A survey was sent to the directors of 111 clinics in the United States that treat patients with phenylketonuria (PKU), and we received 87 responses. These 87 clinics were treating a total of 4,669 patients. Approximately one-half of the patients were younger than 12 years of age, and 93 percent of these were on a phenylalanine (Phe)-restricted diet. Of those patients 12 years of age and older, 54 percent were on a Phe-restricted diet. The survey instrument included questions about diagnosis, initiation of treatment, assessment of biochemical control, and continuation of dietary restriction.
The clinic directors were asked what concentration of Phe caused them to make a presumptive diagnosis of PKU and begin dietary restriction of Phe. For 70 of the 87 clinics (80 percent), a Phe concentration of 10 mg/dL or less (600 µM) was considered the appropriate level to begin dietary restrictions. At 10 of the 87 (11 percent), treatment began at a concentration of between 10 and 15 mg/dL (600 to 900 µM). Five clinics (6 percent) considered a concentration of more than 15 mg/dL (900 µM) the appropriate level to initiate
The clinic directors were asked about their approach to long-term treatment of PKU. Some 99 percent of the clinics prescribed a restricted diet for life for males; 85 percent prescribed a restricted diet for life for females. These practices had been in place for more than 7 years at 54 of the 87 clinics (62 percent), and for more than 3 years at 10 of the 87 (11 percent).
The most commonly advocated levels were 2 to 6 mg/dL (120-360 µM) for patients up to 12 years of age, and 2 to 10 mg/dL (120-600 µM) for patients older than 12 years of age.
Monitoring consisted of measurement of Phe concentration in a blood sample, collected at most centers from patients after they had fasted overnight. Monitoring intervals varied according to the age of patients. At less than 1 year of age, the mean frequency was 3.6 times per month (the range was 1 to 8 times per month). Between the ages of 1 and 3 years, the mean frequency was 1.9 times per month (the range was 0.33 to 4 times per month). The frequency of monitoring decreased with increasing age. By 18 years of age, the mean frequency was 1.0 times per month (the range was 0 to 4 times per month).
The laboratory technique used for measuring serum or plasma Phe varied from the semiquantitative Guthrie method used in 19 of the 87 clinics (22 percent) to highly quantitative plasma amino acid column chromatography used by 19 (22 percent) and HPLC by 4 (5 percent). A majority of the clinics (41 of the 87, or 47 percent) used the McCaman-Robins fluorometric method.
The amount of time between obtaining blood from patients and reporting the results to the family varied from 1 to 10 days. Most clinics reported the results within 1 to 3 days (52 of the 87, or 60 percent). Five clinics (6 percent) needed 8 to 10 days.
Deficiencies in our knowledge still affect our ability to treat patients with PKU optimally. Some involve the pathophysiology of central nervous system injury in PKU, such as the relationship of brain Phe concentration to outcome, the existence of modifying genetic factors, and genotype-phenotype correlation between phenylalanine hydroxylase (PAH) mutations and the clinical phenotype. Other deficiencies involve factors related to compliance with a restricted diet, such as how to design a more palatable diet. We also need a better definition of who should resume the diet. Ideally, a diet treatment that addressed abnormal PAH protein or the gene mutation in PAH may have the best chance of producing a normal outcome.
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