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Research Notes: PWS Abstracts - 2004[ 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 2000 | 1999 | 1998 | 1997 | 1996 | 1995 | 1994 | 1993 | 1992 | 1991 | 1990 | 1980-1989 | 1979 and prior ] Eur J Anaesthesiol. 2004 Oct. No abstract available. Eur J Endocrinol. 2004 Oct. OBJECTIVE: Obesity and growth hormone (GH) deficiency are common in Prader-Willi syndrome (PWS) and these patients are at risk of metabolic diseases in adult life and of reduced life span. Low adiponectin values are associated with obesity and the metabolic syndrome. We therefore found it of interest to measure adiponectin levels in PWS. PATIENTS AND METHODS: 17 adults, nine men and eight women, 17 to 32 years of age, with a mean body mass index (BMI) of 35+/-3.2 kg/m2 participated. All had clinical PWS. They were randomized to treatment with placebo or GH (Genotropin) for six months, and subsequently all received GH for 12 months. At baseline, serum total adiponectin levels in the PWS patients were compared with 25 lean and 34 obese controls. Body composition and various metabolic parameters, including adiponectin, were studied every six months in the PWS group. RESULTS: Serum adiponectin levels in PWS subjects were significantly lower (P<0.001) compared with lean and significantly higher (P<0.001) compared with obese controls. In PWS patients, no correlation was found between adiponectin and anthropometrical parameters or measures of insulin sensitivity (e.g. fasting insulin and insulin sensitivity as estimated by the homeostasis model assessment), or between adiponectin and IGF binding protein-1 or IGF-I. Adiponectin did not change during GH intervention. CONCLUSION: In this study of adults with PWS serum total adiponectin levels were higher than in controls with simple obesity and were independent of anthropometrical parameters. In accordance with this the metabolic syndrome is not necessarily present in all PWS patients. Correction of GH deficiency had no effect on serum adiponectin levels. Arch Neurol. 2004 Oct. Background: Prader-Willi syndrome (PWS) is a genetic developmental disorder, mostly caused by a deletion on the paternal chromosome 15 or by a maternal uniparental disomy 15. Some PWS clinical and neurochemical features suggest an involvement of the corticospinal motor structures. Objective: To explore the corticospinal physiology of PWS by transcranial magnetic stimulation. Setting: A community-based hospital. Methods: We studied motor evoked potentials in the first dorsal interosseous muscle of 21 young-adult patients with PWS. Thirteen patients had a deletion at chromosome 15; 8 had a uniparental disomy. We measured the following variables: relaxed motor threshold, central motor conduction time, duration of the central silent period, and short-interval intracortical inhibition and facilitation. We also recorded F waves in the first dorsal interosseous muscle. We had 11 normal controls. Results: In the whole PWS group, motor threshold was higher as compared with controls (P<.05). The central motor conduction time, central silent period, and F waves were normal. Intracortical facilitation was reduced significantly (P<.001). Patients with PWS and a deletion had a weaker intracortical inhibition as compared with patients with PWS and a uniparental disomy (P<.05). Conclusions: Transcranial magnetic stimulation changes in patients with PWS suggested a hypo-excitability of the motor cortical areas. Defective neurogenesis of the cortical tissue and multiple transmitter alterations are the putative causes. Impaired intracortical inhibition might represent an electrical marker for a deletion defect. J Pediatr Endocrinol Metab. 2004 Sep. An insatiable appetite is a cardinal feature of Prader-Willi syndrome (PWS) with stomach rupturing as a reported consequence. Peptide YY, secreted by the intestine and released post-prandially, inhibits appetite, while ghrelin, secreted by the stomach during mealtime hunger, stimulates appetite. Both peptide YY and ghrelin act at the brain level, particularly the hypothalamus. Recently, plasma ghrelin levels were reported to be elevated in children and adults with PWS but peptide YY levels have not been studied in this syndrome or ghrelin in infants with PWS. To further address the abnormal eating behavior in PWS, we obtained fasting plasma peptide YY and ghrelin levels in 12 infants and children with PWS ranging in age from 2.5 months to 13.3 years and compared them with values from normal populations reported in the literature. Plasma ghrelin levels in our patients with PWS were similar to those of other children with PWS and were significantly higher than those reported in obese children without PWS. Our infants with PWS had similar plasma ghrelin levels compared with our children with PWS but peptide YY levels in our children and infants with PWS were lower than reported in similarly aged individuals without PWS. In addition, we performed preliminary gene expression analysis of ghrelin and peptide YY and their receptors in patients with PWS using established lymphoblastoid cell lines but gene expression did not correlate with plasma ghrelin or peptide YY levels. J Pediatr Endocrinol Metab. 