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)

A case of juvenile manic-depressive illness associated with mental retardation is reported having been treated successfully with lithium carbonate. During four years of maintenance treatment with daily doses of 600 mgs. to 900 mgs. per day of lithium carbonate, disruptive manic behavior has been controlled and a subjective leveling out of mood has allowed that patient to develop more fully her cognitive and psychomotor capacities. There was one exascerbation of disruptive behavior during the first year of treatment that was easily controlled with haloperidol together with continued lithium carbonate maintenance treatment. No measurable adverse developmental or thyroid effects have been noted. The Shaffer acquiescence scale of the MMPI correctly predicted that the patient would be a positive responder to lithium carbonate treatment.
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PMID:Lithium carbonate in juvenile manic-depressive illness. 124 43

Although this article focuses on psychopharmacology, pharmacotherapy is only part of a comprehensive treatment program. Treatment should be individualized to the patient's condition and level of intellectual functioning (e.g., conduct disorder, mental retardation). Clinicians should be acquainted with the Food and Drug Administration's regulations and the Physician's Desk Reference's guidelines. Psychoactive agents should be prescribed judiciously under careful clinical and laboratory monitoring, especially when given on a long-term basis. Knowledge of potential short- and long-term side effects is imperative to minimize impairment (cognitive, sedation) and to maximize achievement of adaptive behaviors. Aggressiveness is a low-frequency behavior and therefore difficult to assess. Aggressiveness with an explosive affective component and rage seems to be more responsive to pharmacotherapy than aggressiveness alone. Children who present with covert conduct disorder symptoms, such as stealing and lying, might not be as responsive to psychoactive agents as the conduct disorder with explosive characteristics. The neuroleptics are considered the standard drugs for the treatment of aggression but sedation and concern over tardive dyskinesia have led investigators to explore and study other classes of drugs. Lithium carbonate has been studied in short-term clinical trials and has been shown to be an effective alternative to the neuroleptics. Carbamazepine and propranolol seem to be promising agents but require further critical assessment in children and adolescents. Stimulants should be considered the first choice of treatment in coexisting conduct disorder and ADHD or in milder forms of aggression. In conclusion, there is a need for systematic investigation of the effectiveness and safety of psychoactive agents in children and adolescents with aggressiveness, explosiveness, and rage outbursts. There is some supportive evidence that some patients with these target symptoms are good responders to certain drugs. Future research should compare pharmacotherapy to psychosocial treatment and the combination of both.
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PMID:The pharmacologic treatment of conduct disorders and rage outbursts. 154 49

Twenty-five published reports were reviewed regarding the occurrence of affective illness, ie, depression and mania, in mentally retarded individuals, using the DSM-III criteria to assess the validity of both diagnoses. Individuals with mental retardation (MR) were found to manifest the full range of affective disorders. Developmentally impaired social functioning and intelligence influence the clinical presentation, but not the development, of affective symptomatology. Affective disorder diagnoses can be made for patients with all levels of MR severity. In individuals with MR of mild and moderate severity, the diagnosis can be made using standard DSM-III criteria. For those with severe and profound MR, a clinically useful diagnosis can be based on changes in behavior and vegetative functioning, as well as family history of affective illness. The psychiatrically symptomatic person with MR should always be evaluated for affective symptomatology and be considered as a candidate for the full range of treatments, including psychotherapy and pharmacotherapy with antidepressants as well as lithium carbonate.
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PMID:Do the mentally retarded suffer from affective illness? 684 21

Permanent isolated proximal renal tubular acidosis (pRTA) with ocular abnormalities is a systemic disease involving short stature, isolated pRTA, mental retardation, and ocular abnormalities. Kidney Na+/HCO3- cotransporter (kNBC1) cDNA from peripheral lymphocytes from a patient with permanent isolated pRTA and bilateral glaucoma was screened, and a novel homozygous mutation, namely a cytosine-to-thymine transition at nucleotide 234, which resulted in the formation of a stop codon at codon 29, was identified. This homozygous mutation, Q29X, was identified in the unique 5'-end of the kNBC1 gene (SLC4A4) of the patient. Cosegregation of this Q29X mutation with the disease and heterozygosity in the parents of the affected patient were observed. The absence of this mutation in 156 alleles from 78 Japanese individuals indicates that this mutation is directly related to the disease and is not a common DNA sequence polymorphism. This nonsense mutation predicts a truncated kNBC1 protein that lacks the 1007 amino acids of the carboxyl-terminus, and the effect on kNBC1 cotransport activity is likely to be a loss of function. In contrast, the pancreatic Na+/HCO3- cotransporter of the patient is not likely to be affected by this nonsense mutation. These results have implications for understanding the role of kNBC1 in the pathophysiologic processes of pRTA associated with ocular abnormalities and mental retardation.
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PMID:Novel nonsense mutation in the Na+/HCO3- cotransporter gene (SLC4A4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma. 1127 32

