By Virginia Schuett, Editor, National PKU News
Families of children with late-diagnosed children can take heart from a new study that strongly supports the value of long-term treatment for children who are diagnosed with PKU after infancy. This study contradicts what many physicians believed years ago, when most families were told that it was "too late" and treatment would not benefit their late-diagnosed children—even those found to have PKU as toddlers. The common and tragic belief was that the diet was only of value for newborns, before any brain damage had occurred.
Fortunately, some people, such as Dr. Richard Koch of Los Angeles Children’s Hospital, have always recommended diet treatment for late-diagnosed persons. Nearly all of his late-diagnosed individuals have attempted the diet. Thus, he has a significant population of such adults, who have been treated for many years. The experience with these adults shows us how mistaken is the old idea about PKU treatment.
Dr. Koch, with several colleagues in the Dept. of Pediatrics and the Research Institute at Children’s Hospital, collaborated with Dr. Per Guldberg and Dr. Flemming Güttler of Denmark on this research. They did follow-up assessments on 57 late-diagnosed persons managed by Children’s Hospital. PKU was diagnosed from 3 months to 43 years of age, with an average at age 8. Late diagnosis was due to a child being born before newborn screening or, for a great variety of reasons, being missed in screening.
Twenty-eight of this group have remained on a phe-restricted diet continuously since the time of their diagnosis. The average I.Q. (intelligence quotient) at the time of diagnosis was just 44 (moderately retarded), with a range of "non-measurable" (the person diagnosed at age 43) all the way up to 100 (average for a normal population). The current average I.Q. for this group was 73 (from "non measurable" to 108). That represents an average 30 point increase in I.Q.! For all adults who were treated more than 19 years at the time of the study, the average I.Q. was 82 (range 69-108), regardless of when the diet was started and regardless of the initial I.Q.
For the 12 adults with the best diet control throughout (75% of blood phe levels under 15 mg/dl), the average I.Q. was now 82. The 7 with poor control (75% of blood phe levels above 15 mg/dl) had a smaller average I.Q. increase, to just 61. The rest, with fair control (50% of blood phe levels less than 15 mg/dl) had an average I.Q. of 77. In marked contrast, six adults who were diagnosed at an average of 4.3 years and had an I.Q. of 43 at the time of diagnosis, but were never treated, now had an average I.Q score of only 18. These data clearly show the importance of diet and quality of treatment to ultimate outcome, regardless of age at diagnosis.
In the group of 28 continuously treated persons, 9 are employed, 6 are in college, 3 attend a workshop, and 10 have never worked. Nine are married; there are 7 children born to these couples (one is intellectually gifted). For the group that was never treated, all were institutionalized with the exception of one adult who for unknown reasons did not become mentally retarded even without treatment (interestingly, he had a brother who was severely retarded).
The study also looked at a group of 8 late-treated adults who were on the diet for some period of time, then stopped the diet, and later resumed it as adults (after 6 to 34 years off-diet). The reasons for returning to the diet were a mental illness diagnosis (including agoraphobia and panic attacks), recurrent headaches in one adult, and brain MRI changes in one. The off-diet problems experienced by this group are not different than those experienced by many early-treated adults who stop the diet. (Personal communication with Dr. Koch: The mental illness and headaches significantly improved or resolved after diet was restarted in these adults. Two women returned to diet for pregnancy and had normal babies.)
Sadly, there are still a few children with PKU being missed in newborn screening programs or are late-treated due to lack of screening, as in countries like Jordan. However, families should remain optimistic about the eventual intelligence of their children if they are treated continuously into adulthood and have good control. Among the group Dr. Koch studied, the 8 persons who had started treatment by age 1 1/2 years had an average I.Q. of 96 (range 85-108), nearly average for an adult population. Even treatment started at age 2 to 3 1/2 years resulted in an average I.Q. of 80 (range 67-96). Treatment between 4 and 7 years of age resulted in an I.Q. of 79.8 (range 70-94).
Koch, R., et. al., Long-Term Beneficial Effects of the Phenylalanine-Restricted Diet in Late-Diagnosed Individuals with Phenylketonuria, Molecular Genetics and Metabolism 67: 148-155, 1999.