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)

In Japan, mass screening tests on newborns for Cretinism have been performed since 1984, Cretinism is a very rare condition. We report the clinical course and complications of longitudinal thyroid hormone replacement therapy (liothyronine sodium: T3) of two women with Cretinism and ectopic thyroid gland for the past 33 years until 2001. They were born in April 1951 (Case 1) and in January 1952 (Case 2). On admission in June 1968, they were 17 and 16 years old. They had short stature, mental retardation, macroglossia, saddle nose, retardation of bone maturation, edematous face, coexistence of permanent teeth and deciduous teeth, abdominal distention, hypotonia, anemia, hypophosphatemia and hypercholesterolemia. After admission, Case 2 had an appendectomy for appendicitis. She was found to have a right ovarian cyst, but was not operated upon. Later, the right ovarian cyst disappeared during thyroid hormone replacement therapy. The complication in this case was NIDDM. Over secretion of thyroid hormone in for example, hyperthyroidism sometimes induces NIDDM. On their admission, a levothyroxine sodium (T4: Thyradin S) was unavailable in Japan, so we had no choice but to treat them with liothyronine sodium for thyroid hormone replacement therapy. We suspect that liothyronine sodium replacement therapy probably induced NIDDM. They experienced improved bone maturation, anemia, hypophsphatemia and hypercholesterolemia, but their intellectual and mental disabilities were not improved.
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PMID:The longitudinal course of two cases with cretinism diagnosed after adolescence. 1280 80

Hyperammonemia is a common finding in children with methylmalonic acidemia, an inherited metabolic disease characterized by mental retardation, convulsions, and accumulation of methylmalonic acid (MMA). Although it has been suggested that MMA induces convulsions through succinate dehydrogenase (SDH) inhibition, very little is known about the contribution of hyperammonemia to the development of convulsions in these patients. In the present study we investigated the effects of ammonium ions on the convulsant action of MMA, MMA-induced inhibition of striatal succinate dehydrogenase, and the striatal content of thiobarbituric acid-reactive substances (TBARS). Adult rats were injected with ammonium acetate (1.5 mmol/kg, sc) or sodium acetate (1.5 mmol/kg, sc), followed 5 min later by buffered MMA (3 micromol/microl) or NaCl (4.5 micromol/microl) injected into the striatum. The animals were observed in an open field for the appearance of convulsive episodes. After 30 min of behavioral evaluation, the animals were sacrificed and had their striatal TBARS content measured. Ammonium acetate pretreatment caused no behavioral effects per se, but potentiated MMA-induced convulsions and increased basal TBARS content and MMA-induced TBARS production in the striatum. Ammonium chloride had no effect on basal succinate dehydrogenase activity and did not alter MMA-induced inhibition of SDH in vitro. These results suggest that ammonia potentiates MMA-induced behavioral effects through a mechanism that does not involve further succinate dehydrogenase inhibition, but may involve facilitation of MMA-induced oxidative damage and provide evidence that ammonia and MMA may have mutually additive toxicity.
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PMID:Ammonia potentiates methylmalonic acid-induced convulsions and TBARS production. 1289 56

Hypokalemia is associated with some renal diseases manifested by renal tubular acidosis (type I and II) or by renal tubular syndrome (Bartter's, Gitelman's and Liddle's syndrome). Bartter's syndrome, originally described by Batter and colleagues in 1962, is a set of closely related renal tubular disorders characterized by hypokalemia, hypochloremia, metabolic alkalosis and hyperreninemia with normal blood pressure. The underlying renal abnormality results in excessive urinary losses of sodium, chloride, potassium and calcium. Muscle weakness, polydipsia, polyuria and mental retardation can be also present. Affected children have poor growth rates and they appear malnourished. The article is focused on ethiopathogenesis, laboratory and clinical characteristics and on the treatment of Bartter's syndrome.
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PMID:[Bartter's syndrome--hypokalemic renal tubular syndrome]. 1462 62

A1A2 Na+/K+-ATPase mutations cause familial hemiplegic migraine type 2 (FHM2). The authors identified three putative A1A2 mutations (D718N, R763H, P979L) and three that await validation (P796R, E902K, X1021R). Ten to 20% of FHM cases may be FHM2. A1A2 mutations have a penetrance of about 87%. D718N causes frequent, long-lasting HM, and P979L may cause recurrent coma. D718N and P979L may predispose to seizures and mental retardation. A1A2 does not play a major role in sporadic HM; only one variant, R383H, occurred in 1 of 24 cases.
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PMID:Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase variants. 1515 95

Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inherited neurometabolic disorder clinically characterized by epilepsy and mental retardation and biochemically by accumulation of guanidinoacetate (GAA) and depletion of creatine. Although the neurological symptoms are predominant, the pathogenesis of the brain dysfunction in this disorder is not yet established. In the present study we investigated the in vitro effect of GAA on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic plasma membrane from hippocampus of young rats. Results showed that GAA significantly inhibited Na+, K+-ATPase activity without affecting Mg2+-ATPase activity. We also evaluated the effect of glutathione (GSH), trolox, Nomega-nitro-L-arginine methyl ester (L-NAME) and taurine (Tau) on the inhibition elicited by GAA on Na+, K+-ATPase activity. GSH, trolox, L-NAME and Tau per se did not alter Na+, K+-ATPase activity. However, L-NAME and taurine prevented the inhibitory effect of GAA on this enzyme activity. Our findings suggest that the inhibition of Na+, K+-ATPase activity caused by GAA is possibly mediated by nitric oxide (NO) formation and/or synaptic membrane alteration. The present data may contribute to the understanding of the neurological dysfunction characteristic of GAMT-deficient patients.
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PMID:Evaluation of the mechanism underlying the inhibitory effect of guanidinoacetate on brain Na+, K+-ATPase activity. 1524 54

