ABSTRACT
UNLABELLED: BACKGROUND, RATIONALE, AND METHODS: Lesch-Nyhan disease is a rare, X-linked disorder due to hypoxanthine phosphoribosyltransferase deficiency. To evaluate reported benefit on mood and behavior obtained by the administration of S-adenosyl-L-methionine in this condition, we developed 2 quantitative evaluation tools, and used them to assess the effects of the drug in our population: the weekly questionnaire and the resistance to self-injurious behavior test. We performed an open-label, dose-escalation trial of the drug on 14 patients. RESULTS: Four patients tolerated the drug and reported beneficial effects. The majority experienced worsened behavior. The 2 assessment tools demonstrated effectiveness in quantitatively evaluating the self-injurious behavior.
Subject(s)
Affect/drug effects , Behavior/drug effects , Hypoxanthine Phosphoribosyltransferase/metabolism , Lesch-Nyhan Syndrome/drug therapy , S-Adenosylmethionine/pharmacology , S-Adenosylmethionine/therapeutic use , Surveys and Questionnaires , Adolescent , Adult , Child , Dose-Response Relationship, Drug , Humans , Hypoxanthine Phosphoribosyltransferase/deficiency , Hypoxanthine Phosphoribosyltransferase/genetics , Lesch-Nyhan Syndrome/genetics , Middle Aged , Psychotropic Drugs/pharmacology , Psychotropic Drugs/therapeutic use , Treatment OutcomeABSTRACT
PURPOSE: To evaluate retrospectively the efficiency of our rehabilitation programme for patients with Prader-Willi Syndrome. In total, 49 patients were examined, 21 female and 28 male, the youngest in their late teens. Prader-Willi syndrome is generally characterised by cognitive impairment, behavioural abnormalities, and hyperphagia. Patients are usually considerably adverse to any form of physical exercise, and despite hormonal therapy, weight control in adult patients can be difficult. METHODS: Four times a year, disease-specific residential programmes were organised, each lasting 4 weeks. The patients were restricted to a 1500 Kcal diet. In addition, they were required to do 6.5 h of physical exercise daily, stamina being built up by using music therapy, psychomotor therapy, education and entertainment activities. RESULTS: BMI decreased by 2.1 average points in every residential session. For three patients who attended our treatments regularly, a reduction of 8.9 points over 6 years was recorded. An attendance of at least three sessions per year seemed to be necessary to substantially reduce weight. CONCLUSIONS: A multidisciplinary approach and a daily calorie-counted diet can lead to significant weight loss in teenage and adult PWS patients. This approach would also be suitable in treating patients with other obesity syndromes with mental retardation.
Subject(s)
Diet Therapy , Exercise Therapy , Music Therapy , Obesity/prevention & control , Prader-Willi Syndrome/rehabilitation , Absorptiometry, Photon , Adolescent , Adult , Body Mass Index , Diet, Mediterranean , Energy Intake , Female , Humans , Hyperphagia/etiology , Male , Obesity/complications , Prader-Willi Syndrome/complications , Prader-Willi Syndrome/therapy , Retrospective Studies , Weight Loss , Young AdultABSTRACT
BACKGROUND: Lesch-Nyhan (LND) disease is an inborn error of purine metabolism which results from deficiency of the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT). In the classical form of the disease the activity of the enzyme is completely deficient and the patient has cognitive impairment, spasticity, dystonia and self-injurious behaviour, as well as elevated concentrations of uric acid in blood and urine that leads to consequences such as nephropathy, urinary tract calculi and tophaceous gout. There are disease variants without self-injurious behaviour. In these cases neurological manifestations may vary widely. The HPRT1 gene is located on the X chromosome in position Xq26-27.2, and mutations have been found in quite a large number of patients. OBJECTIVE: Documenting our experience with the diagnosis of LND in 45 Italian patients from 35 nonrelated families and 77 females at risk of being carriers of the condition. DESIGN: Internal review. SETTING: An institute devoted to the investigation and care of patients with rare diseases. RESULTS: In 94% of the LND families gDNA sequencing of the patients was informative while in 6% a cDNA study was required. For the carrier females gDNA sequencing was informative in 71% of the families, 23% required qPCR studies and 6% required segregation studies combined with enzymatic activity testing. Classical cDNA studies proved to be unreliable in carrier females as there is a significant risk of failure to detect the mutated allele. Four novel HPRT1 mutations were found: c.145C>T (p.Leu49Phe), c.112C>T (p.Pro38Ser), c.89_96dup8 (p.Glu33Argfs) and c.506dupC (p.Arg170Thrfs). CONCLUSION: In the diagnosis of LND it is very important to consider all the possible alterations of the HPRT1 gene when searching for mutations especially if no affected male is available. Biochemical assessment of the enzymatic activity of HPRT in an affected male is the ideal starting point for molecular analysis of the gene.
