Saturday, 31 August 2013

8th International PWS Conference in Cambridge

8th International PWS Organisation Conference
Jackie Waters


With grateful thanks to Dr Suzanne B Cassidy for checking and amending the original draft and to Dr June-Anne Gold for her additional comments

PWSA UK had been preparing for three years to host the 8th International PWS Organisation Conference.  It was not an easy process, not least when the venue we had booked to host the Celebration Supper/Gala Dinner was burned to the ground by arsonists just a year before the conference was due to take place. 

The conference was, however, voted a great success by those who attended. It was split into three programmes: scientific, caregivers (for those working in residential care and supported living), and parents. The parents programme was then split into three for parents of children under 5, 6-16 and 16+. 

The following report gives some of the main highlights from the scientific programme (many of the talks in the parent programme were on similar subjects) but it is impossible to cover all the talks and poster presentations within the context of this article. If you would like to know more, some of the presentations and the abstract book are available to view online at – click on the link on the home page.

You can also order a hard copy of the abstract/programme book (while stocks last) for the cost of postage (£2 in the UK). If you’d like a copy, please contact Maggie Rowley at our office address, or email
PWS in the wider context
Guest speaker, Stephen O’Rahilly, Professor of Clinical Biochemistry and Medicine at the University of Cambridge Metabolic Research Laboratories, put PWS into the wider context of obesity research, in that much can be learned about how bodies control fat stores and nutrient levels through studying those where these processes have gone awry, such as people with PWS.  He highlighted the fact that, for the first time in human evolution, humanity is consuming surplus energy to that which it is expending, hence the “obesity epidemic”. However, recent studies have shown that up to 70% of the difference between lean and obese people can be traced to genetic or hereditary factors. Most of the genes which have been identified in “normal” obese people are expressed in the hypothalamus. 

Prevalence, birth incidence and mortality rates
There have been many estimates over the years as to the prevalence and birth incidence of PWS. Tess Lionti and her team from Murdoch Children’s Research Institute in Australia looked at 156 Australians with PWS and found a birth incidence of 1:14,000 and a prevalence of between 1:25,000 and 1:29,000. They found that at 35 years of age, 87% of people with PWS were still living, compared with 98% in the general population. They also reported that generally obesity increased with age, and this remains the major cause of early death. Non-obese people had better survival.

Changing clinical perspectives
Daniel J Driscoll, from the University of Florida, USA, spoke about interventions and changing clinical perspectives in PWS. He commented that PWS was the first recognized human disorder related to genomic imprinting (differences in gene expression depending on the parent from whom the gene was inherited). He went on to say that the previous two-stage model of PWS (pre- and post-hyperphagia) had now been replaced by a model, based on longitudinal studies, of 7 distinct nutritional phases (described by Miller at al, Journal of Medical Genetics, 2011), indicating that PWS is more complex than originally thought.

Dr Miller’s published article describes these phases thus:
“Phase 0 occurs in utero, with decreased fetal movements and growth restriction compared to unaffected siblings.
Phase 1 the infant is hypotonic and not obese, with sub-phase 1a characterized by difficulty feeding with or without failure to thrive (ages birth—15 months; median age at completion: 9 months). This phase is followed by sub-phase 1b when the infant grows steadily along a growth curve and weight is increasing at a normal rate (median age of onset: 9 months; age quartiles 5–15 months).
Phase 2 is associated with weight gain—in sub-phase 2a the weight increases without a significant change in appetite or caloric intake (median age of onset 2.08 years; age quartiles 20–31 months;), while in sub-phase 2b the weight gain is associated with a concomitant increased interest in food (median age of onset: 4.5 years; quartiles 3–5.25 years).
Phase 3 is characterized by hyperphagia, typically accompanied by food-seeking and lack of satiety (median age of onset: 8 years; quartiles 5–13 years). Some adults progress to:
Phase 4 which is when an individual who was previously in phase 3 no longer has an insatiable appetite and is able to feel full.
Dr. Driscoll also described a number of ongoing PWS clinical research and drug trials. 

