The Montreal Children's Hospital
Hyperphenylalaninemia (PKU) Resource Booklet
Created by Peter M. Nowacki at The Biochemical
Genetics Unit; updated by Annie Capua, Margaret Lilly, David Côté, Manyphong
Phommarinh and Shannon Ryan
Why this text exists
|This text is written as a source of information and explanation for
individuals and families living with phenylketonuria, as well as for
students of all kinds seeking information. In most cases PKU and related
forms of hyperphenylalaninemia (HPA) are diagnosed following routine
newborn screening. New parents are notified of the diagnosis and are given
an explanation about the condition and how it is treated. Understandably,
many people find it very challenging to retain all of this troubling new
information at a first session with a doctor or counsellor. This document
has thus been prepared by the staff at the Biochemical Genetics Unit of
The Montreal Children's Hospital to expand on this information. If you
find that after reading this booklet you still have unanswered questions,
please do not hesitate to contact us. It is very important that parents,
and other relatives who are involved with the affected child, understand
the nature of this condition, as they are effectively the ones who are
administering the treatment under the guidance of the doctor and
photo was taken at my wedding a few years ago. I have PKU. I was
diagnosed on the 3rd day of my life when treatment with the diet
began. I stayed on the diet for 16 years. After I married and when
my husband and I decided we would like to have a child, I went back
on the diet before conception and I stayed on it throughout the
pregnancy. Our daughter Stephanie was born without any evidence of
maternal PKU effects. She is now in her second year and passing all
her developmental milestones in style. The other woman in the
picture is my older sister. She also has PKU but when she was born
there was no newborn screening program for PKU. The diagnosis of her
disease was made late in her first year of life when she developed
convulsions. It was too late for treatment and she has never known
the benefits of early diagnosis and treatment as I know them. Our
picture is on this web site so that parents of newly-diagnosed
infants with PKU will have some evidence of good news. (Irene, May 1998)
The girl in this picture is
Stephanie, age 2 years, daughter of Irene (the bride in the wedding
photo). Irene and her husband planned the pregnancy; dietary control
was excellent from conception to delivery. The hazards of maternal
hyperphenylalaninemia were avoided. Stephanie has passed all
developmental milestones with distinction.
About Us :
Dr. Charles R. Scriver, Former Director, and PAHdb Curator
Manyphong Phommarinh, Programmer and PAHdb Curator
Marie Lefrançois, Dietitian
Shannon Ryan, Technician
Lynne Prevost, Secretary: (514) 412-4417
Fax: (514) 412-4329
How to Contact us :
Biochemical Genetics Unit
Montreal Children's Hospital, Room A-718
2300 Tupper St., Montreal, Quebec, H3H 1P3
Fax: (514) 412-4329
material was compiled by...
Peter M. Nowacki
Dr. Eileen Treacy
Dr. Charles R. Scriver
Should an emergency occur, immediately inform the attending doctor that
your child is affected with PKU.
This brief list of terms has been included here to assist you in
understanding the information contained in this booklet.
- Amino Acid
- The basic building block of proteins. Phenylalanine is an amino
- An unaffected person (a heterozygote) who has one abnormal variant
phenylalanine hydroxylase (PAH) gene, and one normal PAH
- Structures on which genes are found. There are 46 nuclear
chromosomes in each cell of the body (23 pairs). One member of each
nuclear pair comes from the mother's egg and the other from the
father's sperm. The PKU gene is on chromosome 12 (long arm, q; band
- Congenital heart disease
- A heart malformation that is present at birth.
- A substance produced by living cells that promotes chemical
change. An enzyme increases the rate at which one metabolite is
transformed into another. The Phenylalanine hydroxylase (PAH)
protein is an enzyme.
- Units of heredity, or a digital information code embedded in the
DNA molecule. Genes are arranged in sequence on structures called
chromosomes which are found in the nuclei of our cells. There are
approximately 30 000 genes passed on from parent to child. Genes are
encoded instructions for the normal development of our bodies and
the daily functions of our cells.
- Guthrie Test
- A blood test that measures the quantity of phenylalanine in the
blood. This common test is used for screening newborns for PKU and
other forms of hyperphenylalaninemia.
- Hyperphenylalaninemia (HPA)
- A term which implies higher than normal PHE levels in body fluids.
