Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0020505 (hyperphagia)
6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OBJECTIVE: To describe 6 patients with less than 3 years of age that were diagnosed with Prader-Willi syndrome (PWS) due to hypotonia, poor sucking, slight facial anomalies and minor abnormalities of hands and feet. PWS is a neurobehavioural disorder characterized by two distinct phases; in the first, the neonate presents variable degree of hypotonia, feeding problems with none or poor sucking; hypogonadism, characteristic facial features with almond shaped eyes, narrow bifrontal diameter and down-turned corners of the mouth. Neuropsichymotor development is delayed. Hypotonia is non progressive and tends to improve between 8 and 11 months of age. The second phase then starts and is characterized by increasing hyperphagia and obesity, among other features. Unfortunately, most PWS patients are diagnosed only after obesity is installed. METHODS: Methylation, microsatellites analysis and karyotypic studies by traditional and in situ hybridization techniques were done. RESULTS: A deletion of chromosome segment 15q11q13 was disclosed in 4 and maternal disomy in two patients. CONCLUSION: The diagnosis of PWS is generally established after the onset of obesity. So, we suggest that the genetic analysis must be carried out in children with severe hypotonia of unknown cause, poor sucking and some facial features of PWS (small hands and feet, hypogonadism, hypopigmentation, almond eyes and narrow bifrontal diameter). This can allow the early diagnosis and avoid invasive exams necessary for neuromuscular disorder diagnosis like muscle biopsy and electroneuromiography, wich frequently are associated with inconclusives results.
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PMID:[Hypotonic infants and the Prader-Willi Syndrome] 1464 78

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.
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PMID:Endocrine and metabolic aspects of adult Prader-Willi syndrome with special emphasis on the effect of growth hormone treatment. 1470 May 52

Prader-Willi syndrome (PWS) is a complex genetic disorder. It is characterized by hypotonia, short stature, hypogonadism, mental retardation, behavioral problems, and hyperphagia, which result in excessive obesity (Lindgren et al., 2000). The abnormal body composition resembles children seen with growth hormone deficiency (Carrel & Allen, 2001) . The dysmorphic features characteristic of PWS include a narrow forehead, a broad nasal bridge, slightly up slanting almond-shaped palpebral fissures, a down turned mouth with a thin upper lip, and narrow hands and feet (Martin et al., 1998). Management of children with PWS requires an ongoing multidisciplinary approach. The delivery of care includes assistance from geneticists, nutritionists, internists, endocrinologists, physical therapists, and psychologists to meet the medical, developmental, behavioral, and social needs. The focus of the nurse practitioner should include assisting the family in the management of these complex patients throughout their childhood.
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PMID:Anticipatory guidance for parents of Prader-Willi children. 1474 37

Ghrelin and peptide YY (PYY) are peptides generally produced by the gastrointestinal organs which are involved in appetite regulation via highly specialized centers in the brain. Abnormal plasma ghrelin and PYY levels compared with controls have been reported for subjects with Prader-Willi syndrome (PWS) which is characterized by infantile hypotonia, poor suck reflex and failure to thrive followed by hyperphagia and marked obesity in early childhood. We studied gene expression of ghrelin, peptide YY, and their receptors (i.e., GHS-R1a, GHS-R1b, and NPY2R) in six different brain regions (frontal cortex, temporal cortex, visual cortex, pons, medulla, and hypothalamus) obtained from three subjects with PWS, two individuals with Angelman syndrome, and six controls to determine if expression of these genes is detectable in different regions of the brain in subjects with and without PWS. In general, expression of these genes using RT-PCR was detected in all subjects and no obvious differences were seen in their pattern of expression between subjects with or without PWS. Additional studies including quantitative gene expression measurements will be required to further evaluate the role of these genes in the eating disorder seen in PWS.
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PMID:Ghrelin, peptide YY and their receptors: gene expression in brain from subjects with and without Prader-Willi syndrome. 1575 36

