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Phenylketonuria (Holistic)

Phenylketonuria (Holistic)

About This Condition

Early diagnosis is key to treating PKU, a rare genetic disorder that results in an amino acid imbalance in the body. According to research or other evidence, the following self-care steps may be helpful.
  • Fight back with fish oil

    Take a daily supplement containing 500 mg for every 8.8 pounds of body weight to prevent deficiencies caused by the PKU diet

  • Seek support from supplements

    Prevent vitamin and mineral deficiencies caused by the PKU diet by taking supplements that provide the daily value of L-tyrosine, vitamin K, vitamin B12, and selenium

  • Discover branched-chain amino acids

    Under a healthcare provider’s supervision, improve mental functioning by adding amino acid supplements to each meal and at bedtime; take 150 mg per 2.2 pounds (1 kg) of body weight each of valine and isoleucine, and 200 mg per 2.2 pounds (1 kg) of body weight of leucine

  • Monitor amino acids in your diet

    Work with your healthcare provider and a nutritionist to maintain a phenylalanine-restricted diet that is nutritionally adequate

  • Pass up aspartame

    Help prevent increased phenylalanine intake by steering clear of soft drinks, candy, and other foods and drinks sweetened with aspartame (Nutrasweet)

About

About This Condition

Phenylketonuria (PKU) is a rare genetic disorder that results in excessive accumulation of the amino acid , phenylalanine , and reduced levels of the amino acid, L-tyrosine , in the blood.1

If untreated, high levels of phenylalanine can cause severe mental retardation, behavioral disturbances, and other brain and nerve problems. Fortunately, newborn screening programs now identify most cases of PKU in the United States and other countries. Early diagnosis and treatment is the key to reducing or preventing PKU-related conditions.2 Gene therapy is currently being researched as a possible cure.3 , 4 Research is also being conducted on methods to decrease levels of phenylalanine in the blood through the use of certain enzymes5 and amino acids.6

Symptoms

Infants with PKU may be lethargic, feed poorly, and have a “mousy” odor from their sweat and urine. Eczema , sensitivity to sunlight , and light skin are also characteristic of PKU. Symptoms of children with untreated PKU include significantly diminished mental capacity, hyperactivity, and seizures.

Healthy Lifestyle Tips

Access to PKU resource/support groups, and education of family members may help simplify the complex dietary restrictions and improve one’s ability to follow them.7 , 8 , 9

PKU during pregnancy (maternal PKU) is of particular concern. Excessively high or low levels of phenylalanine may occur during pregnancy, both of which may adversely affect the fetus.10 Maternal PKU can lead to fetal malformations, including small head size (microcephaly), heart abnormalities, failure to grow properly in the uterus (called intrauterine growth retardation), and mental retardation.11 Adverse effects on the offspring can be reduced and by careful dietary control both prior to and during pregnancy.12 , 13 , 14Consultation and follow-up visits with medical and nutritional specialists are necessary for effective monitoring and dietary guidance in people with PKU.

Eating Right

The right diet is the key to managing many diseases and to improving general quality of life. For this condition, scientific research has found benefit in the following healthy eating tips.

Recommendation Why
Pass up aspartame
Avoid phenylalanine by steering clear of soft drinks, candy, and other foods and drinks sweetened with aspartame (NutraSweet).

There is debate about whether it is safe for people with PKU to consume aspartame, a low-calorie sweetener that contains about 50% phenylalanine. In one study, blood levels of phenylalanine increased only slightly after people with PKU ingested a 12-ounce soft drink sweetened with aspartame.15 However, that study did not address long-term effects of regular aspartame consumption. Until more is known, it is prudent for people with PKU to completely avoid aspartame-containing beverages and foods.

Monitor amino acids in your diet
Work with your healthcare provider and a nutritionist to maintain a nutritious phenylalanine-restricted diet, which usually means eliminating high-protein foods, such as dairy products, eggs, fish, meats, poultry, legumes, and nuts.

PKU can be controlled by a diet low in phenylalanine .16 The greatest benefits are achieved when the diet is started in the first few days of life,17 although later treatment will still help to reduce the severity of PKU-related conditions.18 , 19 , 20 Maintaining low phenylalanine levels through dietary control improves muscle control and behavioral and intellectual function.21 , 22

The effects of elevated phenylalanine appear to be less severe in older children and adults than in newborns and young children, in whom the nervous system is still developing. This, combined with the difficulties inherent in following a strict lifelong diet, have caused researchers to examine whether the dietary regimen may be relaxed as children get older. While some research suggests that relaxation of dietary measures may not be harmful,23 , 24 , 25 this has not been found to be true in all studies.26 Therefore, more research is needed to resolve this issue.27 , 28 In a survey of 111 PKU treatment centers, 87% favored lifelong dietary restriction of phenylalanine.29The PKU diet is strict, and should be undertaken with the help of a nutritionist and a physician.