This term encompasses PKU, milder forms of PKU, as well as those
forms of HPA caused by the impaired synthesis and recycling of the
cofactor (BH4) which enable PAH to
convert PHE to TYR.
- Inheritance / heredity
- The process by which biological traits are passed from parents to
- Maternal PKU
- A condition in which the developing fetus of a woman who has
inherited PKU is subjected to the mother's elevated blood PHE level.
Such a level of PHE can harm the fetus even if this fetus has not
inherited PKU from his or her parents. Thus, it is essential for
expecting mothers who have hyperphenylalaninemia to be on a strictly
controlled PHE restricted diet to avoid harming their fetus.
- Metabolic Pathway(s)
- A term used to describe chemical processes whereby metabolites
(proteins, fats and carbohydrates) are converted from one to
- The sum of all chemical processes that occur in our cells.
- Phenylalanine (PHE)
- One of the essential amino acids, (i.e. ones that must be provided
in the diet, as opposed to non-essential amino acids which can be
produced in the body). In most persons the level of PHE in the blood
is controlled by converting any excess to tyrosine (TYR), another
amino acid. In persons with PKU, PHE accumulates in the blood
because their cells are unable to convert PHE to TYR. The chemical
substance that converts PHE to TYR is called the phenylalanine
- A byproduct of PHE breakdown which is found at high levels in the
urine of persons with untreated PKU.
- Phenylketonuria (PKU)
- A hereditary condition, in which the liver cells cannot convert
PHE (phenylalanine) to TYR (tyrosine), recognized by an increased
blood phenylalanine level (hyperphenylalaninemia).
- An essential ingredient of all living matter. A chemical compound
made of building blocks called amino acids. Proteins have many uses
in the body: they are used as building materials, chemical messages,
regulators of chemical reactions (enzymes), and so on.
- Tyrosine (TYR)
- A non-essential amino acid which is made by the conversion of PHE
to TYR. It becomes an essential amino acid for the person with PKU,
since he or she cannot make their own from PHE.
What is PKU?
Phenylketonuria (PKU), also known as hyperphenylalaninemia, is a genetic
condition inherited from both parents, in which the body is unable to
use one of the constituents of a normal diet - an amino acid, called
phenylalanine (PHE). PHE is found in all protein foods such as meat,
eggs, fish, milk and cheese and to a lesser extent in cereals,
vegetables and fruits. Proteins are composed of amino acids, and when we
ingest proteins we break them down to amino acids which we then use to
build the kinds of proteins that we need. Furthermore, our bodies can
convert one amino acid to another, thus only some must be ingested, such
as PHE, while others (non essential amino acids) can be created by
conversion. In PKU, PHE can not be converted to TYR, and so PHE
accumulates in the blood, this excess can retard physical and
intellectual development. TYR deficiency per se does not occur because
the diet provides sufficient TYR.
The Heredity of PKU
As was mentioned above, PKU is a metabolic deficiency (genetic
condition) inherited from both parents. But what does that really mean?
Genetic conditions are caused by abnormal genes. The mother's egg
contains genes on 23 nuclear chromosomes. The father's sperm also
contains copies of those genes on his 23 chromosomes. At conception the
two sets combine to give us 23 pairs of chromosomes (for a total of 46).
It is estimated that each of us 'carries' at least 10 genes which have
been seriously altered as a result of mutation. In most people the net
result of these alterations is never experienced because we still have
that other chromosome with a backup copy of the gene from the other
parent. People who receive an altered gene from their parents are called
carriers. A female carrier will have some eggs with the defective gene
and some with the normal gene. A male carrier will have some sperm with
the defective gene and some with the normal gene. If two carriers have a
child together and each of them contributes an egg or sperm with a
defective gene, that child will have the condition. If the gene that is
altered is the gene responsible for the conversion of PHE to TYR, the
child is affected with PKU. Every time two carriers conceive a child,
the probability that that child will receive the two chromosomes with
altered genes is one in four, or 25%. The chance that a child will be an
unaffected carrier is two in four, or 50%, and finally the chance that
the child will be unaffected and not a carrier is one in four, or 25%.
This type of heredity is called Autosomal Recessive Inheritance. Figure
1 is a schematic representation of this type of inheritance, A's
represent a functioning gene, whereas a's represent the altered
NOTE: Despite all our efforts, we could not find if
the above picture had or not a copyright. If you happen to know if, in
fact, there is, we would appreciate knowing about it, and imediately
give the credits to the owners. Thanks.