2004 Sep. Prader-Willi syndrome (PWS) is characterized by hypothalamic dysfunction resulting in obesity, hypotonia, hypogonadism, and behavioral abnormalities. Clinical features of PWS resemble those of GH deficiency (decreased total lean body mass, IGF-I levels, and poor linear growth). Marked reductions in muscle mass are associated with diminished strength, physical function, and energy expenditure. Lifelong morbidities of PWS include osteoporosis, type 2 diabetes mellitus, respiratory disorders, and cardiorespiratory failure related to obesity and hypotonia. Recent studies show that GH therapy improves linear growth, final height, physical strength, and agility in patients with PWS. Some effects of GH therapy wane with time, however, and strategies for treating adults with PWS remain uncertain. In addition, deaths in markedly obese, GH-treated children with PWS have been reported, and a possible contribution of GH to these events has not yet been definitively excluded. Consequently, critical evaluation should continue of the long-term benefits, risks, and costs of GH therapy for patients with PWS. J Mol Med. 2004 Aug. More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B(1) deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals. Am J Med Genet A. 2004 Jun 15. The Prader-Willi syndrome (PWS) is a genetically determined developmental disorder caused by abnormalities of the proximal region of chromosome 15q11-13. In a previous study, we reported that psychotic episodes, occurring in 16% of persons with PWS, had an onset in adolescence, never occurred in persons with paternal deletion, and were exclusively associated with maternal uniparental disomy (UPD) or imprinting abnormalities (IM). In order to gain a better understanding of the psychopathology and to further refine the psychiatric diagnosis, we describe in more detail the psychopathological manifestations of six adults with a history of psychotic episodes. All these individuals had a detailed psychiatric examination, including the use of the operational criteria (OPCRIT) checklist. An identifiable subtype of psychotic disorder was associated with PWS. Characteristics include early age of onset, acute onset, polymorphous, and shifting symptomatology and a need for psychiatric hospitalization. The presence of precipitating stress factors and a prodromal phase with physiological symptoms was reported in all patients. Current diagnostic categories do not allow an unequivocal psychiatric diagnosis. Neuroimage. 2004 May. Prader-Willi syndrome (PWS) is a multi-system disorder characterized clinically by abnormal mental and physical development. PWS patients have a deletion in an imprinted region on paternal chromosome 15 (15q11-13), maternal disomy for this segment, or rarely, a chromosomal imprinting center deletion that gives rise to suppression of the equivalent paternal genes. Within the affected segment of chromosome 15 are genes encoding the alpha(5), beta(3) and gamma(3) subunits of the gamma-aminobutyric acid type-A (GABA(A)) receptor. Therefore, altered neurobehavioral function could arise in PWS due directly to altered GABA(A) receptor composition and expression, or alternatively, from brain developmental and maturational effects of these or other genes in the imprinted region. The aim of the present study was to assess cerebral GABA(A) receptors in PWS with the use of positron emission tomography of the benzodiazepine binding site employing [11C]flumazenil ([11C]FMZ). A reduction in [11C]FMZ binding was found predominantly in the cingulate, frontal and temporal neocortices and insula in six adult PWS patients compared to nine normal subjects. A possible role for the deleted beta(3) subunit gene in PWS is supported in part by the wide cortical distribution of its mRNA expression and the effects of experimental knockouts on benzodiazepine binding described in prior studies. Altered GABA(A) receptor composition or number in these cortical regions may account for neurobehavioral abnormalities in PWS including mild mental retardation, poor impulse control, and impaired responses to somatic pain. J Pediatr. 