A PKU diet is low in protein, providing no more than the minimum amount of phenylalanine needed by the body. All high-protein foods, such as dairy products, eggs, fish, meats, poultry, legumes, and nuts, are usually eliminated.30 Lower protein foods, such as fruits, vegetables and some grain products, are allowed in measured amounts, along with specially prepared phenylalanine-free or nearly phenylalanine-free foods. This diet is supplemented with an amino acid formula to increase protein intake without adding more phenylalanine than is nutritionally required.

Phenylalanine levels fluctuate as a consequence of changes in diet, health, and growth; therefore, levels must be checked regularly.31 A nutrition specialist can also provide information on homemade and specially prepared foods for people with PKU, including infant formulas, low protein pastas, breads, crackers, and other foods.

People with PKU who are not following the PKU diet can become deficient in biotin , a water-soluble B vitamin. This is because phenylalanine blocks biotin metabolism. In a controlled study of children with PKU, elevated phenylalanine levels resulted in seborrheic dermatitis caused by biotin deficiency, which was corrected by a return to the phenylalanine-restricted diet.32

Supplements

What Are Star Ratings?

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

Supplement Why
2 Stars
Branched-Chain Amino Acids
Take under medical supervision: 150 mg daily per 2.2 lbs (1 kg) of body weight each of valine and isoleucine, and 200 mg daily per 2.2 lbs (1 kg) of body weight of leucine
Regular use of branched-chain amino acids (BCAAs) may improve mental functioning.
In a double-blind trial, regular use of branched-chain amino acids (BCAAs) (i.e., valine, isoleucine, and leucine) by adolescents and young adults with PKU improved performance on some tests of mental functioning.33Participants received either placebo, or 150 mg per 2.2 pounds of body weight each of valine and isoleucine, and 200 mg per 2.2 pounds of body of leucine, taken with meals and at bedtime. Participants received one mixture or the other for four three-month periods, for a total of six months’ supplementation of each regimen over the course of a year.
2 Stars
Fish Oil
125 mg of oil or 15 mg of docosahexaenoic acid per 2.2 lbs (1 kg) of body weight daily
The PKU diet is low in fatty acids, some of which are essential for proper brain development. Supplementing with fish oil may improve the deficiency.
The PKU diet is low in fatty acids, some of which are essential for proper brain development.34 In one controlled study of children with PKU who were deficient in fatty acids, supplementation with fish oil (but not with black currant seed oil) for six months improved the deficiency. The children received 500 mg of oil per 8.8 pounds of body weight each day for 6 months. The amount varied from 5–8 capsules (each containing 500 mg) per day for each child.35 In another study, fish oil supplementation (providing 15 mg of docosahexaenoic acid per 2.2 pounds of body weight per day) improved body coordination and fine motor skills in children with PKU.36
2 Stars
L-Tyrosine
Consult a qualified healthcare practitioner
Supplementing with L-Tyrosine may help prevent a deficiency caused by the PKU diet and improve behavoir.
PKU results from a deficiency or malfunction of the enzyme, phenylalanine hydroxylase, which converts phenylalanine to . People with PKU have elevated concentrations of phenylalanine and low levels of L-tyrosine, which may contribute to behavior problems. In addition, low L-tyrosine levels in women with PKU may contribute to fetal damage. In some, but not all, double-blind studies, keeping L-tyrosine levels in the normal range by adding supplemental L-tyrosine to the diet improved behavior. In a preliminary study, blood L-tyrosine levels fluctuated significantly in people with PKU, suggesting a need for careful laboratory monitoring of people supplementing with L-tyrosine.
2 Stars
Selenium
Adolescents and adults: 55 mcg daily; for infants and children: 15 to 40 mcg daily, according to age
Selenium deficiency may develop on the PKU diet, and supplementation may help correct this.

