Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ornithine transcarbamylase deficiency is an X linked disorder and the most common inherited cause of hyperammonaemia. Fluctuating concentrations of ammonia, glutamine, and other excitotoxic amino acids result in a chronic or episodically recurring encephalopathy. A heterozygous female patient first presented with protein intolerance, attacks of vomiting, and signs of mental retardation in early childhood. At the age of 16 complex partial seizures occurred which were treated with sodium valproate. Seven days after initiation of valproate therapy, she developed severe hyperammonaemic encephalopathy with deep somnolence. The maximum concentration of ammonia was 480 micromol/l. After withdrawal of valproate, three cycles of plasma dialysis, and initiation of a specific therapy for the inborn metabolic disease, ammonia concentrations fell to normal values. The patient remitted, returning to her premorbid state. Valproate can cause high concentrations of ammonia in serum in patients with normal urea cycle enzymes and may worsen a pre-existing hyperammonaemia caused by an enzymatic defect of the urea cycle. Sufficient diagnostic tests for the detection of metabolic disorders must be performed before prescribing valproate for patients with a history of encephalopathy.
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PMID:Hyperammonaemic encephalopathy after initiation of valproate therapy in unrecognised ornithine transcarbamylase deficiency. 959 92

Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly and mental retardation syndrome caused by an interstitial deletion of chromosome 17 p11.2. Although the physical and molecular genetic features of SMS are increasingly well understood, work is more limited on SMS's behavioral phenotype, which includes self-injury, tantrums, and sleep disturbance. This study examines the sleep behaviors of 39 individuals with SMS, ranging in age from 1.6 to 32 years (mean = 10.5). Prominent sleep problems, seen in 65 to 100% of the sample, included difficulties falling asleep, shortened sleep cycles, frequent and prolonged nocturnal awakenings, excessive daytime sleepiness, daytime napping, snoring, and bed-wetting. Medication to facilitate sleep was used by 59% of SMS subjects. Possible etiologic mechanisms of sleep disturbance in SMS are discussed, as are recommended interventions.
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PMID:Sleep disturbance in Smith-Magenis syndrome (del 17 p11.2). 961 60

Shaken baby syndrome is a serious form of physical child abuse, which is frequently overlooked. It should be suspected in all children younger than one year of age, who present with drowsiness, coma, seizures or apnoea. A combination of subdural haematomas and retinal haemorrhages with minimal or no trauma and no coagulopathy is almost pathognomonic of the syndrome. The findings are caused by shaking with or without impact. Physical signs of violence are often absent and the syndrome may easily be mistaken for serious infection or seizure disorder. Many cases are fatal or lead to severe disability including blindness, cerebral palsy, mental retardation or epilepsy in about 60% of the children. There are many unresolved problems regarding diagnosis, pathophysiology, treatment, prognosis, prophylaxis and legal actions. We discuss these problems and in addition present eleven children with shaken baby syndrome.
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PMID:[Shaken baby syndrome]. 982 79

BACKGROUND: Prader-Willi Syndrome (PRWS) is an uncommon neuroendocrine disorder of genetic origin, described in 1956 by Prader, Labhart and Willi. The main clinical manifestations in the adult are mental retardation, hyperphagia with gross obesity, hypogonadismcriptorhismus and short stature. The life expectancy of the affected individual ranges between 20 and 30 years rarely beyond - due to complications related to excessive obesity. Sustained dieting combined with behavior modification programs, as well as gastric restrictive surgery for obesity, proved to have a high failure rate in PRWS, due to the patients' inability to cooperate in changing their eating habits. METHODS: Biliopancreatic Diversion (BPD), which does not require the patient's cooperation in changing eating habits after surgery, was performed in two PRWS patients (13- and 22-years-old), both with excessive obesity, severe respiratory distress, day sleepiness and limited mobility. RESULTS: Two years after surgery, the 13-year-old had lost 80% of her overweight, while the 22-year-old, after 1 year, had lost 34%. Recent laboratory tests showed normal data in both patients. Their respiratory distress had subsided completely, their mobility improved dramatically, and their self-image and alertness enhanced. CONCLUSION: BPD resulted in an improved quality of life in these patients.
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PMID:Biliopancreatic Diversion in Prader-Willi Syndrome Associated with Obesity. 1073 Dec 52