Prader-Willi Syndrome (PWS) is a genetic disorder characterized by hypotonia, mental retardation or learning disability, hyperphagia and compulsive eating due to hypothalamic dysfunction. Obesity is a major cause of increased morbidity and mortality among patients with PWS. Gastric restrictive surgery has been associated with partial breakdown of the staple-line in PWS. We report two patients with PWS associated with morbid obesity and obstructive sleep apnea who underwent biliopancreatic diversion (BPD). A 27-year-old male with BMI 52 kg/m(2) and a 20 year-old female with BMI 64 kg/m(2) underwent BPD. No perioperative complications were observed. After BPD, the male's BMI was 36.7 kg/m(2) at 12 months and the female's BMI was 48.4 kg/m(2) at 28 months, with excess weight loss 58% and 48%, respectively. They developed loose stools associated with eating. These patients have shown a considerable improvement in hypersomnia and respiratory difficulties. BPD proved to be an effective approach to weight loss in PWS, resulting in improvement of sleep apnea, behavior problems and quality of life.
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PMID:Results of biliopancreatic diversion in two patients with Prader-Willi syndrome. 1597 69

In 11 patients with a recessive congenital disorder, which we refer to as "the hypotonia-cystinuria syndrome," microdeletion of part of the SLC3A1 and PREPL genes on chromosome 2p21 was found. Patients present with generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, and failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. Since loss-of-function mutations in SLC3A1 are known to cause isolated cystinuria type I, and since the expression of the flanking genes, C2orf34 and PPM1B, was normal, the extended phenotype can be attributed to the deletion of PREPL. PREPL is localized in the cytosol and shows homology with prolyl endopeptidase and oligopeptidase B. Substitution of the predicted catalytic residues (Ser470, Asp556, and His601) by alanines resulted in loss of reactivity with a serine hydrolase-specific probe. In sharp contrast to prolyl oligopeptidase and oligopeptidase B, which require both aminoterminal and carboxyterminal sequences for activity, PREPL activity appears to depend only on the carboxyterminal domain. Taken together, these results suggest that PREPL is a novel oligopeptidase, with unique structural and functional characteristics, involved in hypotonia-cystinuria syndrome.
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PMID:Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. 1638 48

Monosomy 1p36 is one of the most commonly observed mental retardation (MR) syndromes that results in a clinically recognizable phenotype including delayed psychomotor development and/or MR, hypotonia, epilepsy, hearing loss, growth delay, microcephaly, deep-set eyes, flat nasal bridge and pointed chin. Besides, a Prader-Willi syndrome (PWS)-like phenotype has been described in patients with 1p36 monosomy. Forty-one patients presenting hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who tested negative for PWS were investigated by FISH and/or microsatellite markers. Twenty-six were analyzed with a 1p-specific subtelomeric probe, and one terminal deletion was identified. Thirty patients (15 of which also studied by FISH) were investigated by microsatellite markers, and no interstitial 1p36 deletion was found. Our patient presenting the 1p36 deletion did not have the striking features of this monosomy, but her clinical and behavioral features were quite similar to those observed in patients with PWS, except for the presence of normal sucking at birth. The extent of the deletion could be limited to the most terminal 2.5 Mb of 1p36, within the chromosomal region 1p36.33-1p36.32, that is smaller than usually seen in monosomy 1p36 patients. Therefore, chromosome 1p36.33 deletion should be investigated in patients with hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who test negative for PWS.
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PMID:Prader-Willi-like phenotype: investigation of 1p36 deletion in 41 patients with delayed psychomotor development, hypotonia, obesity and/or hyperphagia, learning disabilities and behavioral problems. 1656 57

The association of obesity, phenotypic abnormalities and mental retardation characterizes syndromic obesity. Its most common form is the Prader-Willi syndrome (PWS-- neonatal hypotonia, poor sucking, delayed psychomotor development, hyperphagia, severe obesity, short stature, small hands and feet, hypogonadism, mild to moderate mental retardation and behavioral disorders). A PWS-like phenotype has been described in patients with chromosome abnormalities involving the chromosome region 6q16.2 that includes the SIM1 gene. Herein we report cytogenetic and gene studies including a screening for the SIM1 gene deletion, performed on 87 patients with PWS-like phenotype, and describe the fifth case of syndromic obesity with an interstitial deletion of the chromosome segment 6q16-q21 and suggest that mutational analysis and further studies of the parental origin of chromosome alterations of 6q16.2 in patients with and without PWS-like phenotype are needed to evaluate possible imprinting effects of SIM1 gene and establish the contribution that alterations in this gene makes to the etiology of syndromic and non-syndromic obesity.
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PMID:A new case of interstitial 6q16.2 deletion in a patient with Prader-Willi-like phenotype and investigation of SIM1 gene deletion in 87 patients with syndromic obesity. 1682 51

