SpecialDietsfor Infants With Inborn Errorsof Amino ...SpecialDietsfor Infants With Inborn Errorsof Amino AcidMetabolism Infants with certain inborn errors of amino acid metabolism

AMERICANACADEMY OF PEDIATRICS

Committee on Nutrition

SpecialDiets for Infants With Inborn Errorsof AminoAcid Metabolism

Infants with certain inborn errors of amino acidmetabolism can be treated with special diets thatrestrict one or more amino acids to the minimumessential for normal growth. The principles ofsuch dietary therapy have been described in anearlier Academy 1

Phenylketonuria is the best known inborn errorof amino acid metabolism whose response todietary management has been evaluated extensively. Considerable experience with dietarymanagement has also been obtained from patientswith maple syrup urine disease, hereditary tyrosinemia, histidinemia, and some types of homocystinuria. Although dietary management can yielddramatic clinical improvement in these patients,a gap between the theory of treatment and itspractice still remains. The Committee believesthis gap can be narrowed by better use of foodtechnology and better application of nutritionalinformation.

The Food and Drug Administration (FDA) haschanged its policy about the special products usedfor dietary management of children with inborn

°Anessential amino acid is one that cannot be synthesized inmammals; the organism is dependent on an environmental

source to sustain protein balance. The essential amino acidsfor humans are: threonine, methionine, valine, isoleucine,leucine, phenylalanine, lysine, and tryptophan. In addition,infants require histidine.tA limiting amino acid is one that can be synthesized in theorganism but at a rate too slow to meet all the requirementsfor normal metabolism and growth in children. A supplementary dietary source is then required. Cystine, tyrosine,and arginine may be considered to be limiting amino acidsunder certain circumstances for infants.

errors of metabolism. The FDA has informed

manufacturers and users of the special diet prepa

rations or the constituent amino acids that suchproducts are now “¿�foodsfor special dietaryuses.―2 Previously, these special products wereclassified as drugs; and investigational new drugapplications were required by the FDA for theiruse. This change in policy has had two salutaryeffects. First, existing products are now morereadily available to treat patients with a variety ofhereditary aminoacidopathies. Second, food technologists can be encouraged to develop newproducts for treatment of a variety of medicalconditions.

The purpose of this statement is to bring thischange in FDA policy to the attention of pediatricians, and to provide them with informationabout existing dietary products for children withamino acid disorders. This statement also will tellpediatricians where they can obtain emergencyconsultation and dietary supplies. Recommendations are made to improve delivery of the needednutritional services.

THE TREATMENTREGIMEN:PRINCIPLES

Management of an hereditary aminoacidopathy may require the restriction of dietary intakeof one or more amino acids at the level ofminimum requirement. Only disorders concernedwith essential amino acids° and limitingt aminoacids will be considered here.

Supported by grant DHEW-FDA CA-272 from the Food andDrug Administration.

PEDIATRICS Vol. 57 No. 5 May 1976 783

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The amount of the restricted amino acidprovided by the diet must be sufficient to meetthe metabolic requirements dependent on it,including the requirement for growth; yet, itsintake must not permit an excess accumulation inbody fluids of the amino acid or its derivatives.The requirements for nutrient can be met byproviding a semisynthetic diet, derived eitherfrom a modified protein hydrolysate or from amixture of L-amino acids, so the diet containseither an extremely low amount of the implicatedamino acid or is free of it. Other dietary sources ofprotein can furnish the implicated amino acid(s)in an amount sufficient to sustain normal metabolism, yet low enough to avoid toxicity. Requirements for other nutrients—calories, fat (includingessential fatty acids), carbohydrates, minerals, andvitamins—are met either by special dietaryformulations added to the amino acid product orby further supplementation with natural foods ofknown composition.

Infants in the first six months of life traditionally receive all or most of their nutrient requirements from breast milk or infant formula. Duringthis period it is relatively easy to meet all thenutritional needs of an infant with an inborn errorof amino acid metabolism by providing a semisynthetic dietary product prepared from suitablytreated protein hydrolysates or amino acidmixtures and fortified with the required additional nutrients to meet the standards of an infantformula.35 Small amounts of milk are added tomeet the requirements of the restricted aminoacid(s).