In his talk Bernhard Horsthemke, from the Institut für Humagenetik in Germamy, described how finding a microdeletion affecting the SNORD116 snoRNA gene cluster in a few patients pointed to a major role of this gene in PWS. This is one of the genes located in the region of chromosome 15 relevant to the cause of PWS. But he also warned that, despite many years research, it is still unclear how or what roles this gene actually plays in causing the features of PWS. Although mouse models have been used extensively in trying to understand PWS, they are not an exact or ideal match. For instance, human lipid metabolism and obesity is not replicated in mouse models, their immune system is different, and they do not have cholesterol. There is still no mouse model of PWS which is obese.

SNORD116 and the regulation of energy homeostasis in PWS
More research into SNORD116 was included in a poster presentation by a team at the Garvan Institute of Medical Research in Australia. They generated mouse models which were lacking in the SNORD116 gene and investigated their metabolic physiology. They found that these mice suffered growth deficiency from birth, with reduced body weight, bone mass and length, compared with healthy mice. They also showed increased food intake and an impairment in the growth hormone pathway.
Marc Lalande, from University of Connecticut, presented work on the development and use of pluripotent stem cells to study the mechanism of silencing and re-activating of the maternally inherited genes related to PWS, especially SNORD116. Once this is understood, there is the potential for future treatments by reactivating these genes.
Françoise Muscatelli presented work from researchers in France that showed a small amount of residual expression from imprinted genes, especially NDN, in the PWS region, and they were able to show better outcomes in mice with higher residual function. Re-activating imprinted genes to improve outcomes in PWS may be able to be exploited. 

Endocrinology and hyperphagia
A talk by Anthony Goldstone, of Imperial College London, outlined the extensive role that neuroendocrine factors have in PWS. These include underdeveloped genitalia, childhood development of obesity and hyperphagia (excessive eating), growth hormone deficiency, delayed puberty and infertility (in most), developmental delay and learning disabilities, and abnormal sleep patterns. Dr Goldstone reported that people with PWS have normal fasting and post-prandial (after meal) plasma levels of several anorexigenic (appetite suppressing) hormones (leptin, PYY, GLP-1 and CCK). However, fasting and post-prandial levels of the anorexigenic hormone pancreatic polypeptide (PP) are reduced in PWS, and this appears to be present from early childhood. As with genetics, there is still much research to be done. The cause for the delayed development of hyperphagia remains unknown and, in addition to hormonal abnormalities, there are likely to be overriding hypothalamic brain defects which also contribute to the appetite problems. 

Indian cactus caralluma fimbriata – effect on hyperphagia
A small scale study of the use of caralluma fimbriata extract (CFE), a cactus extract, was performed by Joanne Griggs and her team at the Victoria University College of Health Biomedicine in Australia. Nine children and adolescents aged between 5 and 17 years were given powdered CFE or a placebo. Interim results suggested that supplementation with CFE decreases appetite behaviour in some children and adolescents with PWS and some decrease in behaviours relating to distraction and distress. They are now hoping to extend their research into a worldwide population to see if these results are replicated in a larger sample of patients. CFE is licensed for use as “Slimaluma”. There was no monitoring of liver function tests during this study.

Vagus nerve stimulation in PWS: effects on eating and behaviour
A team from the Department of Psychiatry at the University of Cambridge presented a poster about three individuals with PWS who underwent surgery to implant a vagus nerve stimulation (VNS) device. This device is used to control epilepsy, but it had been noted that these patients with epilepsy also lost weight.  The team wanted to test the theory that this would also occur with PWS patients.  Effects on weight were equivocal, with one person putting on weight and others showing some improvement in eating behaviour.  However, unexpectedly, two of the three participants reported marked improvements in their behaviour and asked for the VNS to continue at the end of the study.

Thyroid function in children and adolescents with PWS
In a poster presentation, a team from Italy had conducted thyroid function tests on 299 children and adolescents with genetically confirmed PWS, and found thyroid axis dysfunction in 10.7% of their patients – more than is in the general population. They conclude that thyroid function should be carefully evaluated in PWS patients to identify those who may require hormonal replacement therapy.

Assessment of adrenal function
A poster presentation by a Japanese team from Dokkyo Medical University set out to assess adrenal function in 36 children and adolescents with PWS by insulin tolerance test. Central adrenal insufficiency (CAI) due to hypothalamic dysfunction had previously been suggested as a possible cause of death by other researchers, particularly in association with infection-related stress. This study results suggest that basal and peak levels of cortisol are within the normal range in PWS patients, while peak responses of cortisol to insulin stimulation are delayed in most patients. The researchers state that it is likely that hypothalamic dysfunction alters secretion patterns of cortisol in PWS, but say that further studies are necessary to clarify the possible association between the altered response of cortisol to hypoglycaemia and unexplained deaths in PWS.