Consequences, i.e. PKU
Without prompt treatment the accumulation of PHE in the blood results in
progressive brain damage; this is especially so during the early months
of life, when there is very rapid brain growth. World wide research has
demonstrated that if diagnosis is made and treatment is started in the
first few weeks of life, normal brain development is not disturbed. It
is essential to point out that good dietary control must be maintained
for years, perhaps for life, in order for the positive results to
persist. The issue of when to discontinue the PKU diet, is the focus of
some controversy. It used to be thought that it could be discontinued in
late childhood, after the completion of the rapid brain development.
However, research has shown benefits of continuation of this diet well
into adulthood, and even indefinitely. Adults with PKU who chose to
remain on the diet may benefit from increased ability to concentrate and
hence be able to achieve greater goals academically. At the Montreal
Children's Hospital, we now recommend that individuals with PKU remain
on the diet for life. Individual needs should be discussed with a
dietitian in order to determine adaptation of the diet in adulthood. The
following passage illustrates early treated PKU.
L. Levy, MD, FAAP, Phenylketonuria-1986, Pediatrics in review, vol.7,
no.9, March, 1986)
L. Levy, MD, FAAP, Phenylketonuria-1986, Pediatrics in review, vol.7,
no.9, March, 1986 .
This case illustrates the prevention of mental retardation in PKU by
identification shortly after birth and early dietary treatment, the
reduction in IQ and other deficits that are often seen when the diet is
discontinued during childhood, and the emergence of maternal PKU as an
issue for adolescent girls.
- This girl came to attention when her newborn screening blood
specimen collected at four days of age indicated a phenylalanine
concentration of 20 mg/dL (equivalent to 1200 µmol/L). She was
referred to a metabolic center for evaluation. There, PKU was
confirmed on the basis of a plasma phenylalanine level of 41 mg/dL
(2460 µmol/L)and normal concentrations of other amino acids. At
eight days of age, she began a phenylalanine-restricted diet. This
resulted in excellent metabolic control of blood phenylalanine
levels (2 to 10 mg/dL or 121 to 600 µmol/L) and normal growth and
development. When she was 5 years old, the diet was discontinued, in
accordance with the clinic's policy at that time. Her intelligence
has remained within normal range and she has completed high school
with a 'C' average. However, her measured IQ has decreased from 132
at 5 years of age to 85 at 16 years of age, and her psychology
assessments have disclosed deficits in visuomotor and fine motor
performance. She recently became engaged and she and her fiancee
have participated in discussions about maternal PKU. Emphasis has
been given to the need for careful pregnancy planning so that the
fetus can be protected by initiation of the phenylalanine-restricted
diet prior to conception and its continuation throughout pregnancy.
Women with PKU who have been properly treated throughout childhood and
adolescence can develop normally, lead normal lives, and have normal
IQs. However, if they are no longer following a strict low PHE diet
their blood will contain high levels of PHE, which is very dangerous for
a developing baby. We strongly recommend that women with PKU use
reliable methods of contraception to prevent unplanned pregnancies. When
they are ready to have a child, they should speak to a metabolic team at
least six months before trying to become pregnant, to discuss treatment
It is possible for women with PKU to have normal children. They must be
able to strictly follow their low PHE diet from before the time they get
pregnant, throughout pregnancy until their baby is born. Their blood PHE
levels should be monitored weekly to ensure they remain within a healthy
range for their baby.
Even when proper PHE levels are maintained PKU women still have a higher
risk of giving birth to children with smaller than average head size and
who don't grow as quickly as other children. If they are unable to
maintain control of their PHE levels and they allow these levels to rise
the risks of having a baby with congenital heart disease, small head
size, mental retardation, and slower than average growth before and
after birth also rise.
Should a PKU woman begin an unplanned pregnancy she should immediately
seek medical advice from health care workers familiar with PKU. If she
is able to bring her blood PHE levels down to a safe range within the
first eight weeks of pregnancy her chances of having a healthy baby are
still quite good.
In populations of European descent, and other places where the people
are of "European" descent, about 1 infant in 10,000 is born
with Classical PKU. Classical PKU, if not treated in the first few weeks
of life, usually causes profound and irreversible brain damage. Children
affected with PKU are usually diagnosed shortly after birth when a
couple of drops of blood drawn from a heel prick reveal a high level of
phenylalanine in the blood. This is called a positive screening test. An
initial positive test does not necessarily mean that the child will have
PKU. A second test must be conducted to confirm the result of the first.