Other foods are introduced into the diet as theinfant grows. The composition of these foods andthe quantities ingested must be regulated to keepthe amino acid composition of the diet undercontrol and to assure provision of other nutritional requirements. Additional modified proteinhydrolysates or specific amino acid mixtures lowin, or devoid of, the restricted amino acid(s) andfortified with modular components of diet whichsupply vitamin and/or mineral mixtures and

various sources of calories are also necessarycomponents of the diet. These products, whenappropriately formulated, make it easy to meetthe requirements for other amino acids andpermit a wider variety of natural foods to be usedin balancing the diet.

Careful monitoring of treatment and its effectis essential throughout the period of dietarymanagement. Total nutritional intake, includingthe micronutrient composition, should be knownand monitored to be certain the child is receivinga nutritionally adequate diet.6 The concentration

of appropriate amino acids in blood should bedetermined often enough to assure that the levelis adequate to sustain normal protein metabolism,but not high enough to be harmful. The childmust be observed frequently to be certain thatnutritional deficiencies do not develop.

Dietary constraints of the type required for

treatment of the inborn errors of amino acidmetabolism can engender difficulties for patientand family. Frequent and open communicationbetween parents and physician in this difficultarea can be aided by the recruitment of alliedhealth personnel, e.g., nutritionists, social workers, genetic counselors, and@ Thecompetence and availability of these healthworkers are essential to help parents implementthe dietary prescriptions.

The principles of therapy call for developmentof a precise diet appropriate to the problem,nutritional surveillance to assure that the diet isadequate, mechanisms for follow-up of the childfor symptoms or signs of nutritional deficiency ortoxicity, and provision of general support for thechild.

PRODUCTSAVAILABLEFOR DIETARYMANAGEMENTOF PHENYLKETONURIALow PhenylalanineProducts

Lofenalac, the first commercial product madewidely available for the dietary management ofphenylketonuria, contains a low (0.08 gm / 100gm) but significant amount of phenylalanine.Lofenalac is made from an enzymatic hydrolysateof casein. It also contains carbohydrate (cornsyrup solids and tapioca starch), fat (corn oil),minerals, and vitamins (Table I). When sufficient

milk is added to meet the patient's minimumrequirements for phenylalanine, the Lofenalacbase diet will provide the complete nutritionalsustenance for most infants with phenylketonu

na.Palatability is not a significant problem when

Lofenalac is administered by bottle to younginfants. However, when served in a cup, the childmay object to the pungent odor which is charactenistic of protein hydrolysates.

Phenylalanine-FreeProducts

Phenylalanine-free products have a distinctadvantage for the dietary management of olderchildren with phenylketonuria. They contain nophenylalanine and permit greater latitude inchoosing natural foods containing phenylalanineto meet the dietary requirement for this essentialamino acid. Therefore, these products serve theneeds of the older patient more effectively.

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LowMethio

NutrientLofenalac

(MJ)tPKUAid

(RL)tnineIsomil 3229-A 3200-AB

(RL) (MI) (MI)MSUDAid

(RL)Methionaid

(RL)321'XJ-K(MI)His@naid(RL)80056(MI)Calories454240516

40646024824246-4240486Protein

(gm)156012.5 20.31564.463.11461.20Fat

(gm)18028.1 6.8180019022.5CHO

(gm)60057.0 66 60

L-Amino Acids(gm)0060073.5EssentialIsoleucine0.752.60.56

1.080.8602.40.672.50Leucine1.416.11.02

1.70 1.760321.163.80Lysine1.576.10.77

1.851.917.16.00.875.80Methionine0.451.50.14

0.620.561.90.20.161.60Phenylalanine0.08<

0.070.6 0 <0.083.84.30.762.20Threonine0.774.80.51

0.930.653.33.20.523.10Tryptophan0.190.90.12

0.280.201.20.90.161.10Valine1.204.60.52

1.241.3803.20.713.10Histidine0.391.80.28

0.46 0.402.72.80.3400

Calcium(mg)4352,500650Minerals6344352,5002,5002,500700540Phosphorus(mg)3261,5004405083261,5001,5001,5001,500300