In her talk on New Perspectives for Prader-Willi Syndrome, Maithé Tauber, of the Centre de Référence du Syndrome de Prader-Willi in France, acknowledged that the cure for PWS remains the foremost issue for persons with PWS and their families and carers. She described how her team’s research into oxytocin administered to 24 adult patients with PWS showed a positive effect on trust in others and on disruptive behaviour, with a trend towards decreased food intake. In PWS mouse models, they demonstrated that a single injection of oxytocin in the first five hours of life completely rescued the newborn mice from early death by recovering normal suckling abilities. They are now testing this treatment with 5 babies with PWS, and long term effects are currently being analysed, with the hope that this may offer positive treatment early in life.

However, a different result of treatment with oxytocin was reported by Ellie Smith, University of Sydney, Australia, who described her team’s research in administering oxytocin or a placebo as a nasal spray to 31 people with PWS aged between 12 and 30 years. Behaviours such as hyperphagia, temper outbursts, skin-picking, obsessive behaviours, and under-reaction to pain were evaluated daily by primary carers. The outcomes were disappointing in that there were no significant differences between those who received oxytocin and those who received the placebo.

Growth hormone treatment in children
Nienke Bakker, from the Dutch Growth Research Foundation in Rotterdam, reported on 8 years of growth hormone (GH) treatment in 60 children with PWS. The Dutch team found that during this time lean body mass improved, fat percentage and body mass index remained stable, while height and head circumference had completely normalised. They conclude that GH is a potent force for counteracting the clinical course of obesity in PWS. 

Growth hormone and face shape
Using dense surface modelling and shape signature techniques, Peter Hammond and teams from University College London and the University of Catania, Italy, demonstrated that growth hormone therapy in PWS has a corrective effect on vertical facial growth, but not more generally on face shape.

Effect of growth hormone on bone fragility and effect on BMI and adipose tissue of stopping growth hormone
In a poster presentation, a team from the Dokkyo Medical University, Japan, investigated 148 patients (112 treated with GH and 36 untreated) between 2 and 47 years of age to assess bone mineral density (BMD) in the lumbar spine (L2-4). They also looked at scoliosis, which was present in 45 treated and 19 untreated patients. They found that 33.8% of the patients had BMD below the normal range (osteoporosis), and 27.7% had low normal BMD (osteopenia). The difference in BMD between those with and without scoliosis did not reach statistical significance.  Treatment with GH did improve BMD. They suggest that GH may be a useful treatment for reducing the frequency of bone fractures and surgical complications caused by osteoporosis.

In a separate poster, this research team also looked at 14 patients with PWS before and after the cessation of GH treatment. They discovered that body mass index (BMI) significantly increased after cessation, though subcutaneous and visceral adipose tissue was not significantly affected. They conclude that to maintain good body composition and prevent complications of obesity, long-term use of GH in adult patients with PWS may be advisable. 

Growth hormone therapy and respiratory disorders: long-term follow-up in PWS children
In another poster presentation, a team from Italy looked at the effects of long-term growth hormone therapy on sleep-disordered breathing and adenotonsillar hypertrophy in 50 children with PWS.  They observed an increase of apnoea hypopnoea and a decrease of central apnoea events, leading to an overall decrease of the respiratory disturbance index.  However, the percentage of patients with severe adenotonsillar hypertrophy increased significantly after two and three years of growth hormone treatment. They recommend annual overnight polysomnography checks and adenotonsillar evaluation.

Another poster presentation on this topic was from a Scandinavian collaborative group. These authors conducted a placebo controlled study of GH in 46 adults with PWS that respiratory polysomnography did not change over time with GH treatment, and therefore that GH in PWS is not associated with increased risk of sleep apnea.