People with PKU may be deficient in several nutrients, due to the restricted diet which is low in protein and animal fat. Deficiencies of long-chain polyunsaturated fatty acids (LC-PUFAs),37 , 38 , 39 selenium ,40 , 41 , 42 , 43 vitamin B12 ,44 and vitamin K may develop on this diet.45

Selenium is important for normal antioxidant function. Research suggests that selenium deficiency and decreased antioxidant activity may contribute to the brain and nerve disorders associated with PKU.46 In two preliminary studies involving selenium-deficient people with PKU, supplementation with selenium in the form of sodium selenite corrected the deficiency,47 whereas supplementation with selenium in the form of selenomethionine did not.48

1 Star
Vitamin B12 (Vitamin B12 Deficiency)
Refer to label instructions
Vitamin B12 is found almost exclusively in foods of animal origin, which are restricted on the PKU diet. Supplementing with vitamin B12 may correct a deficiency.

People with PKU may be deficient in several nutrients, due to the restricted diet which is low in protein and animal fat. Deficiencies of long-chain polyunsaturated fatty acids (LC-PUFAs),49 , 50 , 51 selenium ,52 , 53 , 54 , 55 vitamin B12 ,56 and vitamin K may develop on this diet.57

Vitamin B12 is found almost exclusively in foods of animal origin, which are restricted on the PKU diet. People on the PKU diet who are inconsistent in their use of a vitamin B12 supplement may become deficient in this vitamin. In a survey of young adults with PKU, 32% were found to have low or low-normal blood levels of vitamin B12.58 Vitamin B12 deficiency can cause anemia and nerve problems.

1 Star
Vitamin K
Refer to label instructions
People with PKU may be deficient in vitamin K, due to the restricted PKU diet. Supplementing with vitamin K may correct a deficiency.

People with PKU may be deficient in several nutrients, due to the restricted diet which is low in protein and animal fat. Deficiencies of long-chain polyunsaturated fatty acids (LC-PUFAs),59 , 60 , 61 selenium ,62 , 63 , 64 , 65 vitamin B12 ,66 and vitamin K may develop on this diet.67

Because the PKU diet is low in animal products, fat intake is also significantly reduced. The results of a preliminary study of children with PKU suggested that the low-fat PKU diet intake may impair the absorption of vitamin K , a fat-soluble vitamin, from the diet, possibly resulting in a vitamin K deficiency. In that study, children with PKU on a strict diet had low levels of certain vitamin K-dependent proteins needed for normal blood clotting.68

References

1. Diamond A. Evidence for the importance of dopamine for prefrontal cortex functions early in life. Philos Trans R Soc Lond B Biol Sci 1996;351:1483–93 [review].

2. Cabalska MB, Nowaczewska I, Sendecka E, Zorska K. Longitudinal study on early diagnosis and treatment of phenylketonuria in Poland. Eur J Pediatr 1996;155 Suppl 1:S53–5.

3. Eisensmith RC, Woo SL. Gene therapy for phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S16–9 [review].

4. Lin CM, Tan Y, Lee YM, et al. Expression of human phenylalanine hydroxylase activity in T lymphocytes of classical phenylketonuria children by retroviral-mediated gene transfer. J Inherit Metab Dis 1997;20:742–54.

5. Sarkissian CN, Shao Z, Blain F, et al. A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase. Proc Natl Acad Sci 1999;96:2339–44.

6. Pietz J, Kreis R, Rupp A, et al. Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. J Clin Invest 1999;103:1169–78.

7. Waisbren SE, Rokni H, Bailey I, et al. Social factors and the meaning of food in adherence to medical diets: results of a maternal phenylketonuria summer camp. J Inherit Metab Dis 1997;20:21–7.

8. Scheibenreiter S, Tiefenthaler M, Hinteregger V, et al. Austrian report on longitudinal outcome in phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S45–9.

9. Weglage J, Funders B, Ullrich K, et al. Psychosocial aspects in phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S101–4.

10. Brenton DP, Lilburn M. Maternal phenylketonuria. A study from the United Kingdom. Eur J Pediatr 1996;155 Suppl 1:S177–80.

11. Levy HL, Ghavami M. Maternal phenylketonuria: a metabolic teratogen. Teratology 1996;53:176–84 [review].

12. Cechak P, Hejcmanova L, Rupp A. Long-term follow-up of patients treated for phenylketonuria (PKU). Results from the Prague PKU Center. Eur J Pediatr 1996;155 Suppl 1:S59–63.

13. Cipcic-Schmidt S, Trefz FK, Funders B, et al. German Maternal Phenylketonuria Study. Eur J Pediatr 1996;155 Suppl 1:S173–6.

14. Rouse B, Azen C, Koch R, et al. Maternal Phenylketonuria Collaborative Study (MPKUCS) offspring: facial anomalies, malformations, and early neurological sequelae. Am J Med Genet 1997;69:89–95.