A 12-week, double-blind, randomized, placebo-controlled trial of oral clonidine in three fixed doses (4, 6, and 8 mcg/kg/day) using a crossover design was conducted with 10 children who had hyperkinetic disorder (mean age 7.6 years +/-.54). All had comorbid mental retardation. Both parents' ratings on the Parent Symptom Questionnaire and clinicians' ratings on the Hillside Behaviour Rating Scale showed a marked dose-related response to clonidine in hyperactivity, impulsivity, and inattention. Drowsiness was a common side effect of clonidine. It wore off by the 2nd to 4th week in most cases. Thus, clonidine is a safe and effective medication in young hyperkinetic children with comorbid mental retardation.
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PMID:Double-blind, placebo-controlled trial of clonidine in hyperactive children with mental retardation. 1144 49

(1) Severe myoclonic epilepsy of infancy (Dravet's syndrome) is associated with multiple seizures and progressive onset of mental retardation. Available antiepileptics (valproic acid and clonazepam/clobazam) are only partially effective, even when used in combination. (2) Stiripentol is intended to be added to the valproate + clobazam combination when the latter is ineffective. (3) In a two-month double-blind trial, 9 of 21 infants remained seizure-free when stiripentol was added to the valproate-clobazam combination, whereas all 20 infants receiving a placebo instead of stiripentol continued to have seizures. (4) Two follow-up studies lasting two and three years and involving 37 and 46 children showed that about 20% of patients had a major benefit (fewer seizures) when stiripentol was added to inadequately effective valproate-clobazam combination therapy. The possible impact of stiripentol on psychomotor development is unknown. Stiripentol was only moderately effective in adolescents. (5) Stiripentol has common and sometimes serious adverse effects such as loss of appetite (with ensuing weight loss), drowsiness and insomnia. Stiripentol inhibits several cytochrome P450 isoenzymes, including CYP 3A4, creating a high risk of interactions, especially with co-administered antiepileptics. (6) The stiripentol dose strengths currently available in France are unsuitable for infants weighing less than 10 kg. (7) In practice, given the severity of this type of myoclonic epilepsy of infancy, the addition of stiripentol to ongoing but ineffective valproate-clobazam combination therapy is justified, even though the treatment is somewhat difficult to manage and has not yet been fully evaluated.
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PMID:Stiripentol: new preparation. Severe myoclonic epilepsy of infancy: promising. 1587 42

6-Pyruvoyltetrahydropterin Synthase (PTPS) deficiency is the most common cause of hyperphenylalaninemia due to tetrahydrobiopterin deficiency. The presenting symptoms of PTPS deficiency are mental retardation, convulsions, disturbance of tone and posture, drowsiness, irritability, abnormal movements, hypersalivation, and swallowing difficulties(1-3). The authors reported the first two cases of PTPS deficiency in Thailand. Both cases were male infants who showed phenylalanine levels of 25.23 mg/dl and 23.4 mg/dl respectively. The urinary pterins analysis showed low biopterin and high neopterin. The percentage of urinary biopterin was also found to be very low. The mutation analysis of the first case revealed a point mutation of exon 4, a homozygous C to T transition at nucleotide 200 in codon 67 (T67M), and the second case showed a compound heterozygous of exon 4, C to A transition at nucleotide 200, and exon 5, C to T transition at nucleotide 259 of the PTS gene confirming that they had PTPS deficiency. Treatment was started with neurotransmitters and a low phenylalanine diet. Family carriers were detected by means of urinary pterins determination and mutation analysis.
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PMID:6-pyruvoyltetrahydropterin synthase deficiency two-case report. 1685 Jun 90