Sex hormone deficiency
The Hypothalamic-Pituitory –Gonadal (HPG) Axis is Active in Prader-Willi syndrome infants
Harry Hirsch, of The Hebrew University, Israel, reported on research his team had conducted into hypogonadism (immature sexual development) in infants with PWS. As nearly all adult men with PWS have abnormally low testosterone levels and adult females have low Inhibin B levels (a hormone produced by ovarian follicles), it might be expected to find abnormally low levels of these reproductive hormones in infants with PWS. Normal infants have an increase in the HPG axis from birth to 4 months often referred to as “minipuberty”. However, of the 9 male and 6 female infants with PWS the Israeli team studied, all of the boys and some of the girls had normal reproductive hormone levels for age. These results show that most infants with PWS are not born with deficiencies in sex hormone production, and that further studies are needed to determine why gonadal function becomes abnormal in PWS adolescents and adults and why genitalia are small starting at birth.

Pregnancy in PWS
Two new cases of women with deletion-type PWS becoming pregnant were described by Suzanne Cassidy, from the University of California. One case was a 27 year old woman who had a normal son, delivered by Caesarean section. She had had no psychotropic medications. The other case was a 31 year old woman who took Citalopram for two years before pregnancy. Her daughter had Angelman syndrome. There have been two previously reported cases of successful pregnancy to women with PWS. Dr Cassidy concluded that fertility in a few women with PWS probably reflects variability in hypogonadism and absence of opportunity in others who are potentially fertile, and recommends that sex education and contraception should be part of the management of women with PWS.

Treatment of Hypogonadism in Females
In a poster, Talia Eldar-Geva presented the Israeli group’s approach to treating hypogonadism in adolescent and adult females with PWS. Their approach is individualized, using contraception and hormone replacement based on bone density, hormonal profiles and personal and family wishes.

The topic of scoliosis and other spinal deformities in PWS was addressed by Harold van Bosse, of the Shriners Hospital for Children, Pennsylvania. He said that 40-90% of children with PWS have spinal deformities, and that 15% of all children will require treatment. There are two main peaks in incidence of scoliosis 0-24 months representing initial hypotonia and the second being idiopathic. His data did not support discontinuing growth hormone treatment, and in fact indicated that its use correlated with decreased risk for spine surgery.
In a poster presentation, Dr van Bosse discussed the prevention of surgical complications in PWS scoliosis surgery. Previous studies had reported frequent serious complications after spinal procedures, with rates as high as 56%. He and his team developed a protocol for pre-operative work-up and peri-operative care to minimize complications. The pre-operative protocol included pulmonary function tests, sleep studies, and assessments for behavioural risks. Surgical planning avoided anterior approached, and paid special attention to the characteristic osteopenia and cervicothoracic kyphosis of PWS. Post surgery, extubation was delayed, followed by BiPAP or CPAP. Oral intake was delayed. He concludes that scoliosis surgery can be performed safely in children with PWS, as long as there is careful attention to their special physiological and emotional characteristics. 

General anaesthesia
The topic of general anaesthetics has always been one of concern to parents and Graziano Grugni, of S Andrea Hospital, Vercelli, Italy, described his team’s survey of 49 patients with PWS who had, in total, 101 surgical episodes, programmed in 95 cases, and as an emergency in 6. Of these, only four patients reported problems after general anaesthesia, two with respiratory insufficiency and two with psychomotor agitation. The researchers concluded that no complication leading to lasting disability or death had been observed.

Nutrition in children with PWS
Chris Smith, who is the dietitian attached to the PWS Multidisciplinary Clinic at Brighton and Sussex University Hospitals Trust, reported on an analysis of food diaries kept by 11 parents of children with PWS over 10 years. His team found that PWS children on average have 30% less calorific intake, compared to other children of the same age. The proportions of % energy from fat, carbohydrate and protein (compared to UK recommendations) were 25% (35%), 59% (50%) and 16% (15%) respectively. The lower fat intake meant that children were at increased risk of inadequate intake of polyunsaturated fats, but there appeared to be little detrimental effect on micronutrient intake overall. 

Post-prandial metabolic profile in adults with PWS
This study by Louise Purtell and her team at The Children’s Hospital, Sydney, Australia, set out to investigate the basis behind the development of obesity in PWS, and especially why even those who are on a closely controlled calorie-restricted diet still become obese. They hypothesized that this may be due to the way people with PWS metabolise energy after eating a meal, but their study found there were no differences in measures of meal metabolism between those with PWS and non-PWS obese people when the amount of lean body mass was taken into account. The study did not detect an intrinsic metabolic problem in people with PWS and suggested that the development of obesity in PWS, even on a strict diet, may be due to other factors.

