NEWS ABOUT PRADER-WILLI SYNDROME

CLINICAL RESEARCH
PRESENTED
at the IPWSO conference in Taiwan, May 2010
ZALAU.October.2010
Susanne Blichfeldt
Denmark
 PWS the first days and weeks
• The newborn: Apgar score is often normal, and
the hypotonia is not always remarked at birth,
but after some hours or days
• During the first days the child becomes
increasingly sleepy, show no interest in food and
sleeps most of the time. Why ?
• Tube feeding most often needed for a period
• After the first months:
• the child becomes more alert, eats better.
 PWS stages related to appetite
• 1a: o-9 months: hypotonia, feeding problems
• 1b: 9-25 months: appetite seems normal
• 2a: 2-4 years: appetite seems normal ?
• But weight goes up!
• 2b: 4-5 years: increasing appetite
• 3: after age 3-5 years: great interest for food,
risk of hyperphagia and severe overweight.
• 4: Less appetite and food seeking after 30 years
 PWS stages related to weight
• 15 % low birth weight compared with family
• 0 – 6 month: low weight & feeding problems
• 6 – 18 month:weight goes up, eat normal food
• After age 18 months : great differences in weight
and calorie needs .
• Individual evaluation important
• Weight becomes more stable after 30 years?
 PWS and GHRELIN
• Ghrelin is elevated in PWS from young age
• The reason is unknown
• Ghrelin reflects appetite, also the wish to eat?

• Ghrelin levels seems to fall when you are aware

that the meal is over!
• Grelin reflects the expectation of food ?
• More research is needed
 PWS: BMI and body composition
• In PWS the lean body mass is small
• BMI (kg/m2) does not tell how much fat the body
contains, a DEXA scan is more precise
• 70 kg weight: 60/10 or 40/30 of lean/fat ratio?
• The amount of lean body mass determines the
calorie needs.
• In PWS: The lean body mass becomes bigger
with growth hormone treatment.
 PWS and calorie needs
• Depends on body size, lean body mass
and physical activity.
• Calorie needs for growth are very small
after the first year of life

• Small lean body mass, physical inactivity

means very low calorie needs.
• Examples of calorie use in activties:
 PWS and metabolic syndrome
• Metabolic syndrome is caused by obesity and
comprises 2 of the following symptoms:
• Fat on inner organs in the body
• Hypertension
• Atherosclerosis
• Type ll diabetes mellitus
• Elevated cholesterole
• 70% of overweight persons with PWS have MS
 Fitness and home exercises
• Australia: 26 adults with PWS:
• 2 groups both recommended daily physical
activity of 15-40 min:

• Group l: Fitness “ machines” at home had an

average weight loss of 9kg (+/- 5 kg)
• Group II: No machines: had an average weight
gain of 2 kg +/-4,2)
 PWS and teeth and reflux
• Enamel problems are seen in all ages
• The teeth are often worn down
• Poor tooth hygiene often seen in adults
• Caries more often in adults than in children !
saliva: can be stimulated with chewing gum
Reflux from the stomach: often not diagnosed, but
is seen in the teeth. Reflux can be treated.
Take care of coca cola, also diet products
 PWS and scolioses
• Japan: 40 % of PWS. 25 % are operated (10%)
• Less complications than before.
• Growth hormone treatment after operation gives
a better prognosis
• USA:
16% of 0-6 years old, 46% after 18 years of age
17% : brace, 13% operated,
22% brace and then operation
 PWS and orthopaedic problems
• Australia:
• Children: 70% flat-footed
• 10% hip dislocation
• 37% scolioses

• Genu valgus, instability of ankle joints,

• Rememer to look at feet and shoes !
 PWS and the hormonal system
• Growth hormone
• Thyroid hormone
• Adrenal hormone
• Sex steroids
 Growth Hormone:France
• 80-85% have GHD. All profit of tretament
• Children:
• better motor performance, and bigger head !
• Adults:
• bigger muscles and bone, less fat
• Too high doses of GH gives acromegalic traits
• GH doses must be carefully adjusted, based on
IGF-1 levels. Blood sugar measures regularly!
 Growth hormone adults: DK-N-S
• 46 adults: first placebo controlled study of
growth hormone treatment during in 3 years in
adults with PWS.
• 23 got placebo the first year.

• Body fat decreased 2-4 kg after one year and

lean body mass increased 2-3kg.
No more changes during 2.year.
• No side effects
 Thyroid function
• France: up to 24 % need treatment

• Important to check thyroid function regularly

• Previously it has been reported that low thyroid

function is rare in PWS, but it seems to be rather
common
 Adrenal function
• In 2008 was reported (Dutsch study) that 15 of
25 had an insufficient adrenal cortisol response
to an over-night methyrapone test

• Presentations in Taiwan:
• Standard synachten test in 57 Danish/Swedish
children and adults showed normal values in 53,
later insulin tolerance test was normal in the 4
• Italian study:36 of 38 had normal synachten test.
 Hypogoadism
• Primary or secondary

• In PWS there seems to be a combination:

• Both primary gonadal defect and secondary

hypogonadism due to hypothalamic dysfuncton
and (most often) combinations of both can be
seen
 Sex steroids and treatment. Japan
• Testosterone treatment of males with PWS :
• 125 mg depot i.m. monthly
• No behavioural problems
• Increasing beard and pigmentation
• Lean body mass improved
• Self confidence improved
• Coclusion:
• Testosterone is a safe treatment in PWS!
 PWS and incontinense
• The Netherlands:

• 13 % of older children and adults are incontinent

during night (nocturnal enuresis)
• 4 % during day time
• 3 % have fecal incontinence (constipation?)
 Aging in PWS: in the Netherlands
• 102 persons : 18-66 years:
• 54%deletion, 45% UPD, 3% IM
• 56% BMI > 30. 17% DM
• 9% hypertension 5% stroke
• 56% leg edema 38% leg ulcers with infection
• 16% osteporoses ( or more?)
• 38 % constipation
• 38% psychiatric diseases or episodes
 Focus on research in PWS
• Clinical investigations
• Mouse models
• Energy balance in PWS
• Genetics

• Psychyatric diseases
 Actual clinical research focus(USA)

• Hypotonia in infancy : Why

• Appetite regulation: How

• Adrenal insufficiency: need of treatment ?

• Autonome dysfunction: how and why