylketonuria. 294 18

Two sibs with palmo-plantar keratosis and dendritic corneal opacities, previously described as suffering from Richner-Hanhart syndrome by other authors, about 25 years ago, showed increased plasma and urine tyrosine levels. Their neurological and mental features were within normal limits. A comprehensive review of the literature showed a total of 47 cases of fully documented tyrosinemia type II; 8 more patients also had the clinical features of the disease, but aminoacidemia had never been observed. The importance of early diagnosis is stressed, since a low tyrosine-phenylalanine diet dramatically improves the symptoms and may prevent mental retardation.
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PMID:Tyrosinemia type II in two cases previously reported as Richner-Hanhart syndrome. 294 25

Maternal hyperphenylalaninemia (HPH) due to deficient phenylalanine (Phe) hydroxylation is a recognized human teratogen associated with an increased incidence of intrauterine growth retardation, microcephaly, congenital heart disease, and mental retardation. There are no previous reports of experimental HPH during organogenesis. Sustained HPH was produced in pregnant guinea pigs by adding 3.5% Phe and 1.0% parachlorophenylalanine (pCPA), an inhibitor of Phe hydroxylase, to standard guinea pig chow. Animals consumed the supplemented test diets from gestation day 1 until killed on gestation day 17. Examination of day 17 embryos revealed that embryonic mortality was associated only with maternal pCPA administration and was independent of the degree of maternal HPH. Embryonic malformation was associated with maternal HPH as well as maternal pCPA administration. Both maternal HPH and pCPA administration were associated with embryonic growth retardation. There was no association between maternal food intake or plasma tyrosine levels and embryonic abnormality or mortality. Both Phe and tyrosine were found to be concentrated in gestation day 17 yolk sac fluid when compared to maternal plasma Phe and tyrosine. The association of embryonic malformation and maternal HPH is consistent with human data. The embryotoxicity of pCPA requires further study and highlights the necessity of appropriate controls in models of experimental HPH.
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PMID:Experimental hyperphenylalaninemia in the pregnant guinea pig: possible phenylalanine teratogenesis and p-chlorophenylalanine embryotoxicity. 296 29

We have recently shown that cytoplasmic malate dehydrogenase (MDH-s) from several non-human species catalyses the reduction of aromatic alpha-keto acids in the presence of NADH (Friedrich et al. 1987), an activity previously attributed to the enzyme aromatic alpha-keto acid reductase (KAR E.C.1.1.1.96). Here we present evidence that this also occurs in humans, and that the previously characterized human KAR is not the product of a genetically distinct locus. Human MDH-s and KAR activities co-migrate after starch gel electrophoresis, and electrophoretic variants of human MDH-s exhibited identical variation for KAR. Both enzymes show almost no electrophoretic variation among human populations of diverse origin. The reduction of aromatic alpha-keto acids is substantially inhibited by malate, the end-product of the MDH reaction. Antibodies raised against purified chicken MDH-s equally inhibited both MDH-s and KAR in chickens and humans. The bulk of the KAR activity in human blood appears to be due to MDH-s, with a minor fraction catalysed by LDH, as is the case in most other species studied. The previous assignment of a gene for KAR to human chromosome 12 in human/Chinese hamster somatic cell hybrids is questioned because interspecific hybrid bands of both MDH-s and LDH appear with slightly different mobility approximately midway between the human and hamster controls in somatic cell hybrid studies, and the meaning of this artifact is discussed. The discovery that MDH reacts with intermediate metabolites of phenylalanine and tyrosine has implications in relation to the mechanism by which mental retardation may be produced in phenylketonuria (PKU), and the effect of MDH inhibition on oxidative phosphorylation in the various tyrosinaemias is discussed.
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PMID:Biochemical and genetic identity of alpha-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes. 305 44

Pregnant women with untreated phenylketonuria (PKU) with blood phenylalanine levels greater than 1200 mumol/L usually give birth to offspring with congenital birth defects, including microcephaly, cardiac defects and mental retardation. According to Mabry and Levy, hyperphenylalaninaemic (HPA) women with blood phenylalanine levels between 600 and 1200 mumol/L also have an increased risk to their offspring. To study this problem further, the National Institute of Child Health and Human Development has established a collaborative study for 7 years to elucidate a proper treatment programme for these women.
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PMID:Maternal phenylketonuria. 309 85

The literature on maternal phenylketonuria (MPKU) is reviewed in terms of its identification, description, and treatment. A number of professionals have projected a rebound in the frequency of mental retardation associated with PKU since the discovery of MPKU. The lack of knowledge of the exact causal mechanism of the phenomenon and the absence of a consistently effective treatment are emphasized. Evidence gathered regarding the effectiveness of the low phenylalanine diet in the prevention of MPKU is presented, and the implications of this evidence are discussed. Issues surrounding both the phenomenon and possible preventive measures are also discussed. Finally, some questions and responsibilities to be considered by physicians, mental retardation professionals, and policy makers are presented.
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PMID:Maternal phenylketonuria: cause for concern among women with PKU. 331 Jan 39


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