15. Mackey SA, Berlin CM Jr. Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients. Clin Pediatr 1992;31:394–9.

16. Diamond A. Evidence for the importance of dopamine for prefrontal cortex functions early in life. Philos Trans R Soc Lond B Biol Sci 1996;351:1483–93 [review].

17. Cockburn F, Clark BJ. Recommendations for protein and amino acid intake in phenylketonuric patients. Eur J Pediatr 1996;155 Suppl 1:S125–9.

18. Koch R, Moseley K, Ning J, et al. Long-term beneficial effects of the phenylalanine-restricted diet in late-diagnosed individuals with phenylketonuria. Mol Genet Metab 1999;67:148–55.

19. Yannicelli S, Ryan A. Improvements in behavior and physical manifestations in previously untreated adults with phenylketonuria using a phenylalanine-restricted diet: a national survey. J Inherit Metab Dis 1995;18:131–4.

20. Williams K. Benefits of normalizing plasma phenylalanine: impact on behavior and health. A case report. J Inherit Metab Dis 1998;21:785–90.

21. Arnold G, Kramer BM, Kirby RS, et al. Factors affecting cognitive, motor, behavioral and executive functioning in children with phenylketonuria. Acta Paediatr 1998;87:565–70.

22. Baumeister AA, Baumeister AA. Dietary treatment of destructive behavior associated with hyperphenylalaninemia. Clin Neuropharmacol 1998;21:18–27 [review].

23. Griffiths P, Ward N, Harvie A, Cockburn F. Neuropsychological outcome of experimental manipulation of phenylalanine intake in treated phenylketonuria. J Inherit Metab Dis 1998;21:29–38.

24. Griffiths P, Smith C, Harvie A. Transitory hyperphenylalaninaemia in children with continuously treated phenylketonuria. Am J Ment Retard 1997;102:27–36.

25. Cerone R, Schiaffino MC, Di Stefano S, Veneselli E. Phenylketonuria: diet for life or not? Acta Paediatrica 1999;88:664–6.

26. Diamond A, Prevor MB, Callender G, Druin DP. Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monogr Soc Res Child Dev 1997;62:1–208.

27. Griffiths P, Ward N, Harvie A, Cockburn F. Neuropsychological outcome of experimental manipulation of phenylalanine intake in treated phenylketonuria. J Inherit Metab Dis 1998;21:29–38.

28. Ullrich K. Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997. Eur J Pediatr 1999;158:46–54.

29. Fisch RO, Matalon R, Weisberg S, Michals K. Phenylketonuria: current dietary treatment practices in the United States and Canada. J Am Coll Nutr 1997;16:147–51.

30. Start K. Treating phenylketonuria by a phenylalanine-free diet. Prof Care Mother Child 1998;8:109–10 [review].

31. Davidson PW. Factors affecting cognitive, motor, behavioral and executive functioning in children with phenylketonuria. Acta Paediatr 1998;87:565–70.

32. Schulpis KH, Nyalala JO, Papakonstantinou ED, et al. Biotin recycling impairment in phenylketonuric children with seborrheic dermatitis. Int J Dermatol 1998;37:918–21.

33. Berry HK, Brunner RL, Hunt MM, et al. Valine, isoleucine, and leucine. A new treatment for phenylketonuria. Am J Dis Child 1990;144:539–43.

34. Giovannini M, Agostoni C, Biasucci G, et al. Fatty acid metabolism in phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S132–5.

35. Agostoni C, Riva E, Biasucci G, et al. The effects of n-3 and n-6 polyunsaturated fatty acids on plasma lipids and fatty acids of treated phenylketonuric children. Prostaglandins Leukot Essent Fatty Acids 1995;53:401–4.

36. Beblo S, Reinhardt H, Demmelmair H, et al. Effect of fish oil supplementation on fatty acid status, coordination, and fine motor skills in children with phenylketonuria. J Pediatr 2007;150:479–84.

37. Agostoni C, Marangoni F, Riva E, et al. Plasma arachidonic acid and serum thromboxane B2 concentrations in phenylketonuric children negatively correlate with dietary compliance. Prostaglandins Leukot Essent Fatty Acids 1997;56:219–22.

38. Giovannini M, Agostoni C, Biasucci G, et al. Fatty acid metabolism in phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S132–5.

39. Poge AP, Baumann K, Muller E, et al. Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake. J Inherit Metab Dis 1998;21:373–81.

40. Jochum F, Terwolbeck K, Meinhold H, et al. Effects of a low selenium state in patients with phenylketonuria. Acta Paediatr 1997;86:775–7.