2004 May. OBJECTIVES: To study bone mineral status, body composition, and biochemical markers of bone turnover in Prader-Willi syndrome (PWS). STUDY DESIGN: Eight subjects with PWS (three males, five females; mean age, 24 years [range 16-41]) were included. Each subject was compared with an age-, sex- and body mass index-matched control randomly drawn from the background population. Bone mineral density (BMD), lean body mass, and fat mass were measured. Plasma PINP, PIIINP, osteocalcin, total alkaline phosphatase, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, and urine cross-linked N-terminal telopeptide of type I collagen were measured as biochemical markers of bone and collagen turnover. RESULTS: The PWS patients had significantly lower whole-body BMD (mean +/- SD, 1.020 +/- 0.041 vs 1.237 +/- 0.118 g/cm(2); 2p <.01) than controls due to lower bone mineral content (BMC: 2291 +/- 607 vs 2825 +/- 409 g; 2p=.02). Resorptive and formative bone markers were significantly elevated in patients compared with controls. Plasma testosterone was low in male patients (3.50 +/- 4.97 vs 19.2 +/- 8.78 nmol/L, 2p=.05), whereas no difference in plasma estradiol was present. CONCLUSIONS: The patients had a low BMD due to a high bone turnover. This high turnover was probably linked to sex steroid deficiency. Am J Ment Retard. 2004 May. Compulsive behavior in Prader-Willi syndrome is well-documented, though the neurochemical basis of these behaviors remains unknown. We studied a group of 16 people with Prader-Willi syndrome and a comparison group of 19 people with intellectual disability. Using eye-blink rate as an indirect measure of central nervous system dopamine, we found a higher eye-blink rate in the Prader-Willi syndrome group and a relationship between compulsive behavior and eye-blink rate across both groups. Our findings indicate a relationship between compulsions and an indirect measure of dopamine in people with intellectual disability. Our findings may provide evidence for a gene-brain-behavior link between dopamine levels and GABAergic mechanisms in individuals with Prader-Willi syndrome. Hum Mol Genet. 2004 Mar 15. Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG-binding protein 2 (MeCP2). Although MECP2 is ubiquitously transcribed, MeCP2 expression is developmentally regulated and heterogeneous in neuronal subpopulations, defined as MeCP2(lo) and MeCP2(hi). To test the hypothesis that pathways affecting MeCP2 expression changes may be defective in RTT, autism and other neurodevelopmental disorders without MECP2 mutations, a high-throughput quantitation of MeCP2 expression was performed on a tissue microarray containing frontal cortex samples from 28 different patients with neurodevelopmental disorders and age-matched controls. Combined quantitative analyses of MeCP2 protein and alternatively polyadenylated transcript levels were performed by laser scanning cytometry and tested for significant differences from age-matched controls. Normal cerebral samples showed an increase in total MeCP2 expression and the percentage of MeCP2(hi) cells with age that could be explained by increased MECP2 transcription within the MeCP2(hi) population. A significant decrease in the relative usage of the long transcript in the MeCP2(lo) population was observed in postnatal compared to fetal brain, but alternate polyadenylation did not correlate with MeCP2 expression changes at the single cell level. Brain samples from several related neurodevelopmental disorders, including autism, pervasive developmental disorder, Prader-Willi and Angelman syndromes showed significant differences in MeCP2 expression from age-matched controls by apparently different transcriptional and post-transcriptional mechanisms. These results suggest that multiple pathways regulate the complex developmental expression of MeCP2 and are defective in autism-spectrum disorders in addition to RTT. My abstract :-) Rett syndrome is a neurodevelopmental disorder that presents with cognitive impairment and autistic behavior and is caused by mutations in the MECP2 gene (on chromosome X) which carries the instructions for making methyl-CpG-binding protein 2 (MeCP2). The MeCP2 protein, which is found throughout both fetal and adult brains, has two different forms - a short form which contains a 1.9 kb transcript from the MECP2 grene and a long form which contains a 10 kb-long transcript that includes the 1.9 kb coding region of MECP2 as well as an exceptionally long untranslated region. Too make things more complicated, some brain neurons have relatively high levels of the MeCP2 protein and are called MeCP2(hi) neurons, while other neurons have relatively low levels of MeCP2 and are called MeCP2(lo) neurons. MeCP2 expression is developmentally regulated, that is, there are changes in the total amount of MeCP2 protein in the brain according to age, as well as changes in the amounts of short and long transcript forms of MeCP2 and changes in the number of MeCP2(lo) and MeCP2(hi) neurons. During normal brain development, the total amount of MeCP2 increases and there is a progressive increase in the number of MeCP2(hi) neurons from infancy to adulthood. At the same time, the amount of long-transcript MeCP2 falls relative to the amount of short-transcript MeCP2, even though juvenile and adult MeCP2(hi) neurons have more long-transcript MeCP2 than juvenile and adult MeCP2(lo) neurons. In PWS, there are significantly higher MeCP2 levels in the MeCP2(hi) neurons compared to control subjects, even though total MECP2 levels are significantly lower. In addition, there are higher levels of both short and long-transcript MECP2 proteins in PWS. In other words, PWS brains do not shift to more MeCP2(hi) neurons during growth, nor does the normal fall in the amount of long-transcript MeCP2 occur. That means that the loss of expression of the genetic information on the paternal chromosome 15 gene that occurs in PWS somehow affects the expression of the MECP2 gene on chromosome X. J Pediatr Endocrinol Metab. 