TABLE I

APPROXIMATE NUTRITIVE COMPOSITION OF SPECIAL DIETARY PRODUCTS°

NonessentialArginine0.343.10.830.680.395.14.40.964.60Alanine0.644.10.53NL0.767.15.60.605.90Aspartate1.348.11.295.151.6012.19.51.7210.60Cystine0.0251.50.150.340.0422.13.70.1071.80Glutamate3.789.32.481.854.3113.311.02.7612.30Glycine0.353.10.523.300.403.94.30.595.90Proline1.133.60.6NL1.132.31.60.681.90Serine1.024.80.68NL1.092.41.70.721.90Tyrosine0.816.00.400.93<

0.043.84.30.494.50GlutamineNLtNLNL4.75NLNLNLNLNL0

VitaminsVitaminA(IU)1,16002,2002,0301,160001,45001,440Vitamin

D(IU)2840340406284002900360Vitamin

E(IU)7.1012107.1007.200Vitamin

C(mg)3706053370038045Thiamin

(@Lg)4282,0000.56094382,0002,0004402,000450Riboflavin

(sg)7142,0000.61,0157142,0002,0007202,000540Vitamin

B5(@sg)2902,0000.55082902,0002,0003602,000360VitaminB12(;sg)1.420352.51.420201.8201.8Niacin

(;sg)5,71425,00098,1225,71425,00025,0005,80025,0007,200Folk,

acid(@Lg)724000.1251724004003040090Pantothenic

acid(;.tg)2,14220,00073,0462,14220,00020,0002,20020,0002,700Choline

(mg)6109486610062076Biotin

(;Lg)0.1330366006002260045Vitamin

K(;zg)7200.121027200710090Inositol

(mg)7200102722501007310090

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TABLE I (corcrlNuED)

APPR0xI MATE NUTRITIVE Cor@1PosITIoN OF SPECIAL DIETARY PRoDucTs'

Low

Met/noLofena!- nine MSUD Methio

ac PK [TAid Isoinil 3229-A 3200-AB Aid naid .3200-K Ilistinaid 80056Nutrient (MJ)t (RL)t (RL) (MI) (MI) (RL) (RL) (MI) (RL) (MI)

Magnesium (mg) 51 300 40 76 51 300 300 300 80 63

Iron (mg) 8.6 25 10 12 8.6 50 50 50 4 11Iodine (JLg) 32 150 120 66 32 150 150 150 60 41

Copper (pg) 429 2,500 500 609 429 2,500 2,500 2,500 500 540

Manganese (mg) 0.7 3.5 0 2 0.7 3.5 3.5 3.5 0.5 0.9

Zinc (mg) 2.9 15 4 4.1 2.9 15 15 15 0.9 3.6Sodium (mEiJ 9 61 10.4 10 9 61 61 61 34 3

Potassium (mEq) 12 66 10.4 18 12 66 66 66 19 9Chloride (mEq) 9 80 12.7 14 9 80 80 80 NL 4

°Per100 gm of powder.tMJ = Mead Johnson Company; RL = Ross Laboratories; NL = not listed.

PK U-aid@ is a hydrolysate of beef serum fromwhich phenylalanine has been removed; otheressential amino acids are present in satisfactory

amounts (Table I). The taste is different fromLofenalac, and this may hinder the change toPKU-aid. Appropriate dietary supplementationwith carbohydrate, fat, and some vitamins andminerals is necessary to provide nutritional requirements. There has been wide clinical expenience with its use, principally in Europe, under thetrade name Albumaid-XP.

Product 3229-A is not yet available commercially. It is a mixture of L-amino acids, vitamins,minerals, fat, and carbohydrate designed forfeeding the older patient with phenylketonuria.When reconstituted with water as directed, onepint of the product provides 400 kcal and containsthe daily requirements of vitamins, minerals, andamino acids—except phenylalanine—for a child 2years of age or older (Table I). Additional caloriesand the required phenylalanine can be met fromconventional foods given in prescribed amounts.The product has the characteristic bitter taste ofL-amino acid mixtures, but it is palatable whenflavored. Product 3229-A is currently undergoingclinical trials.