Genetic disorders of acid-base transporters involve plasmalemmal and organellar transporters of H(+), HCO3(-), and Cl(-). Autosomal-dominant and -recessive forms of distal renal tubular acidosis (dRTA) are caused by mutations in ion transporters of the acid-secreting Type A intercalated cell of the renal collecting duct. These include the AE1 Cl(-)/HCO3(-) exchanger of the basolateral membrane and at least two subunits of the apical membrane vacuolar (v)H(+)-ATPase, the V1 subunit B1 (associated with deafness) and the V0 subunit a4. Recessive proximal RTA with ocular disease arises from mutations in the electrogenic Na(+)-bicarbonate cotransporter NBC1 of the proximal tubular cell basolateral membrane. Recessive mixed proximal-distal RTA accompanied by osteopetrosis and mental retardation is associated with mutations in cytoplasmic carbonic anhydrase II. The metabolic alkalosis of congenital chloride-losing diarrhea is caused by mutations in the DRA Cl(-)/HCO3(-) exchanger of the ileocolonic apical membrane. Recessive osteopetrosis is caused by deficient osteoclast acid secretion across the ruffled border lacunar membrane, the result of mutations in the vH(+)-ATPase V0 subunit or in the CLC-7 Cl(-) channel. X-linked nephrolithiasis and engineered deficiencies in some other CLC Cl(-) channels are thought to represent defects of organellar acidification. Study of acid-base transport disease-associated mutations should enhance our understanding of protein structure-function relationships and their impact on the physiology of cell, tissue, and organism.
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PMID:Genetic diseases of acid-base transporters. 1182 92

Enhancement of memory acquisition and recall represents an important pharmacological goal in the treatment of cognitive disorders. In addition to its involvement in pH regulation, HCO3- reabsorption and CO2 expiration, carbonic anhydrase plays a crucial role in signal processing, long-term synaptic transformation and attentional gating of memory storage. Carbonic anhydrase dysfunction impairs cognition and is associated with mental retardation, Alzheimer's disease and aging. The pharmacological profile of carbonic anhydrase has been refined and specific activators have been developed. In this article, an integrated view of the involvement of carbonic anhydrase activity in synaptic plasticity and cognition will be presented, with particular focus on attentional gating of spatial learning and memory.
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PMID:Carbonic anhydrase gating of attention: memory therapy and enhancement. 1183 Feb 65

Proximal renal tubular acidosis (pRTA) results from an impairment of bicarbonate (HCO3-) reabsorption in the renal proximal tubules, characterized by a decreased HCO3- threshold. pRTA commonly occurs as a manifestation of a generalized functional defect in proximal tubules. In contrast, pRTA can occur without other functional defects in proximal tubules (isolated pRTA). Most of the isolated pRTA in children are hereditary. Recent progress in molecular biological analyses is unraveling the molecular basis of hereditary pRTA. Mutations in the kidney type Na+/HCO3- cotransporter gene (SLC4A4) cause permanent isolated proximal RTA with ocular abnormalities. Mutations in carbonic anhydrase II gene lead to osteopetrosis, RTA (pRTA, distal RTA or combined proximal and distal RTA), cerebral calcification, and mental retardation. SLC9A3, encoding the Na+/H+ exchanger, is a candidate gene for pRTA without other manifestations. These results help further understand the molecular basis of hereditary pRTA and characterize the clinical and genetic manifestations of the disorder.
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PMID:Molecular basis of proximal renal tubular acidosis. 1202 12