2004 Mar. A 13 year-old boy with Prader-Willi syndrome and steatohepatitis presented with diabetic ketoacidosis 4 weeks after the initiation of growth hormone (GH) treatment. He did not have signs or symptoms of type 2 diabetes mellitus (DM2) before the initiation of GH treatment. Hyperglycemia resolved 2 months after discontinuation of GH. He redeveloped DM2 6 months later associated with excessive weight gain. Diabetic ketoacidosis as a rare complication of GH therapy emphasizes the importance of screening for carbohydrate intolerance before and during GH treatment in patients with Prader-Willi syndrome. Steatohepatitis may be the only manifestation of insulin resistance and warrants further evaluation. [Note: Steatohepatitis is characterized by inflammation of the liver together with the accumulation of fat in the liver. It is classically found in alcoholics, but is also frequently found in people with diabetes and obesity, in which case it is called "non-alcoholic steatohepatitis" (NASH). Both types can progress to cirrhosis.] Am J Ment Retard. 2004 Mar. Although maladaptive and compulsive behaviors are increasingly well-described in young persons with Prader-Willi syndrome, it is unclear how these problems manifest in older adults with this syndrome. In Part I, I compared maladaptive and compulsive behaviors in 45 older adults with Prader-Willi syndrome (ages 30 to 50 years) to 195 children, adolescents, and young adults. Young adults were at highest risk for problems. In contrast, maladaptive and compulsive symptoms diminished significantly in older adults with Prader-Willi syndrome. In Part II, I examined predictors of problems other than age: IQ, gender, BMI, and-for adults-living status. Gender and BMI were significant predictors of skin-picking and other symptoms. Possible reasons are discussed for sweeping declines in problems among older adults. Horm Metab Res. 2004 Mar. Ghrelin is a 28-amino acid peptide recently identified in the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Ghrelin is a potent stimulator of GH secretion. It was recently shown that circulating ghrelin levels in humans rise shortly before and fall shortly after every meal, and that ghrelin administration increases voluntary food intake. The hypothesis that ghrelin hypersecretion might contribute to genetic obesity has never been investigated. In this context, Prader-Willi syndrome is the most common form of human syndromic obesity. As ghrelin affects appetite as well as GH secretion and both are abnormal in PWS, it has been surmised that these alterations might be due to ghrelin dysregulation. The aim of the study was to investigate whether ghrelin is suppressed by the meals differently in PWS children than in PWS adults. Overnight circulating fasting ghrelin levels and ghrelin levels 120 min after breakfast were assayed in 7 PWS children (10.2 +/- 1.7 yr), 7 subjects with morbid obesity (10.3 +/- 1.3 yr), and 5 normal controls (8.4 +/- 1.4 yr). Because of the data spread, no statistical difference was observed in fasting ghrelin levels between PWS and control children (p = NS); anyway, fasting ghrelin levels were significantly lower in obese children than in the other groups (p < 0.05 vs. control and PWS children). Ghrelin levels were slightly suppressed by the meal in control subjects (mean fasting ghrelin: 160.2 +/- 82 pg/ml; after the meal, 141.2 +/- 57 pg/ml, p = NS); the meal failed to suppress ghrelin levels in obese children (mean fasting ghrelin: 126.4 +/- 8.5 pg/ml; after the meal, 119.1 +/- 8.3 pg/ml, p = NS). Interestingly, the meal markedly suppressed ghrelin levels in PWS children (mean fasting ghrelin: 229.5 +/- 70.4 pg/ml; after the meal, 155.8 +/- 34.2 pg/ml, p < 0.01). In conclusion, since a lack of decrease in circulating ghrelin induced by the meal was previously reported in PWS adults, the finding of a meal-induced decrease in ghrelin levels in our population of young PWS would imply that the regulation of the ghrelin system involved in the orexigenic effects of the peptide is operative during childhood, although it progressively deteriorates and is absent in adulthood when hyperphagia and obesity progressively worsen. J Intellect Disabil Res. 2004 Feb. BACKGROUND: Prader-Willi syndrome (PWS) is characterized by extreme floppiness at