@Thisproduct is manufactured by Milner Scientific andMedical Research Company, LiVerpool, England, and will beavailable in the United States from Ross Laboratories,Columbus, Ohio 43216.

OTHER PRODUCTSAVAILABLEFORTREATMENT OF OTHER DISORDERS OF

- AMINO ACID METABOLISM

Maple Syrup Urine Diseaseand OtherBranched-Chain Aminoacidopathies

Dietary management of patients with maplesyrup urine disease (MSUD) and other branchedchain aminoacidopathies requires restriction inone or more of the three branched-chain aminoacids: leucine, isoleucine, and valine. Twoproducts are available.

MSUD-AID@ is a mixture of crystalline Lamino acids devoid of the branched-chain aminoacids. The powdered product which will beavailable in the United States will containminerals and water-soluble vitamins (Table I).Fat-soluble vitamins and additional calories fromcarbohydrate and fat are needed to meet generalnutritional requirements; additional protein isneeded as a minimal source for the branchedchain amino acids. Older children can receive anappropriately balanced mixture of natural foodsof known composition to meet nutritional requirements and enhance variety.

GIBCO@ amino acid mixes for treatment ofMSUD are mixtures of L-amino acids from whichthe branched-chain amino acids have been omitted. These mixtures provide nonoffending amino

§GrandIsland Biological Company, Grand Island, NewYork.

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acids in adequate amounts. Formulas consisting ofone of these amino acid mixtures plus a suitablesource of calories, minerals, and fat-soluble vitamins (e.g., Mead Johnson product 80056), supplemented with milk provides a complete diet forinfants with MSUD.

HereditaryTyrosinemia

Product 3200-AB is a hydrolysate low inphenylalanine and tyrosine used for dietarymanagement of patients with hereditary tyrosinemia in the first months of life. Although theprimary defect in this condition is still unknown,there is general agreement that dietary therapyameliorates the acute stage of the illness. Product3200-AB, manufactured by Mead Johnson, issimilar to Lofenalac (Table I) except that it is alsolow in tyrosine and phenylalanine. This productmeets the proposed standards for infant formula@as a complete food for infants when milk is addedto provide phenylalanine and tyrosine.

Homocystinuria

There are at least two types of homocystinuriacaused by cystathionine synthetase deficiency.

One form is amenable to pyridoxine therapy; theother requires a diet restricted in methionine andsupplemented with cysteine. Three products arecurrently available for dietary management of

homocystinuria.Methionaid@ is a methionine-free mixture of L

amino acids (Table I), water-soluble vitamins, and

minerals. Fat-soluble vitamins and additionalcalories from carbohydrate and fat must be addedto meet all necessary nutritional requirements.

Product 3200-K is a soy isolate infant formulalow in methionine (approximately 160 mg of Lmethionine per 100 gm of powder—Table I).When reconstituted according to the directions,product 3200-K meets the proposed standards forinfant formulas and provides sufficient methionine without supplementation for most children.The diet of the patient with cystathionine synthetase deficiency must contain sufficient cysteine topermit protein synthesis because cysteine hasbecome an essential amino acid under the condition of the mutation.

Low-Methionine Isomil: An additional lowmethionine, low-cysteine product containing carbohydrate, fat, protein, minerals, and vitamins(fat-and water-soluble)is availablefromRossLaboratories (Table I). When reconstituted

according to directions, it meets the proposedinfant formula standards, except for proteinwhich meets only minimum requirements forsulfur-containing amino acids. Palatability is the

same as the regular soy isolate protein formulaIsomil.

Histidinemia

HLstinaid@ is an L-amino acid mixture devoid ofhistidine and containing water-soluble vitaminsand minerals (Table I). When the powder is madeinto liquid form, Histinaid has similar qualities oftaste and smell to PKU-aid. Other foods must beadded to provide calories, fat-soluble vitamins,and essential fatty acids.