After diagnosis, the infant is treated without delay. The treatment for
PKU is a special diet which is selectively low in PHE, but contains
adequate amounts of other nutrients. Adherence to the diet is crucial in
infancy and childhood, and we now have reason to believe that it would
be beneficial to remain on it through life. The diet is supplemented
with a special formula contains very litlle phenylalanine but which
contains all other essential amino acids as well as vitamins and
minerals required for the child's normal development. A PKU diet is
prescribed by a physician, designed by a dietician, administered by the
parents, and monitored and revised over time as the child's nutritional
needs change, due to growth, illness, puberty, changing tastes and
eating habits. Some foods included in the PKU diet are not normally
available at regular grocery stores and so a special food distribution
center has been set up.
(See National Food
National Food Distribution Center (NFDC)
What is the National Food Distribution Center (NFDC)?
NFDC is a non-profit food bank which was set-up in 1974 by the MCH
Biochemical Genetics Unit and a Canadian team of doctors and counsellors
in the field of biochemical genetics. The Center imports a variety of
special foods useful for the treatment of certain metabolic diseases.
These products come from all over the world and are distributed by NFDC
to hospitals and clinics across Canada.
This service is provided to all canadians with metabolic conditions. In
Quebec, products are provided free of charge to elligible families,
while some canadian provinces charge a nominal fee for certain products.
Non-canadians with metabolic conditions who need low protein foods can
contact the International Foodbank. A letter from a doctor must
be provided for orders to be approved. International
Foodbank's website provides a list of available foods and a price
list in US dollars for international orders.
Who needs these foods?
There are over 1000 children in Canada alone who suffer from hereditary
metabolic diseases such as Phenylketonuria (PKU), Maple Syrup Urine
Disease (MSUD) and Galactosemia (GALT). Many of these children are on
severely restricted diets; they depend on the specialty foods that are
only available at the Center. Getting the right food, on time, is
therefore not a convenience but a medical necessity.
Different provinces have different methods of making NFDC products
available. In Quebec, once a child is diagnosed with a genetic disorder
which requires a special diet, the family is referred to the closest
clinic. This clinic will serve as an agent between the family and the
National Food Distribution Centre. It is important for representatives
to understand that these food orders are crucial for those who suffer
from genetic disorders. It is equally important for parents to
understand that these products are highly specialized and not always in
stock due to unpredictable production and availability fluctuations.
When should orders be placed?
The demand for the products distributed by the National Food
Distribution Center is difficult to forecast. The Center places regular
orders with suppliers overseas and in the United States, but it is not
unusual for some shipments to be delayed. Families and representatives
of hospitals and clinics should try to anticipate what foods they need
and, whenever possible, allow at least 3 weeks for delivery of these
highly specialized products. In this way, NFDC staff can better meet the
needs of patients across Canada. Of course, not all orders take this
long, but a little leeway makes the process easier for everyone involved
and helps minimize last-minute emergencies.
How are orders placed?
To order products, representatives from hospitals and medical clinics
can fax or mail their food orders to the following address:
Biochemical Genetics Unit
Once the order is registered at the Montreal Children's Hospital, it is
faxed to the FDC for completion. There is a particular form to fill out
when writing an order and you must ensure that the name and diagnosis of
the patient is clearly inscribed, as well as the product name or code
number and the quantity required. The address where the food is to be
delivered should always be specified, along with the name of the
representative who placed the order. Other provinces have different
methods of specialty products distribution : ask your metabolic
specialist for details.
Montreal Children's Hospital,
2300 Tupper, Room A-718
Montreal, Quebec, H3H 1P3
fax: (514) 412-4329
NOTE: If your country or region does not have such a resource, perhaps
it could be established. The interest of parents was an important
stimulus for the Canadian initiative.
Individuals with PKU receive a diet containing limited phenylalanine.
Foods such as meat, fish, eggs, cheese, milk products, legumes, and
bread, which are high in PHE are eliminated or greatly reduced.