A poster presentation by Elena Borgova from Russia showed significantly higher levels of Brain Derived Neurotrophic Factor (BDBF) over two control groups of non-PWS obese individuals and lean controls. Brain-derived neurotrophic factor (BDNF) is a neurotrophin, known to affect neuron maintenance or function, and it also contributes to the central control of food intake. 

Dr Bogova’s study suggests possible resistance to BDNF at its receptor in individuals with PWS. BDNF signaling in PWS needs to be full defined and may lead to new treatment strategies.  

GLP-1 based therapies (Liraglutide and Exenatide) – effect on weight loss and stomach emptying
Anthony Goldstone’s team at Imperial College London looked at the potential for using drugs such as Liraglutide and Exenatide, normally used for treating diabetes, in stimulating insulin release and weight loss in people with PWS. However, there had been theoretical concerns about the safety of using these drugs in PWS because they are known to cause delayed stomach emptying, already known to be a potentially fatal issue in PWS because of the risk of stomach rupture. While Liraglutide improved sugar control, it did not have a major impact on hyperphagia or weight gain other than helping to prevent weight gain related to the use of insulin. The team therefore advises caution in the use of these drugs.
Very similar results were obtain in another study of GLP-1 treatment in PWS presented by the Italian collaborative endocrine group.

Pain and PWS
The Italian collaborative group presented a study investigating the cause of the high pain threshold in PWS in 11 adults with PWS, 3 obese non-diabetic people and 7 age-matched normal weight healthy adults, using nerve conduction and somatosensory evoked potential studies, quantitative sensory testing, quantitative insulin-sensitivity, and a skin biopsy. They found normal electroneurographic studies, but significantly higher thermal and pain thresholds and reduced proximal and distal intraepidermal nerve fibres in PWS. They conclude that altered perceptions of pain in PWS are mainly based on loss of sensory neurons in dorsal root ganglia.

Infection and PWS
In a poster, the Italian collaborative group presented a study that looked at the risk of infection in 116 people with PWS compared with 113 normal subjects matched for age, gender and environment. No difference between the two groups was found despite the fact that there were more surgical procedures in the PWS group. However, the PWS group showed more lower respiratory severe infections, though fewer mild infections, possibly related to high threshold of pain and vomiting.

Cognition – Executive functioning
Johann Chevalere‘s  team from Université Bordeaux, Segalen, France suggested from two studies that executive functioning in PWS is impaired and that the impairment is highly connected with the intellectual disability. Differences were found between the deletion and the m-UPD groups for the two task assessing, planning and mental switching, the m-UPD performing worse than the deletion group. However the deficit on switching and cognitive estimation is not totally attributable to intellectual level, suggesting syndrome-specific association. Executive function seems to vary with the genotype.

The team from the Cerebra Centre in Birmingham, UK, demonstrated that changing routines triggered more temper behaviours. They found that signalling any potential changes in advance by showing a card to the person with PWS triggered less temper outbursts, and they also recommended more research into increasing the flexibility of routines from an early age as a potential helpful management technique.
A Dutch group studied 66 children with PWS using several different tests of social cognitive functioning and showed a markedly reduced level of social cognitive ability, suggesting that the approach to them should be adjusted accordingly.

Brain abnormalities between different genetic subtypes
Akvile Lukoshe and the team from the Dutch Growth Research Foundation investigated global brain morphology in children with PWS, using MRI imaging and comparing the different genetic subtypes of deletion (DEL) and maternal uniparental disomy (mUPD). They found that both subtypes show signs of impaired brain growth indicated by smaller cortical surface area and smaller global white matter volume. However, children with mUPD also show signs of early brain atrophy and increased cortical thickness, similar to that found in autism. In contrast, children with DEL have a proportionately developed, albeit smaller brain compared to healthy age matched sibling controls. They suggest that the results show divergent neurodevelopmental patterns in children with DEL and mUPD.

