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)

We describe a child with ATR-16 [alpha-thalassemia (thal)/mental retardation], who was referred for genetic evaluation because of minor anomalies and developmental delay. Cytogenetic analysis demonstrated a de novo complex rearrangement of chromosome 16. Fluorescence in situ hybridization (FISH) analysis, using chromosome 16 subtelomeric probes, showed that this patient had a deletion of the distal short arm of chromosome 16 that contains the alpha-globin genes and a duplication of 16q. Analysis of the alpha-globin locus by Southern blot showed a half normal dose of the alpha-globin gene. Microsatellite marker studies revealed that the duplicated 16q region was maternal in origin. Hematological studies revealed anemia, hypochromia and occasional cells with Hb H inclusion bodies. A hematological screening for alpha-thal should be considered in patients with mild developmental delay and a suggestive phenotype of ATR-16 with microcytic hypochromic anemia and normal iron status. The stellate pattern of the iris, a new finding in our patient, may contribute to a better clinical delineation of both syndromes, ATR-16 and/or duplication of 16qter.
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PMID:ATR-16 due to a de novo complex rearrangement of chromosome 16. 1592 Nov 66

Iron deficiency is a continuum beginning from lowering of tissue stores to the phase of exhausted tissue stores, interference with iron driven biochemical reactions in the body, microcytosis, hypochromia, increasing severity of anaemia with all its attendant consequences. Iron deficiency anaemia is a very well known concept but what is often not appreciated is the effect of broad canvas of iron deficiency on various tissues, organs and systems in our body in addition to iron deficiency anaemia leading to concept of "Iron deficiency disease". In this condition not only tissue delivery of oxygen is compromised but proliferation, growth, differentiation, myelinogenesis, immunofunction, energy metabolism, absorption and biotransformation are compromised leading to abnormal growth and behaviour, mental retardation, reduced cardiac performance and work efficiency, infection etc which ultimately leads to the concept that "iron deficiency not only breaks the machine but also wrecks the machinery."
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PMID:Non haematological effects of iron deficiency - a perspective. 1644 88

The present study was undertaken to evaluate the nutritional status of children with special needs in Alexandria city, on the basis of nutrient intake and food consumption. Socio-demographic characteristics and dietary data were determined in a sample of 231 disabled children chosen randomly from five specialized day care centers. Results showed that the age of the sample ranged from less than 7 to 24 years with a mean age of 12.6 +/- 4.7 years. Mental retardation represents the highest proportion of subjects followed by Down's syndrome and then Autism Male subjects were found to consume higher nutrients than females at all ages except age under seven years. The intake of both gender was less than the recommended for energy, calcium, vitamin A, niacin and zinc. While the intake of protein and vitamin C was more than the RDA Iron intake was below the recommended for females at all ages and within the acceptable level for male. The results also showed that there is a relationship between nutrient intake and disability type. Down syndrome children were found to consume more nutrients than mentally retarded and autistic subjects.
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PMID:Assessment of the nutritional status of children with special needs in Alexandria: I. Nutrient intake and food consumption. 1691 48

Mutations in the pantothenate kinase 2 gene (PANK2) are the cause of pantothenate kinase associated neurodegeneration (PKAN), an autosomal recessive (AR) disorder characterized by motor symptoms as such as dystonia or parkinsonism, mental retardation, retinitis pigmentosa and iron accumulation in the brain. As many neurodegenerative conditions have similar clinical features we screened a number of adult and childhood onset movement disorders for PANK2 mutation. This included cases with neurodegeneration and brain iron accumulation, corticobasal degeneartion, progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atropy, giant axonal neuropathy (GAN), neuroaxonal dystrophy (NAD), Guam dementia and HARP syndrome (pallido-pyramidal syndrome and hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration). From our series of patients one patient with PKAN and a progressive severe dystonic syndrome, cerebellar ataxia, retinitis pigmentosa and eventual anarthria had a novel combination of two compound heterozygote mutations identified in the PANK2 gene, G-->A transition at base 1238 (G411R) and a C-->A transition at base 1184 (A395E). In the patient with HARP syndrome two compound heterozygote mutations (Met327Thr and IVS5-1 G to T) in the PANK2 gene were found. No other mutations were found in any of the other patient groups, suggesting that PANK2 mutations are not associated with the aetiology of these adult degenerative conditions and confirms the genetic heterogeneity in neurodegeneration with brain iron accumulation.
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PMID:PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease. 1696 35