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

'Severe myoclonic epilepsy in infancy' or Dravet syndrome is a clear example of the impact of severe epilepsy on the developing child. Presenting with febrile seizures in infancy, children later on develop a severe epileptic syndrome with mental retardation. Nearly all children have life-threatening status epilepticus during the first two years of life. The clinical diagnosis can now be confirmed by DNA-analysis in a majority of patients. Most patients have a de novo mutation in the alfa subunit of the neuronal sodium channel SCN1A. In the past few years' treatment of severe myoclonic epilepsy in infancy has changed. Prevention of seizures, avoiding anti-epileptic drugs which only block sodium channels, a simple combination of two major anti-epileptic drugs (sodium valproate and topiramate) and a strict acute seizure treatment significantly improve the quality of life for these patients. Long-term follow up is necessary to evaluate if we can also improve the development possibilities for these children.
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PMID:"Severe myoclonic epilepsy in infancy". Relevance for the clinician of severe epilepsy starting in infancy. 1550 61

Alternating hemiplegia of childhood (AHC) is a rare disorder mainly characterised by attacks of hemiplegia and mental retardation. AHC has often been associated with migraine. Previously, we have excluded the involvement of the familial hemiplegic migraine (FHM) CACNA1A gene in four patients with AHC. A second gene for FHM was discovered recently: the ATP1A2 gene on chromosome 1q23, coding for the alpha 2 subunit of Na+,K+-ATPase. We performed a mutation analysis of the ATP1A2 gene in six patients, using direct sequencing, but found no mutations in any of the 23 exons. Other cerebral ion channel genes remain candidate genes for AHC.
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PMID:Alternating hemiplegia of childhood: no mutations in the second familial hemiplegic migraine gene ATP1A2. 1553 63

Guanidinoacetate methyltransferase deficiency (GAMT deficiency) is an inherited neurometabolic disorder clinically characterized by epilepsy and mental retardation and biochemically by accumulation of guanidinoacetate (GAA) and depletion of creatine. Although this disease is predominantly characterized by severe neurological findings, the underlying mechanisms of brain injury are not yet established. In the present study, we investigated the effect of intrastriatal administration of GAA on Na+, K+-ATPase activity, total (tCK), cytosolic (Cy-CK), and mitochondrial (Mi-CK) creatine kinase (CK) activities in rat striatum. We verified that Na+, K+-ATPase, tCK, and Mi-CK activities were significantly inhibited by GAA, in contrast to Cy-CK which was not affected by this guanidino compound. Since these enzyme activities can be affected by reactive species, we also investigated the effect of intrastriatal administration of GAA on thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation in rats. We found that this metabolite significantly increased this oxidative stress parameter. Considering the importance of Na+, K+-ATPase and CK activities for brain metabolism homeostasis, our results suggest that the inhibition of these enzymes by increased intracerebral levels of GAA may contribute to the neuropathology observed in patients with GAMT-deficiency.
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PMID:Intrastriatal administration of guanidinoacetate inhibits Na+, K+-ATPase and creatine kinase activities in rat striatum. 1677 69

Eyelid myoclonia with absences (EMA) and juvenile myoclonic epilepsy (JME) are two separate epileptic syndromes included in the new classification of epilepsies and epileptic syndromes by ILAE in 2001. Both are idiopathic generalized epilepsies with their clinical onset in the first two decades. EMA is characterized by eyelid myoclonia associated with absences and photosensitivity. Self-induced seizures are frequently seen in EMA. It can be associated with mildly mental retardation and resistance to treatment. JME includes three types of generalized seizures: typical absences, myoclonic jerks and generalized tonic-clonic seizures. The myoclonic jerks occur almost exclusively on awakening, involve preferently the upper extremities, may rarely affect the lower extremities or the entire body. More severe attacks may be accompanied by a fall. The myoclonic jerks occur rarely in EMA. They are usually mild and are freqently restricted to the upper extremities. Generalized tonic-clonic seizures, photosensitivity and generalized polyspike-wave discharges provoked by eye closure are features of both epileptic syndromes. In this study, we describe four female patients with eyelid myoclonia associated with absences, myoclonic jerks causing falling down and rare generalized tonic-clonic seizures. All patients had good school performance and total seizure control under sodium valproate treatment. Their EEGs show generalized polyspike-wave discharges with a frequency of 3.5-6Hz always appearing a few seconds after eye closure and photoparoxysmal response. These patients show the characterictics of both epileptic syndromes. It is clinically important to make a syndromic diagnosis for an optimum advise on treatment, lifestyle restrictions and prognosis. In this study, we have gathered evidence that EMA and JME are dynamic syndromes that tend to evolve into one another.
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PMID:Overlap cases of eyelid myoclonia with absences and juvenile myoclonic epilepsy. 1750 53


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