Nocturnal frontal lobe epilepsy (NFLE) is a condition primarily characterized by seizures occurring exclusively or predominantly during sleep, the semiology of which suggest a frontal lobe origin and, more specifically, the involvement of the orbitofrontal or mesial frontal regions. It is usually considered as a relatively benign and homogeneous epileptic syndrome, the neuropsychological impact of which should be minimal. However, several issues complicate this view. 1. NFLE is rather a heterogeneous disorder which includes both sporadic and familial forms, various seizure types, and drug resistance in about 30% of patients. 2. The frontal origin of seizures has rarely been demonstrated, and mainly relies on the presence of ictal signs suggestive of frontal lobe epilepsy, but which might only reflect the propagation of ictal discharges of extrafrontal origin. 3. NFLE-like seizures were recently found to be associated with temporobasal cortical dysplasia, or an insular epileptogenic zone, including one patient with autosomal dominant frontal lobe epilepsy (ADNFLE). 4. No study has yet specifically evaluated the neuropsychological profile of patients with NFLE. Available data suggest that behavioral problems and mental retardation might be associated with ADNFLE, especially when it is related to a mutation of the nicotinic receptor subunits. Conversely, the majority of NFLE patients does not seem to present with gross cognitive disturbance, even though many of these patients complain of chronically disrupted sleep and daytime sleepiness. Further research is warranted in this field, keeping in mind that the neural networks underlying NFLE remain poorly known and might primarily involve extrafrontal brain regions in some patients.
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PMID:Nocturnal frontal lobe epilepsy. 1710 70

Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPD). Few cases have been described with mental retardation or neurological symptoms. Recently it has been demonstrated that 4-HPD participates to nitric oxide (NO) intracellular sequestration in Pseudomonas aeruginosa. 4-HPD is an ubiquitous enzyme with a prominent expression in neutrophils and neurons. In the nervous system NO has been perceived to be a potential neuromodulator although prolonged excessive generation is detrimental. We analyzed NO release by neutrophils of a patient with tyrosinemia type III in order to evaluate a possible influence of 4-HPD deficiency on this process. Our patient, previously described, is a 30-year-old women with persistent tyrosinemia (450-680 micromol/l) and deficient activity of 4-HPD. At 17 months of age she experienced an acute ataxia and drowsiness lasting for 10 days, but further clinical course showed persistent tyrosinemia with normal growth and psychomotor development. Neutrophils isolated from our patient exhibited a NO release greatly higher in respect to the controls (mean+/-SEM 23.2+/-1.8 micromol/10(6) cells vs 3.5+/-0.5 micromol/10(6) cells). Clinical findings of tyrosinemia type III include neurological symptoms and mental retardation but no consistent phenotype has emerged. Therefore the pathogenesis of neurological involvement is yet not well understood. Our results suggest that an excessive neutrophils of NO release could reflect the lack of scavenging action of 4-HPD. Considering the prominent expression of this enzyme in neurons, we hypothesize that excessive NO release could participate in neuronal damage explaining the neurological involvement described in patients with tyrosinemia type III.
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PMID:Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III. 1865 47

The ketogenic diet for the treatment of refractory epileptic encephalopathies has been suggested as an early treatment option in very young children. The aim of the present study was to assess the efficacy and tolerability of the ketogenic diet in children younger than 5 years, all affected by different types of catastrophic childhood encephalopathies. The study group is composed of 38 children (22 males and 16 females), aged between 3 months and 5 years, affected by symptomatic partial epilepsy (6) and cryptogenic-symptomatic epileptic encephalopathies (32). Psychomotor delay-mental retardation was present in all of the patients: mild to moderate (9), severe (7), and profound (22). Cerebral palsy was present in 74% of the cases. Children were started on a 4:1 ketogenic diet as ketocal formula alone or supporting about the 80% of the daily caloric amount. Children poorly complying with ketocal milk were shifted to a classic 4:1 ketogenic diet. The average time (months +/- S.D.) on the diet was 10.3 +/- 7.4. All the children initiating the diet remained on it at 1 month and 35 of them (92%) at 3 months, 28 (73.7%) remained on it at 6 months, and 20 (52.7%) at 1 year. At 12-month follow-up, 11 children (28.9%) had a greater than 50% reduction of seizures and the other 9 (23.7%) were seizure-free. Adverse side effects were recorded in 25 of 38 patients (65.8%), including drowsiness, constipation, weight loss, vomiting, gastroesophageal reflux, fever, and hyperlipidemia. This report confirms that severe epileptic encephalopathies are much suitable for the ketogenic diet.
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PMID:Ketogenic diet for the treatment of catastrophic epileptic encephalopathies in childhood. 1963 70


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