A low-protein diet of conventional foods canameliorate the degree of histidinemia. Dietsexceptionally low in protein present the risk ofoverrestriction of all amino acids and can lead toprotein deficiency and growth restriction. If thephysician elects to treat by restricting amino acidintake selectively, Histinaid is useful for thispurpose. The criteria for deciding to use a dietrestricted in histidine are not clear. When thistype of diet is used, the same managementprinciples apply as when other selectively deficient diets are used.

Other Products

When the primary treatment requires amixture of L-amino acids, it is helpful to have aseparate, premixed product as a source of allessential vitamins, minerals, and calories added inthe form of carbohydrates and fat.

Product 80056 is available from the MeadJohnson Company (Table I); it replaces Y-0192(caloric base) and Z-619 (mineral and vitaminmix). Product 80056 is a protein-free, vitaminmineral-fat-carbohydrate mixture for the provision of these nutrients in combination with theappropriate amino acid mixture.

Specific Amino Acid Mixes—A vitamin-mineral-calorie supplement can be combined with anappropriate amino acid mixture and limitedconventional foods for dietary management undermedical supervision. Experience has been gainedin this type of dietary formulation in metaboliccenters which provide such mixtures directly tothe family. This arrangement has the advantage ofbeing altered easily if a change is necessary; but,it has the disadvantage of being subject to error,as with any small-batch preparation.

Amino Acid Analogues—Recently keto- andhydroxy-analogues of branched-chain and otheramino acids have been used to treat clinicalconditions. The work of Walser et al.5 has shownthe capacity of these keto-analogues to sustainbody protein mass in patients with severe uremiawhile reducing the degree of uremia. Patientswith liver disease and hyperammonemia also have

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AgeNutrientUnitOto2

2to5mo mo6to12 nzolto2 yr2to3 yr3to4 yr4to6 yr6to8 yr8tolOyrCaloriestcal120/kg

110/kg1001,1001,2501,4001,6002,0002,200Volume

(H20)ml100/kg110/kg1001,1001,2501,4001,6002,0002,200Carbohydrate@gmCaloriesX

0.50ProteinsInfantsgm/kg1.8-2.2

1.8-2.01.8——————Childrengm/day——¿�—252530303540FatginCaloriesx

0.35SodiummEq/kg3

33333333PotassiuminEq/kg3

33333333Calciumtng400

500600700800800800800800Phosphorusmg200

4005007008008008009001,000Magnesiummg40

6070100150200200250250Ironmg61015151510101010Iodine25

404555607080100110Phenylalanine

Infantsmg/kg47-90 47-9025-47200@5001200-500@ -20O@5001200@5001200-5001200@5001Histidinemg/kg16-34

16-3416-34——————LeucineInfantsmg/kg76-150

76-15076-150750-1,000750-1,000750-1,000750-1,000750-1,000750-1,000Childrenmg/day——¿�——1,0001,0001,0001,0001,000

IsoleucineInfantsmg/kg79-11079-11050-75500-750500-750500-750500-750500-750500-750Childrenmg/day———1,0001,0001,0001,0001,0001,000ValineInfantsmg/kg65-10565-10550-80400-600400-600400-600400-600400-600400-600Methionine#Infantsmg/kg20-4520-4520-45——————Childrenmg/day---400-800400-800400-800400-800400-800400-800Cyst(e)ine°Infantsmg/kg15-5015-5015-50——————Childrenmg/day———400-800400-800400-800400-800400-800400-800

LysineInfantsmg/kg90-12090-12090-120——————Childrenmg/day———1,200-1,6001,200-1,6001,200-1,6001,200-1,6001,200-1,6001,200-1,600ThreonineInfantsmg/kg45-8745-8745-87——————Childrenmg/day———800-1,000800-1,000800-1,000800-1,000800-1,000800-1,000Tryptophan

Infantsmg/kg13-2213-2213-22——————Childrenmg/day———60-12060-12060-12060-12060-12060-120Vitamin