The constellation of neonatal hypotonia, developmental delay, hypogonadism and obesity caused by hyperphagia was first reported in 1956 and subsequently termed Prader-Willi syndrome (PWS). Genetic analysis has demonstrated abnormalities of chromosome 15. Anesthesia concerns of PWS include morbid obesity, the potential for difficulties with airway management, risk for perioperative respiratory failure, abnormalities in the central control of ventilation and temperature, rare reports of primary myocardial involvement, aggressive and at times violent behavior and glucose intolerance. For the first time, we report the use of regional anesthesia in four patients with PWS. A lumbar plexus catheter was used to provide postoperative analgesia in one patient while regional anesthesia (fasica iliaca block, spinal anesthesia, and lateral vertical infraclavicular block) was used to provide primary intraoperative anesthesia in three other patients while avoiding the need for general anesthesia. Previous reports of the anesthesia care of patients with PWS are reviewed and the potential perioperative implications of the sequelae of PWS are discussed.
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PMID:Anesthesia and Prader-Willi syndrome: preliminary experience with regional anesthesia. 1687 13

Prader-Willi syndrome is a neurodevelopmental disorder that is characterized by infantile hypotonia, feeding difficulties, hypogonadism, mental deficiency, hyperphagia (leading to obesity in early childhood), learning problems, and behavioral difficulties. A paternal 15q11-q13 deletion is found in approximately 70% of patients with Prader-Willi syndrome, approximately 25% have uniparental maternal disomy 15, and the remaining 2% to 5% have imprinting defects. The proximal deletion breakpoint in the 15q11-q13 region occurs at 1 of 2 sites located within either of 2 large duplicons allowing for the identification of 2 deletion subgroups. The larger, type I (TI) deletion involves breakpoint 1, which is close to the centromere, whereas the smaller, type II (TII) deletion involves breakpoint 2, located approximately 500 kilobases distal to breakpoint 1. Breakpoint 3 is located at the distal end of the 15q11-q13 region and common to both typical deletion subgroups. Analyses of the genetic subtypes of Prader-Willi syndrome to date have primarily compared individuals with typical deletion and uniparental maternal disomy 15 without grouping the individuals with a deletion into TI or TII. Distinct differences have been reported between individuals with Prader-Willi syndrome resulting from deletion compared with uniparental maternal disomy 15 in physical, cognitive, and behavioral parameters. We previously presented the first assessment of clinical differences in individuals with Prader-Willi syndrome categorized as having type I or II deletions. Adaptive behavior, obsessive-compulsive behaviors, reading, math, and visual-motor integration assessments were generally poorer in individuals with Prader-Willi syndrome and the TI deletion compared with subjects with Prader-Willi syndrome with the TII deletion or uniparental maternal disomy 15. Four genes (NIPA1, NIPA2, CYFIP1, and GCP5) have been identified in the chromosomal region between breakpoints 1 and 2 and are implicated in compulsive behavior and lower intellectual ability observed in individuals with Prader-Willi syndrome with TI versus TII deletions. We quantified messenger-RNA levels of these 4 genes in actively growing lymphoblastoid cells derived from 8 subjects with Prader-Willi syndrome with the TI deletion (4 males, 4 females; mean: age 25.2 +/- 8.9 years) and 9 with the TII deletion (3 males, 6 females; mean age: 19.5 +/- 5.8 years). Messenger-RNA levels were correlated with validated psychological and behavioral scales administered by trained psychologists blinded to genotype status. Messenger RNA from NIPA1, NIPA2, CYFIP1, and GCP5 was reduced but detectable in the subjects with Prader-Willi syndrome with the TI deletion, supporting biallelic expression. For the most part, messenger-RNA values were positively correlated with assessment parameters, indicating a direct relationship between messenger-RNA levels and better assessment scores, with the highest correlation for NIPA2. The coefficient of determination indicated the quantity of messenger RNA of the 4 genes explained from 24% to 99% of the variation of the behavioral and academic parameters measured. By comparison, the coefficient of determination for deletion type alone explained 5% to 50% of the variation in the assessed parameters. Understanding the influence of gene expression on behavioral and cognitive characteristics in humans is in the early stage of research development. Additional research is needed to identify the function of these genes and their interaction with gene networks to clarify the potential role they play in central nervous system development and function.
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PMID:Expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in Prader-Willi syndrome. 1698 6


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