Untreated idiopathic congenital central hypoventilation syndrome (CCHS) is thought to cause infant death within 1-2 months. Here we present an adult patient with CCHS who survived without continuous ventilatory support, despite hypoventilation from early childhood onward. The diagnosis was confirmed at the age of 22 years, when the patient presented with hypoventilation during the night (PaCO2 60 mm Hg, PaO2 56 mm Hg, pH 7.32 HCO3- 30 mmol/l) but hyperventilation when awake (PaCO2 26 mm Hg, PaO2 81 mm Hg, pH 7.56, HCO3- 23 mmol/l). The maximal hematocrit was 77%. Despite mental retardation, noninvasive positive pressure ventilation (NPPV) could be successfully established. NPPV-supported ventilation during the night (PaCO2 36, PaO2 84 mm Hg, pH 7.47, HCO3- 25 mmol/l) reduced hematocrit values (40.6 to 36.8%) over a period of 4 years. In conclusion, long-term survival with CCHS is possible without continuous ventilatory support. Spontaneous improvement of hypoventilation during sleep throughout childhood is possible and hyperventilation during wakefulness may occur in patients with CCHS. CCHS can be managed with NPPV despite mental retardation, even over a long-term period.
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PMID:Long-term survival of a patient with congenital central hypoventilation syndrome despite the lack of continuous ventilatory support. 1503 79

In humans and terrestrial vertebrates, the kidney controls systemic pH in part by absorbing filtered bicarbonate in the proximal tubule via an electrogenic Na+/HCO3- cotransporter (NBCe1/SLC4A4). Recently, human genetics revealed that NBCe1 is the major renal contributor to this process. Homozygous point mutations in NBCe1 cause proximal renal tubular acidosis (pRTA), glaucoma, and cataracts (Igarashi, T., Inatomi, J., Sekine, T., Cha, S. H., Kanai, Y., Kunimi, M., Tsukamoto, K., Satoh, H., Shimadzu, M., Tozawa, F., Mori, T., Shiobara, M., Seki, G., and Endou, H. (1999) Nat. Genet. 23, 264-266). We have identified and functionally characterized a novel, homozygous, missense mutation (S427L) in NBCe1, also resulting in pRTA and similar eye defects without mental retardation. To understand the pathophysiology of the syndrome, we expressed wild-type (WT) NBCe1 and S427L-NBCe1 in Xenopus oocytes. Function was evaluated by measuring intracellular pH (HCO3- transport) and membrane currents using microelectrodes. HCO3- -elicited currents for S427L were approximately 10% of WT NBCe1, and CO2-induced acidification was approximately 4-fold faster. Na+ -dependent HCO3- transport (currents and acidification) was also approximately 10% of WT. Current-voltage (I-V) analysis reveals that S427L has no reversal potential in HCO3-, indicating that under physiological ion gradient conditions, NaHCO3 could not move out of cells as is needed for renal HCO3- absorption and ocular pressure homeostasis. I-V analysis without Na+ further shows that the S427L-mediated NaHCO3 efflux mode is depressed or absent. These experiments reveal that voltage- and Na+ -dependent transport by S427L-hkNBCe1 is unfavorably altered, thereby causing both insufficient HCO3- absorption by the kidney (proximal RTA) and inappropriate anterior chamber fluid transport (glaucoma).
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PMID:A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects. 1547 65

Self-mutilation is form of self-injurious behavior which is either low intensity, high frequency form seen in personality disorder and mental retardation or low frequency, highly destructive form which occurs in the context of psychosis or acute intoxications. We report a 32 yr-old male with bipolar affective disorder presenting with multiple acts of major self-mutilation during an episode of psychotic depression. At presentation he had broken upper central incisors, circular burn scar on right palm, crush injury of left index finger with avulsed nail and cut injury over glans penis. In view of his extreme self-mutilating behavior, he was administered electroconvulsive therapy on second day following which self-mutilating behavior improved after fourth ECT. After 8 ECT sessions, he was started on lithium carbonate with a serum level of 0.82 meq/L and haloperidol 15 mg/day and there was no recurrence of self-mutilating behavior during follow up after four months.
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PMID:[Electroconvulsive therapy for multiple major self-mutilations in bipolar psychotic depression]. 1856 Oct 53


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