Internationally recognized research findings on the potential health benefits of preventing micronutrient deficiencies--especially reduced child mortality from vitamin A deficiency and prevention of in utero developmental damage and mental retardation from iodine deficiency--have contributed to raising the awareness of deficiencies and the commitment of many governments to their reduction or near-elimination. The procedures undertaken to decide on large-scale programs followed conventional patterns in the 12 countries included in this study (11 Asian countries plus South Africa). Thus, a sequence of national surveys, institutional arrangements through intersectoral technical committees, legislation, incorporation of programs into national plans, and resource mobilization, including external assistance, was similar for all three micronutrients. Vitamin A supplementation twice yearly to children, then to women postpartum, has reached the national level. Iodized salt is universally adopted at the national level in most countries, with a need for continuing efforts to reach underserved populations and to implement legislation and quality control. Iron programs, usually aiming at daily supplementation during pregnancy, have been pursued, but with less intensity. However, it is clear that these procedures have succeeded in creating a rapid expansion of large-scale deficiency-control programs, which while evolving are generally being maintained.
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PMID:Lessons from successful micronutrient programs. Part I: program initiation. 1801 66

TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients have motor impairment, mental retardation, retinal degeneration and iron-deficiency anaemia. Because aberrant iron metabolism may cause neural and retinal degeneration, it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes after iron uptake by endocytosis of Fe(3+)-bound transferrin receptors, or after lysosomal degradation of ferritin-iron complexes and autophagic ingestion of iron-containing macromolecules, is the chief source of cellular iron. The divalent metal transporter protein DMT1 (also known as SLC11A2) is the only endosomal Fe(2+) transporter known at present and it is highly expressed in erythroid precursors. Genetic studies, however, suggest the existence of a DMT1-independent endosomal and lysosomal Fe(2+) transport protein. By measuring radiolabelled iron uptake, by monitoring the levels of cytosolic and intralysosomal iron and by directly patch-clamping the late endosomal and lysosomal membrane, here we show that TRPML1 functions as a Fe(2+) permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair the ability of TRPML1 to permeate Fe(2+) at varying degrees, which correlate well with the disease severity. A comparison of TRPML1(-/- )ML4 and control human skin fibroblasts showed a reduction in cytosolic Fe(2+) levels, an increase in intralysosomal Fe(2+) levels and an accumulation of lipofuscin-like molecules in TRPML1(-/-) cells. We propose that TRPML1 mediates a mechanism by which Fe(2+) is released from late endosomes and lysosomes. Our results indicate that impaired iron transport may contribute to both haematological and degenerative symptoms of ML4 patients.
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PMID:The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. 1879 1

