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Summary of a presentation by Dr. Sufin Yap and Dr. Eileen Naughten, National Center for Inherited Metabolic Disorders, The Children’s Hospital, Temple Street, Dublin, Ireland
The Irish national newborn screening program for PKU was implemented by Dr. Seamus Cahalane in 1966. Today, newborn screening is done at 3 to 5 days after birth on all babies. This now includes screening for PKU, as well as for homocystinuria, galactosemia, maple syrup urine disease, and hypothyroidism.
The total population in Ireland is currently 4.5 million. Since the start of newborn screening for PKU, testing has been done on 2.13 million babies. There were 470 positives, giving an incidence of 1 in 4,500. This is much greater than in the U.S., where the incidence is about 1 in 12,000. There are currently 611 individuals with PKU (334 males and 277 females) attending the National Centre for Inherited Metabolic disorders at The Children’s Hospital, Temple Street, Dublin.
Following Dr. Horst Bickel’s 1954 publication on the first dietary treatment of PKU, several physicians in Ireland began to treat PKU. When two of her early-treated patients in Dublin showed intellectual deterioration following cessation of the diet, Dr. Doreen Murphy decided that the Dublin clinic should be a “ Diet for Life” clinic. It has kept that policy since 1965.
The Diet
The aims of dietary treatment in Ireland are:
(1) to reduce phe levels to 200-400 µmol/L (3.3-6.6 mg/dl), (2) to provide adequate protein, energy, vitamins and minerals, replace tyrosine, and prevent deficiencies, and (3) to provide variety, palatability and flexibility to suit individual lifestyles. The diet has three components comprising of (1) a phe-free synthetic amino acid mix, (2) natural protein (where 1 exchange = 50 mg phe, and (3) phe-free foods.
Biochemical Control
We measure blood phe using a quantitative amino acid analyzer. Blood tests are done twice weekly initially, until levels stabilize. It is done weekly for ages 0-2 years, twice monthly for children between 2-5 years, and monthly thereafter. Results are given by phone with frequent clinic visits.
In the 1980’s, a retrospective study of the children who attend our clinic noted that the best outcome, as measured by intelligence quotient (I.Q.), was achieved in the group whose blood levels were 200– 400 µmol/L. Since then the clinic has aimed for this range.
Education of Parents and Child
Education of both parents and child is a continuing process throughout attendance at the clinic. This includes reassurance, giving out PKU handbooks, teaching the heel prick procedure for blood collection, teaching the importance of the three components of dietary treatment, and eventually getting a child to take responsibility for diet management. We organize cookery demonstrations and activity days. We also have a continuing education program at the clinic visits, tailored for each individual and each age group.
Adolescent Growth Period
Besides maintaining phe levels at the therapeutic range, the provision of adequate nutrition as well as preventing deficiencies are important aspects of diet treatment. This is particularly true during the adolescent growth spurt period where there is an increased requirement for certain vitamins and minerals. A study on 26 adolescents attending the clinic showed that 66% of males and 64% of females attained heights greater than the 25th percentile and 77% of males and 88% of females with weights of greater than the 25th percentile. Of these, 61% had overall good biochemical control for the past twelve months. These results show that it is possible to attain normal growth with good biochemical control.
Maternal PKU
Women with poor phe control at conception have an increased risk of spontaneous abortion, small-for-dates babies, and babies with microcephaly and structural heart defects. It is the policy of our clinic to encourage planned pregnancies with pre-conception phe levels of 150-250 µmol/L (2.5-4.2 mg/dl). This is slightly tighter control, to protect the fetus. Bloods are sent in twice weekly for phe monitoring, and we then make appropriate dietary adjustments to the natural protein intake. We prescribe adequate synthetic protein with additional tyrosine, adequate energy, vitamins, and minerals. To-date, we have had a total of 90 pregnancies with 77 surviving offspring. Fifty-six pregnancies were carried with the mother on diet while 34 were not on diet. There were a total of 12 miscarriages, one stillbirth and three infant deaths, all of whom were offspring of non-diet mothers. Forty-eight babies had head circumference > 3rd percentile; 43 were from mothers on diet (ER Naughten 2001).
Psychosocial Adjustments to Diet
It has often been argued that the risks to cognitive functioning in coming off the strict diet are far less important than the potential psychosocial strain of long term dietary treatment. Given Ireland’s longstanding diet-for-life policy, it was important to study the adjustment and treatment needs of adolescents who are continuing on a strict diet. Such a study on 51 adolescents was carried out in 1992, showing 41% achieved levels under 600 µmol/L (10 mg/dl). Only 8% had levels between 200-400 µmol/L. Self-esteem of the PKU group was slightly higher than that of non-PKU controls in the study. Teenagers with PKU were more positive about school. The strict dietary control and discipline needed for lifelong adherence to this treatment requires support and encouragement with frequent clinic visits. We have found that although diet compliance can be difficult, with attention to confidence, self-esteem and continued education, young adults with PKU can achieve an excellent outcome.
Previously Untreated Adults
Our policy for previously untreated adults is a trial of diet for a minimum 2-year period, with an assessment at the end of the trial period to determine whether to continue diet. After obtaining biochemical, medical, and diet profiles on the adults, we introduce the diet gently, with minimal disruption to the individual’s daily diet routines. We aim to reduce phe levels slowly, and provide a nutritionally adequate diet, made as appetizing as possible. There are now 21 on-diet adults in institutions, with 19 showing marked improvements. Another 17 are in the community and all 17 showed marked improvement since starting diet (M Kellett and ER Naughten 2001).
In summary, a positive, supportive clinic and positive, supportive parents can lead to independent young adults with PKU who accept the dietary discipline necessary for an excellent outcome.