birth, impaired sexual development, short stature, severe over-eating, characteristic physical features and learning disabilities (LD). Impaired social cognition, literal mindedness and cognitive inflexibility are also present. The syndrome has two main genetic subtypes that both result in the failure of expression of maternally imprinted genes on chromosome 15 at the locus q11-13. METHODS: Through multiple sources, we attempted to identify all people with PWS living in one health region in the UK. Additional people with PWS identified in other regions were also recruited to augment the study sample. A comparison group of people with LD as a result of aetiologies other than PWS was also identified. All people from these three groups, over age three, who gave their consent, were assessed using tests of ability and attainment. In addition, their main carers were interviewed using a semistructured interview. Blood samples for genetic diagnosis were obtained from all consenting participants. FINDINGS: The IQ distribution of the population sample was approximately normal with a mean IQ 40 points below that of the general population. There were systematic differences between the two main genetic subtypes. Those with disomies differed in cognitive profiles from both those with deletions and the comparison LD group (the latter two groups were very similar) in terms of better verbal abilities and impaired coding ability. Some people with PWS deletions had strong visuospatial skills. INTERPRETATION: We propose that the normal distribution of IQ, shifted downwards relative to that of the general population, is the result of a global effect on IQ of the PWS gene(s), and that the different cognitive profile seen in those with chromosome 15 maternal disomies is a specific effect of a gene, or genes, on chromosome 15 which is differentially either expressed or not expressed in those with disomies relative to those with deletions. One hypothesis is that these subtle cognitive differences are a manifestation of the genetic influences of gender-specific imprinted genes on cerebral lateralization. This requires further investigation. Eur Child Adolesc Psychiatry. 2004 Feb. Prader Willi Syndrome (PWS) is a neuro-genetic disorder. It has been reported that cases due to paternal deletion 15q11-13 (Del) behave differently to cases due to uniparental disomy (UPD). Comparison of the two forms of PWS has, to date, not included the frequency of autistic behaviours, even though there are reports of an association between maternal duplications of 15q11-13 and autism spectrum disorders (ASD). It was predicted that maternal UPD PWS cases would be more prone to ASD than Del PWS cases due to their duplicated maternally expressed genes. A preliminary test of the hypothesis was conducted using postal and telephone surveys of matched, genetically verified, UPD and Del cases using the Autism Screening Questionnaire (ASQ) and the Vineland Adaptive Behaviour Scales (VABS). As predicted, UPD cases were reported as exhibiting significantly more autistic symptomatology. They also were born to older mothers and were reported on the VABS to have more deficits in motor control problems and fewer adaptive skills in the Daily Living Skills domain. Del cases were reportedly more skilled at jigsaw puzzles. The results lend further support to the notion that abnormality in the expression of maternal imprinted 15q11-13 genes may confer a susceptibility to ASD. They also suggest that there may be cognitive differences between the groups in processing visuo-spatial information. J Intellect Disabil Res. 2004 Feb. BACKGROUND: Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder that is associated with the under-expression of maternally imprinted genes at the 15q11-q13 chromosomal locus. In addition to a characteristic physical and behavioural phenotype, those with the syndrome have impaired social cognition, literal mindedness and inflexibility. The present authors investigated the relationship between the PWS cognitive and behavioural phenotype, educational experience, and levels of attainment in reading, writing and arithmetic. METHODS: All subjects from a population-based sample of people with PWS, augmented by those with PWS living in other regions together with a contrast group of people with learning disability (LD) of other aetiologies, are included in the present study. Those children over 3 years of age whose families consented or adults who themselves consented were assessed for ability and attainment (over 7 years of age), and information on functional ability was also obtained from an informant. Underachievement was defined as the difference between the score predicted from full-scale IQ and the actual achievement score. RESULTS: Commonly, levels of achievement were lower than would have been predicted on the basis of IQ among those in the groups with PWS and LD. In the group with PWS, underachievement