Autism spectrum disorders
Symptoms of autism spectrum disorders in children with PWS
In a poster presentation the team from the Dutch Growth Research Foundation and Erasmus University, Rotterdam, tested 66 children aged 7 to 17 years using the Theory of Mind Test-R (ToM) and the Diagnostic Interview for Social Communication Disorders. ToM includes the ability to share feelings of others (empathy). ToM development was related to IQ levels, but not to genetic sub-type, and one third of the children scored positive for Autism Spectrum Disorder. The team highlighted the importance of an adjusted approach to children with PWS. Their impaired empathetic abilities require clear communication such as avoidance of figurative language and naming things precisely.
A study contacted by researchers from Dokkyo Medical University, Japan, looked at 45 Japanese individuals with PWS. Their findings were consistent with previous studies on Caucasian patients, and indicated that those with mUPD were more prone to autism spectrum disorders, regardless of ethnicity. These were less apparent in childhood.

Psychotic illness
Researchers at the Maastricht University Medical Centre reviewed literature relating to psychosis in PWS. Overall, in a total of 602 reported individuals, they found that psychotic illness is more prevalent among those with disomy (mUPD) (15.6%) than those with a deletion (8.8%).
In a poster, Denise Thuilleaux presented results from a French-Spanish collaborative psychopathological profile study of 154 adults with PWS. They found basal (49%), impulsive (24%), compulsive (16%) and psychotic profiles. Overall, 11% had psychosis, but those with UPD had a 25% prevalence of psychosis.
Tony Holland, PWSA UK President, from the University of Cambridge proposed a clinical trial to investigate whether psychosis can be prevented in PWS. This was based on the case of an older adult with mUPD who had not become psychotic, but who had been given antipsychotic medication to control behaviour problems earlier in his life. It has also been noted that antipsychotic medication was very effective where cases did occur, and relapse rates appeared to have been less in those who continued the medication after recovery. They proposed to recruit people with mUPD aged 16 to 20 years who had never had a psychotic illness, allocating them to an experimental or a control group. Those in the experimental group would be given low doses of antipsychotic medication. Tony asked if this could be an international study, but also if such a study was appropriate or ethically justified.

Monday, 26 August 2013

Water Intoxication in PWS

Due to medical crisis where a young person with PWS ended up in intensive care with a possible diagnosis of water intoxication, we have asked our medical boards about the situation and the following is a compilation from their responses.

Water intoxication is well known to occur in children and adults with eating disorders regardless of mental abilities, and also in individuals who are severely retarded. This is not a new phenomenon.  The problem of water intoxication is a difficult one and may be related to two different physiological mechanisms: some of the patients we have seen have compulsive water drinking and often need to be restricted and / or monitored in order to keep their electrolytes in balance; this seems to be a problem related to the PWS itself. 

On the other hand there is a syndrome called SIADH (Syndrome of Inappropriate Antidiruetic Hormone Hypersecretion) which is related to a problem the kidney has in filtering out the excretions and in this case the kidney absorbs too much water. This problem may be related to medications, may occur with other psychiatric maladies and may occur unrelated to all of these. The latter problem is much more likely to throw the electrolytes out of order, as the body usually seems designed to handle fluids without throwing electrolytes off. However with the person with PWS, this may be more complicated because of right heart failure, and decidedly needs to be reviewed and handled by a pediatrician/internist.

In SIADH, there is an inappropriate release of anti-diuretic hormone that causes water retention and can cause a severe hyponatremia (metabolic condition in which there is not enough sodium (salt) in the body fluids outside the cells).  What medications the individual is on, or if there were other medical issues, may make a difference for the diagnosis of water intoxication. Although this is not a common happening in PWS, it pays to be aware that it has happened in a few cases. 

Symptoms of hyponatremia include: Common symptoms include: 

Abnormal mental status:
  • Confusion
  • Decreased consciousness
  • Hallucinations
  • Possible coma
  • Convulsions
  • Fatigue
  • Headache
  • Irritability
  • Loss of appetite
  • Muscle spasms or cramps
  • Muscle weakness
  • Nausea
  • Restlessness
  • Vomiting
A further study done on 45 individuals with PWS also found: " In 45 the clinical PWS diagnosis was confirmed by molecular (genetic) testing: nine of them with a confirmed PWS diagnosis had a deletion of chromosome 15q11-13, in nine individuals no deletion was identified. The majority of individuals who increased their water consumption to extreme values belonged to the non-deletion group. Two in the non-deletion group developed hyponatraemia while receiving psychiatric medication."

Treatment seems to be by administering desmopressin  (a hormone used to reduce urine production) either orally, or nasally.

Physicians, see also: 

Water intoxication in a patient with the Prader-Willi syndrome treated with desmopressin for nocturnal enuresis.