B,(thiamine)@tg

.2004005006006007008001,0001,100Vitamin

B.(riboflavin),ig4005006006007008009001,1001,200Vitamin

B,,(pyridoxine)2003004005006007009001,0001,200Vitamin

B@[email protected]

TABLE II

APPROXIMATE DAILY REQUIREMENTS FOR VARIOUS NUTRIENTS IN INFANCY AND CHILDHOOD°

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Folicacid@eg505010010020()Niacinmg57888

9 11

TABLE 11 (CONTINUED)

.3PPROXIMATE D@it.@' REQUIREMENTS FOR VARI@)US NUTRIENTS IN INI―AN(:v:\NI) CIIILI)UOOI)'

.%@(‘

0 to 2 2 to .5 6 to 12 1 to 2 2 to 3 -3 to 4 4 to 6 6 to 8 8 to 10

Nutrient Unit flU) iflO 1110 yr yr@ tjr tjr tjr yr

200 200 200 300

13

Vitamin C mg 35 35 35 40 40 40 40 40 40

Vitamin A IU 1,500 1,500 1,500 2,000 2,000 2,500 2,500 3,500 3,500

Vitamin D IU 400 400 400 400 400 400 400 400 400

Vitamin E IU 5 5 5 10 10 10 10 15 15

°Compiled from NAS/NRC RDA data and from amino acid data of Holt and Snyderman.°2 These dietary RDA have thelimitations of any statement of dietary requirement because of the individual variations a physician will encounter in workingwith a patient. This limitation is particularly true with amino acid requirements where amounts in excess of the requirement aretoxic. There is limited information on amino acid requirements of infants and children at different ages; the figures given here

are in excess of minimum requirements. Consequently, this table should be used only as a guide and should not be regarded as anauthoritative statement to which individual patients must conform.1@Thecaloricrequirementisincreasedwhenaproteinisprovidedasa mixtureof thecorrespondingfreeL-atninoacids.

@Minimum fraction is 50% of total calories; optimum value given.§Minimum fraction is 4% of total calories; optimum value given.¶Morephenylalanine (> 800 mg) is required in the absence of tyrosine.

@Moremethionine is required in the absence of cyst(e)ine.°°Morecyst(e)ine is required in the presence of a blocked trans-sulfuration outflow patl@@vayfor methionine tnetabolism.

shown improvement. This experience is too fragmentary to allow any projection of the clinicalusefulnessof these products at this time.

DELIVERY AND SUPERVISION OFDIETARY MANAGEMENT

Dietary management of the aforementioneddisorders of amino acid metabolism is most effective when the following dietary and therapeuticprinciples are carefully applied:

(1) The total nutrient composition of the

special dietary product is considered so theproduct provides not only all the amino acidrequirements except the implicated amino acid(s),but also trace mineral, vitamin, and other micronutrient requirements. For the infant, the specialdiet often also meets total caloric needs. Thetarget amino acid is added from milk or other Selected foods. After infancy, conventional foodsprovide calories, any micronutrient not adequately provided by the special product, and theproper amount of the target amino acid.

(2) Conventional foods are used as part of thediet for children after infancy. In constructing adiet of special formula and conventional foods,the information in the National Academy ofScience report° on recommended dietary allowances (RDA) is useful as a guide (Table II).However, the RDA is designed to assure an

adequate aniount of any nutrient to virtually allthe population on an average day. As stated in thereport, rigidity in applying the guidelines canlead to an unpalatable or unwieldy diet.

(3) Diet is selected with consideration of thepatient's needs and expectations. The composition of conventional foods, as provided in standard tables of food composition,― is important inassuring a balanced diet when special products

and conventional foods are presented. The physician and dietitian should select foods that meetnutritional requirements, provide a varied andpalatable diet, and consider the child's preferences.

(4) The child's actual dietary intake, his growthand nutritional status, blood values for the implicated amino acid, and other tests for nutritionalsufficiency are monitored periodically.