across academic domains was positively correlated with the percentage of time in education in a special school and negatively correlated with Vineland Socialization domain standard score. There were no across-domain significant correlations in the group with LD. When using multiple regression analysis, the percentage of time in special school was the only predictor of underachievement and only in the group with PWS. However, some children with PWS in special schools did achieve as expected in at least one academic domain. CONCLUSIONS: Children with PWS may be placed in special schools largely because of their behavioural problems or physical disabilities, or expectations based on their PWS status. Their intellectual abilities may well be masked by their immature social behaviour. The present authors propose that a failure to recognize and address the specific educational needs which follow from this combination of poor socialization skills and complex maladaptive behaviours, in the context of relatively mild LD, may explain their findings. Growth Horm IGF Res. 2004 Feb. Prader-Willi syndrome (PWS) is a genetic disorder characterized by mild mental retardation, short stature, abnormal body composition, muscular hypotonia and distinctive behavioural features. Excessive eating causes progressive obesity with increased cardiovascular morbidity and mortality. In the PWS genotype loss of one or more normally active paternal genes in region q11-13 on chromosome 15 is seen. It is supposed that the genetic alteration leads to dysfunction of several hypothalamic centres and growth hormone (GH) deficiency (GHD) is common. PWS is well described in children, in whom GH treatment improves body composition, linear growth, physical strength and agility. Few studies have focused on adults. We examined a cohort of 19 young adults with clinical PWS (13 with positive genotype) and mean BMI of 35 kg/m2. At baseline the activity of the GH-insulin-like growth factor-I (IGF-I) system was impaired with low GH values, low total IGF-I and in relation to the obesity low levels of free IGF-I and non-suppressed IGF-binding-protein-1 (IGFBP-1). 2/3 were hypogonadal. Bone mineral density (BMD) was low. Four patients had impaired glucose tolerance and nine patients high homeostasis model assessment (HOMA) index, indicating insulin resistance. Seven patients had a moderate dyslipidemia. The 13 patients with the PWS genotype were shorter and had significantly lower IGF-I. Seventeen (9 men and 8 women), subsequently completed a 12 months GH treatment trial, and GH had beneficial effects on body composition without significant adverse effects. The effects were more pronounced in the patients with the PWS genotype. Analysis of peptides involved in appetite regulation showed that leptin levels were high reflecting obesity and as a consequence NPY levels were low. In relation to the patients obesity circulating oxytocin levels were abnormally low and ghrelin levels abnormally high. Thus, oxytocin and ghrelin might be involved in the hyperphagia. NPY, leptin and ghrelin did not change during GH treatment. In conclusion this pilot study showed that adults with PWS have a partial GH deficiency, and GH treatment has beneficial effects on body composition in adult PWS without significant side-effects. Larger and longer term studies on the effect of GH replacement in adult PWS are encouraged. Trends Endocrinol Metab. 2004 Jan-Feb. Prader-Willi syndrome (PWS) is a complex human genetic disease that arises from lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. Identification of the imprinting control centre, novel imprinted genes and distinct phenotypes in PWS patients and mouse models has increased interest in this human obesity syndrome. In this review I focus on: (i) the chromosomal region and candidate genes associated with PWS, and the possible links with individual PWS phenotypes identified using mouse models; (ii) the metabolic and hormonal phenotypes in PWS; (iii) postmortem studies of human PWS hypothalami; and (iv) current and potential advances in the management of PWS and its complications. This could have benefits for a wide spectrum of endocrine, paediatric and neuropsychiatric diseases. Am J Med Genet A. 2004 Jan 15. Individuals with Prader-Willi syndrome (PWS) generally survive into adulthood. Common causes of death are obesity related cor pulmonale and respiratory failure. We report on a case series of eight children and two adults with unexpected death or critical illness. Our data show age-specific characteristics of PWS patients with fatal or life-threatening illnesses. Under the age of 2 years, childhood illnesses in general were associated with high fever and rapid demise or near-demise. Hypothalamic dysfunction likely plays a role in exaggerated fever response, but also perhaps in central regulation of adrenal function. Below average sized adrenal glands were found in three children, which raises the possibility of unrecognized adrenal insufficiency in a subset of individuals with PWS and emphasizes the vital role of autopsy. The tub drowning death of an adult patient could be related to central hypersomnia [or cataplexy?], which has been reported in PWS. We suggest that increased risk for critical illness be considered in the discussion of anticipatory guidance for the care of infants with PWS. Since a number of children died while hospitalized, particularly close observation of PWS children who are ill enough to warrant hospital admission is recommended. J Pediatr. 