Artificial protein substitutes are given which contain amino acids
without phenylalanine. These formulas, such as Phenex-1 and Phenylfree,
are designed to meet the specific needs of children with PKU. The
dietician will calculate the exact amount of formula required for your
child. It is essential that this is taken daily, preferably 2 to 3 times
a day in order to insure proper growth and nutritional balance. Accurate
measurement and careful mixing of this formula is necessary. For infants
up to 4 months of age, use freshly boiled water (cooled) and sterilize
bottles and equipment. For older children, the formula is mixed with
water. If your child prefers, this may be flavored with additives such
as vanilla, sugar, or flavor extracts.
Your child cannot survive on formula alone. Some phenylalanine is
necessary in his or her diet. This is essential for growth and is taken
as a specific amount of breast milk or regular infant formula for
babies, or food exchanges in older children. Your child will be
instructed as to the precise intake of phenylalanine required, which
will vary with each individual. The requirement depends on which type of
PKU your child has (e.g. severe vs. mild) and the period of growth they
are in. We use the methods of exchanges, or choices, where one exchange
is equal to 15 mg of phenylalanine; for example ¼ cup of fresh or
cooked carrots is equivalent to one exchange. A list of food exchanges
can be obtained from your dietician. A new-born baby with classic PKU
may require 20 exchanges a day, a five year old requires between 14 and
30 exchanges, and an adult woman requires between 15 and 50 exchanges a
day. We encourage our families to become familiar with the methods of
calculating these exchanges. Free foods, those without phenylalanine,
such as tapioca pudding may be given as desired.
Your child may experience eating problems that are common and can be
managed with patience and determination. As your child gets older, he or
she will understand that maintaining good dietetic control is to his or
her advantage. We recommend that the exchanges (allowed phenylalanine)
be distributed evenly throughout the day in order to keep the diet as
normal and balanced as possible. Your dietitian will carefully balance
the calories, protein, carbohydrates, and fats required by your child so
that the diet is optimal for proper growth and development.
- Diet sweeteners such as Nutrasweet®, Sweetmate®,
Canderal®, or aspartame® are made from phenylalanine
and aspartic acid. Thus, patients with PKU should avoid diet food
and drinks containing high PHE sweeteners.
- Social eating: Occasionally your child may be invited to a
social gathering when the diet is cumbersome. We want your child to
go! We strongly encourage you NOT to let the diet interfere with
social activities, even the ones involving food. Your dietitian may
advise you as to how the diet can be adjusted before such events
which will allow some liberalisation of the diet on those specific
Which May Occur & How We Can Help
- Skin rashes and diarrhea:
If your child develops a skin rash and/or diarrhea, the phenylalanine
ingested may be too low and may need readjustment. Phone your
metabolic center to discuss this.
Routine immunisations are most commonly given at the usual times.
Discuss this with your child's pediatrician.
When your child develops a cold or infection, during these times their
blood phenylalanine may rise temporarily. Please encourage adequate
calories by supplementing the diet with items such as "free
foods" : sugary drinks, vegetables, and so on. In a day or two,
the level usually reverts to normal. If the infection persists or if
there is persistent vomiting or continued poor appetite, please
contact your metabolic center.
Research in progress
Apart from providing a clinical service, our centre is actively involved
in PKU research. This research / clinical interphase helps us and also
you, the families, in understanding the biochemical basis of the
particular type of PKU in your family and facilitates its management.
Since the gene causing PKU was identified by Savio Woo and colleagues in
the mid 80's, more than 350 disease-causing mutations (or changes in the
gene) have been identified. Some of these mutations appear to originate
in specific European populations and may give us information about your
family history. Knowing the mutation may also help predict the enzyme
activity and the type of PKU your child has, and may be used as an
initial guide to his/her particular phenylalanine requirements. In our
laboratory, we have established an efficient method to scan for these
We are also involved in research for the development of a different type
of treatment that puts less of a burden on the patient and their family
than does the traditional dietary therapy. The aim of this research is
to make an enzyme which, taken orally, can degrade phenylalanine in the
digestive tract before it is absorbed into the body. With this treatment
we hope that patients would be able to at least relax their diet if not
eliminate it entirely.
Our Division maintains a database for information regarding the many
types of PKU mutations. This database is maintained by Manyphong
Phommarinh, Mélanie Hurtubise, Lynne Prevost and Charles R. Scriver. It
is now on the Internet (via the World Wide Web), as you already know if
that is where you obtained this booklet, if not you may try the
following address: http://www.pahdb.mcgill.ca
If you reside in Quebec, please contact us for a list of available
foods, and the order form. Otherwise, please contact your local
metabolic diseases center.