Rett syndrome (RS), a progressive severe neurodevelopmental disorder mainly caused by de novo mutations in the X-chromosomal MeCP2 gene encoding the transcriptional regulator methyl-CpG-binding protein 2, is a leading cause of mental retardation with autistic features in females. However, its pathogenesis remains incompletely understood, and no effective therapy is available to date. We hypothesized that a systemic oxidative stress may play a key role in the pathogenesis of classic RS. Patients with classic RS (n=59) and control subjects (n=43) were evaluated. Oxidative stress markers included intraerythrocyte non-protein-bound iron (NPBI; i.e., free iron), plasma NPBI, F2-isoprostanes (F2-IsoPs, as free, esterified, and total forms), and protein carbonyls. Lung ventilation/perfusion (V/Q) ratio was assessed using a portable gas analyzer, and RS clinical severity was evaluated using standard scales. Significantly increased intraerythrocyte NPBI (2.73-fold), plasma NPBI (x 6.0), free F(2)-IsoP (x1.85), esterified F2-IsoP (x 1.69), total F2-IsoP (x 1.66), and protein carbonyl (x 4.76) concentrations were evident in RS subjects and associated with reduced (-10.53%) arterial oxygen levels compared to controls. Biochemical evidence of oxidative stress was related to clinical phenotype severity and lower peripheral and arterial oxygen levels. Pulmonary V/Q mismatch was found in the majority of the RS population. These data identify hypoxia-induced oxidative stress as a key factor in the pathogenesis of classic RS and suggest new therapeutic approaches based on oxidative stress modulation.
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PMID:Systemic oxidative stress in classic Rett syndrome. 1946 63

Mutations of human PHF8 cluster within its JmjC encoding exons and are linked to mental retardation (MR) and a cleft lip/palate phenotype. Sequence comparisons, employing structural insights, suggest that PHF8 contains the double stranded beta-helix fold and ferrous iron binding residues that are present in 2-oxoglutarate-dependent oxygenases. We report that recombinant PHF8 is an Fe(II) and 2-oxoglutarate-dependent N(epsilon)-methyl lysine demethylase, which acts on histone substrates. PHF8 is selective in vitro for N(epsilon)-di- and mono-methylated lysine residues and does not accept trimethyl substrates. Clinically observed mutations to the PHF8 gene cluster in exons encoding for the double stranded beta-helix fold and will therefore disrupt catalytic activity. The PHF8 missense mutation c.836C>T is associated with mild MR, mild dysmorphic features, and either unilateral or bilateral cleft lip and cleft palate in two male siblings. This mutant encodes a F279S variant of PHF8 that modifies a conserved hydrophobic region; assays with both peptides and intact histones reveal this variant to be catalytically inactive. The dependence of PHF8 activity on oxygen availability is interesting because the occurrence of fetal cleft lip has been demonstrated to increase with maternal hypoxia in mouse studies. Cleft lip and other congenital anomalies are also linked indirectly to maternal hypoxia in humans, including from maternal smoking and maternal anti-hypertensive treatment. Our results will enable further studies aimed at defining the molecular links between developmental changes in histone methylation status, congenital disorders and MR.
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PMID:PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase. 1984 42

Childhood is a critical period for mental development. Iron deficiency will affect the development of nerve system and depress the learning ability, memory and cognitive function of children. There are a large number of literatures focusing on the mechanism of iron deficiency on mental retardation and the effect of iron reinforcement on iron deficient children in recent years. More attention has been paid to the prevention of iron deficiency. It has been proposed that the prevention of iron deficiency during early life of infants is more important than the reinforcement of iron in childhood. Exploring the relationship between iron deficiency and mental development is very important to improve the intelligence of children and the quality of whole population.
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PMID:[Advances on the study of iron deficiency and mental development in children]. 2244 73

About three-fourths of the total world population live in the tropics but consume only 6% of worldwide food production and contribute 15% of the world's net revenue explaining the short life expectancy, high infantile mortality, and poor daily caloric intake; moreover, lack of clean drinking water and deficient sanitation promote water-borne infections, diarrhea, and risk of malabsorption that contribute to the prevalence of malnutrition in the tropics. One-third of the world's population consumes insufficient iodine increasing the risk for mental retardation and deafness due to maternal hypothyroidism. The main nutritional syndromes comprise protein-energy malnutrition (marasmus and kwashiorkor); nutritional neuropathies, myelopathies and neuromyelopathies, as well as specific deficiencies of vitamins and micronutrients including iodine, iron, zinc, and selenium.
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PMID:Nutritional disorders in tropical neurology. 2382 26


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