2004 Jan. A 4-year-old boy with Prader-Willi syndrome died suddenly while asleep on day 67 of growth hormone treatment. During treatment, snoring had worsened. Autopsy showed multifocal bronchopneumonia. This case and two others recently published suggest that growth hormone may be associated with obstructive apnea, respiratory infection, and sudden death in this condition. Horm Res. 2004. Background: Elevated plasma ghrelin levels have recently been reported in adults and children with Prader-Willi syndrome (PWS). The aim of the study is to investigate the relationship between obesity, growth hormone (GH) deficiency (GHD) and ghrelinemia in PWS and to examine whether hyperghrelinemia is specific to PWS. Methods: We measured fasting ghrelinemia in children with PWS, idiopathic GHD (iGHD), obese children, controls and in 6 children presenting another congenital syndrome associated with GHD: pituitary stalk interruption (PSI). Results: Children with PWS exhibited significantly higher ghrelin levels (995 pg/ml (801/1,099, median 1st/3rd quartile)) than iGHD (517 pg/ml (392/775)), obese (396 pg/ml (145/610)) and control (605 ng/ml (413/753)) children. Similar to PWS hyperghrelinemia was found in PSI children (1,029 pg/ml (705/1,151)), and was not modified by GH treatment. Conclusion: We conclude that hyperghrelinemia in PWS and PSI is not related to GH secretion. We hypothesize that a major site of ghrelin action is at the hypothalamic level and that a 'ghrelin resistance' syndrome may be present in these patients, primarily due to a hypothalamic defect. Combined alterations such as impaired serotonin receptor regulation associated with abnormal ghrelin responsiveness are probably responsible for obesity in PWS. Treat Endocrinol. 2004. Prader-Willi syndrome is a complex genetic disorder with a characteristic cognitive, behavioral, and endocrinologic phenotype. Obesity, partial growth hormone (GH) secretion, and hypogonadism are common. Results of several somatropin (GH therapy) studies in children with Prader-Willi syndrome have shown improvement in growth, body composition, physical strength, and agility. GH deficiency in adults without Prader-Willi syndrome is associated with abdominal obesity, insulin resistance, and an unfavorable lipid profile, and the partial state of GH deficiency seen in Prader-Willi syndrome thus renders these patients exposed to a lifelong risk of metabolic diseases. The nongrowth effects of somatropin in children with Prader-Willi syndrome have directed interest towards adults in preventing long-term consequences of GH deficiency, but the potential impact of somatropin therapy in adults with Prader-Willi syndrome is not known in detail. To date, only one study has been published. In this study, 17 patients (9 men and 8 women) with a mean age of 25 years and a mean body mass index of 35 +/- 3.2 kg/m2 were examined. Eleven had the Prader-Willi syndrome genotype. They were treated with somatropin (Genotropin) for 12 months after an initial placebo-controlled period of 6 months. Compared with placebo, somatropin increased insulin-like growth factor-1 levels (p < 0.01) and decreased body fat (p = 0.04). During the 12-month period with somatropin therapy, the mean reduction in body fat was 2.5% (p < 0.01), concomitant with a mean increase in lean body mass of 2.2kg (p < 0.05). Lipid profiles were normal in most patients before treatment and did not change. The oral glucose tolerance test was impaired in one patient at study start and in five patients at 12 months. No patients developed diabetes mellitus. Furthermore, insulin levels remained unchanged, and estimation of insulin resistance by homeostasis model assessment did not disclose any change. Transient adverse effects attributed to water retention occurred in three patients. In conclusion, the one published study of somatropin therapy in adults with Prader-Willi syndrome showed beneficial effects on body composition without pronounced adverse effects. However, further studies are required to establish the definite role and optimal dosage of somatropin, as well as long-term effects, in adults with Prader-Willi syndrome. [ 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 2000 | 1999 | 1998 | 1997 | 1996 | 1995 | 1994 | 1993 | 1992 | 1991 | 1990 | 1980-1989 | 1979 and prior ] |