The key to successful management of PKU is careful
monitoring of blood PHE levels. This is done by regular blood testing
either by drawing blood at the hospital, or by pricking a finger or heel
with a special sterile lancet, and dripping some drops of blood onto a
special paper, called a Guthrie Card, which is then sent for analysis to
the provincial center. Figure 2 is an example of the well controlled
blood phenylalanine level of one of our patients. For directions on how
to perform the blood tests at home please see Home Blood Testing below.
Fig.2. Successful Monitoring and control.
NOTE: Some values are omitted here for the purpose of clarity.
This graph represents the average monthly PHE levels monitored
monthly after birth in January, and over 2 weeks after 6 months of age.
The baby was born with an extremely high level of PHE, which was
controlled by diet. It can be seen that after June, the PHE levels
remain, more or less, within the upper and lower limits. With this type
of continual control, the parents and child can most likely expect
normal physical and mental development.
Home Blood Testing
The blood test procedure outlined below is generally carried out:
- Birth to 3 years old tested weekly or every two weeks,
- 3 to 7 years old tested every two weeks,
- 7 years and older tested monthly.
NOTE: It is the parents' responsibility to arrange blood tests at the
hospital. We do however encourage that parents learn to perform the
blood test procedure outlined below and mail the test paper into the
test center when PHE values are under good control. In addition, our
dietitian will carefully monitor your child's weight gain and growth
throughout their development, so that we can know what adjustments to
make in the diet, the frequency and procedure for blood tests, as well
as frequency of medical check-ups.
for home Guthrie Blood test procedure
Source: Réseau de Médecine Génétique du Québec, Instructions
pour un prélèvement de sang adéquât sur papier filtré, 11/95.
- Warm the heel or finger to be pricked.
- You may hold the heel or finger lower than chest level, and / or
gently squeeze the area.
- Sterilise the skin with alcohol and sterile gauze.
- Prick with sterile lancet.
- Allow a large drop to form on the skin surface.
- Allow drop to drip onto the centre of circle.
- Drip consecutive drops also in the centre so that it stays moist
and the blood spreads (soaks) out from the centre to the edges of
the circle. DO NOT allow the blood to dry before applying the next
- Fill 3 out of the five circles.
- Make sure that the circles are completely filled and not
- Allow the Guthrie strip to air dry.
A Sense of Optimism
Because of the fact that effective treatment is readily available some
people regard PKU as a disease of the past. You are however already
aware that living with a loved one with PKU is far from trivial.
Metabolic Units are designed to treat PKU and other metabolic diseases
seriously and help patients and their families cope with these diseases
at different levels. The metabolic team will help you medically, for
example, when your child is ill, they should be notified in case their
advice or intervention becomes necessary. They will help with the low
protein diet and diet-related problems. Dietitians are there to give
advice as your child grows, copes with minor illnesses, develops
different tastes, and so on. Genetic counsellors are also available to
answer your questions. When you need information about PKU, they can
provide it. When your child reaches the age of making reproductive
decisions, they are there to speak with him or her, to make sure that as
an adult, he or she understands the condition and its hereditary
aspects. Finally, many metabolic teams are active in PKU research.
Research may in the future lead to even better management of PHE levels,
and even better treatment strategies.
Contacts and Links
- The Canadian Society For Metabolic Disease
Sharon Jamieson, Treasurer/InfoCo-ordinator
Coquitlam, British Columbia, Canada V3C 3X6
Phone: (604) 464-1017
- National Food Distribution Center
Roman Bhattacharya, Manager
1030 Rue St. Alexandre, Suite 300
Montreal, Quebec, Canada H2Z 1P3
- PKU Canada Inc. Family Association
Hospital for Sick Children
555 University Avenue
Toronto, Ontario, Canada M5G 1X8
Phone: (416) 813-6356
Fax: (416) 813-5745
- National Society for PKU (NSPKU)
7 Lingey Lane
Wardley, Gateshead, Tyne & Wear NE10 8BR
- Research Trust for Metabolic Diseases in
Golden Gates Lodge
Crewe, Cheshire, UK CW1 1XN
Phone: 01270 250221
Fax: 01270 250244