41. Kauf E, Seidel J, Winnefeld K, et al. Selenium in phenylketonuria patients. Effects of sodium selenite administration. Med Klin 1997;92 Suppl 3:31–4 [in German].

42. Sierra C, Vilaseca MA, Moyano D, et al. Antioxidant status in hyperphenylalaninemia. Clin Chim Acta 1998;276:1–9.

43. Gropper SS, Naglak MC, Nardella M, et al. Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets. J Am Coll Nutr 1993;12:108–14.

44. Hanley WB, Feigenbaum AS, Clarke JT, et al. Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S145–7.

45. Schulpis KH, Platokouki H, Papakonstantinou ED, et al. Haemostatic variables in phenylketonuric children under dietary treatment. J Inherit Metab Dis 1996;19:603–9.

46. Sierra C, Vilaseca MA, Moyano D, et al. Antioxidant status in hyperphenylalaninemia. Clin Chim Acta 1998;276:1–9.

47. Kauf E, Seidel J, Winnefeld K, et al. Selenium in phenylketonuria patients. Effects of sodium selenite administration. Med Klin 1997;92 Suppl 3:31–4 [in German].

48. Lombeck I, Jochum F, Terwolbeck K. Selenium status in infants and children with phenylketonuria and in maternal phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S140–4.

49. Agostoni C, Marangoni F, Riva E, et al. Plasma arachidonic acid and serum thromboxane B2 concentrations in phenylketonuric children negatively correlate with dietary compliance. Prostaglandins Leukot Essent Fatty Acids 1997;56:219–22.

50. Giovannini M, Agostoni C, Biasucci G, et al. Fatty acid metabolism in phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S132–5.

51. Poge AP, Baumann K, Muller E, et al. Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake. J Inherit Metab Dis 1998;21:373–81.

52. Jochum F, Terwolbeck K, Meinhold H, et al. Effects of a low selenium state in patients with phenylketonuria. Acta Paediatr 1997;86:775–7.

53. Kauf E, Seidel J, Winnefeld K, et al. Selenium in phenylketonuria patients. Effects of sodium selenite administration. Med Klin 1997;92 Suppl 3:31–4 [in German].

54. Sierra C, Vilaseca MA, Moyano D, et al. Antioxidant status in hyperphenylalaninemia. Clin Chim Acta 1998;276:1–9.

55. Gropper SS, Naglak MC, Nardella M, et al. Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets. J Am Coll Nutr 1993;12:108–14.

56. Hanley WB, Feigenbaum AS, Clarke JT, et al. Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S145–7.

57. Schulpis KH, Platokouki H, Papakonstantinou ED, et al. Haemostatic variables in phenylketonuric children under dietary treatment. J Inherit Metab Dis 1996;19:603–9.

58. Hanley WB, Feigenbaum AS, Clarke JT, et al. Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S145–7.

59. Agostoni C, Marangoni F, Riva E, et al. Plasma arachidonic acid and serum thromboxane B2 concentrations in phenylketonuric children negatively correlate with dietary compliance. Prostaglandins Leukot Essent Fatty Acids 1997;56:219–22.

60. Giovannini M, Agostoni C, Biasucci G, et al. Fatty acid metabolism in phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S132–5.

61. Poge AP, Baumann K, Muller E, et al. Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake. J Inherit Metab Dis 1998;21:373–81.

62. Jochum F, Terwolbeck K, Meinhold H, et al. Effects of a low selenium state in patients with phenylketonuria. Acta Paediatr 1997;86:775–7.

63. Kauf E, Seidel J, Winnefeld K, et al. Selenium in phenylketonuria patients. Effects of sodium selenite administration. Med Klin 1997;92 Suppl 3:31–4 [in German].

64. Sierra C, Vilaseca MA, Moyano D, et al. Antioxidant status in hyperphenylalaninemia. Clin Chim Acta 1998;276:1–9.

65. Gropper SS, Naglak MC, Nardella M, et al. Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets. J Am Coll Nutr 1993;12:108–14.

66. Hanley WB, Feigenbaum AS, Clarke JT, et al. Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S145–7.

67. Schulpis KH, Platokouki H, Papakonstantinou ED, et al. Haemostatic variables in phenylketonuric children under dietary treatment. J Inherit Metab Dis 1996;19:603–9.

68. Schulpis KH, Platokouki H, Papakonstantinou ED, et al. Haemostatic variables in phenylketonuric children under dietary treatment. J Inherit Metab Dis 1996;19:603–9.

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