(5) These services are initiated and maintainedby the child's private physician in consultationwith a metabolic centeE. Children treatedwithout assistance from the experienced staff incenters usually run an added risk. A list of centersequipped and willing to assist in care is includedin the Appendix.

Caution is needed when using special dietaryproducts to treat disorders of amino acid metabolism because of the genetic individuality andparticular nutritional needs of each patient.Preparation of specific diets from synthetic or

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semisynthetic products in combination withnatural foods is best done by experienced people.The treatment of many patients with hereditaryaminoacidopathies is being guided by centerswhere there is expertise in handling metabolicdisorders. These regional networks offer consultation and special services to the pediatricians andpatients. Children with hereditary disorders ofamino acid metabolism are encountered infrequently in most pediatricians' practices, butenough patients exist to justify regionalization oftreatment programs and development of specialresources when a large population (2 to 10million) is found in one area.

The value of reclassifying the special dietaryproducts as “¿�foods―has been noted. The marketto supply the consumers with special needs issmall and there is little economic incentive forindustry to develop improved products, Also,there is a need to improve the taste and smellproperties of the products, but resources to meetthis need are lacking.

RECOMMENDATIONS ANDCONCLUSIONS

The Committee on Nutrition endorses theproposals of the Subcommittee on Amino AcidModified Diets to:

(1) Maintain and periodically publish a list ofmetabolic centers. The centers listed in theAppendix have volunteered to (a) provide consultative services, (b) provide dietary surveillance,(c) monitor nutritional status and treatment, and(d) provide dietary supplies on an emergencybasis to physicians who request them for patientswith hereditary disorders of amino acid metabolism.

(2) Maintain up-to-date information onproducts for treating these disorders; this information would be available through the metaboliccenters.

Continue consultations with manufacturers andthe FDA to bring about technical improvement ofproducts and better regional distribution ofthem.

(4) Initiate discussion within the AmericanAcademy of Pediatrics, and at federal, state, andcommunity levels to bring about improvedfunding and operation of nutritional servicesprovided by metabolic centers treating patientswith hereditary disorders of amino acid metabolism.

SUMMARY

A sufficient variety of semisynthetic dietaryproducts is now available to permit control of

amino acid imbalance in several inborn errors ofmetabolism. However, they must be used carefully, and their effects monitored closely.Continuing development of products for this typeof special diet—to provide a wider variety—isnecessary.

Regionalization of treatment programs forpatients with inborn errors of metabolism isrecommended. Metabolic centers which areaccumulating experience and have good laboratory support may be the most efficient way ofproviding adequate treatment for patients withinborn errors of metabolism.

COMMITTEE ON NUTRITION

MALCOLM A. HOLLIDAY, M.D., ChairmanARNOLD S. ANDERSON, M.D.

LEwIS A. BARNE5S, M.D.GILBERT B. FORBES, M.D.RICHARD B. GOLDBLOOM, M.D.JAMESHAWORTH,M.D.MARY JANE JESSE, M.D.ALVIN M. MAUER, M.D.

CHARLES R. SCRIVER, M.D.

MYRON WINICK, M.D.

Consultants0. L. KLINE, M.D.ROBERT W. MILLER, M.D.ROBERT W. WINTERS, M.D.

SUBCOMMITEE ON AMINO ACIDMODIFIED DIETS

MALCOLM A. HOLLIDAY, M.D., ChairmanJOGINDERCHOPRA,M.D.MARTHA M. FREEMAN, M.D.DONOUGH O'BRIEN, M.D.CHARLES R. SCRIVER, M.D.

SELMA SNYDERMAN, M.D.

ConsultantPARVIN JUSTICE, Ph.D.

REFERENCES1. Committee on Nutrition: Nutritional management in

hereditary metabolic disease. Pediatrics 40:289,1967.

2. Fine SD (Associate Commissioner for Compliance):Letter to manufacturers, June 6, 1972.

3. 21CFR, part 125.5: Label statements concerning dietaryproperties of food purporting to be or representedfor special dietary uses.

4. 21CFR, part 125.5: Label statement relating to infantfood.

5. Committee on Nutrition: Commentary on breastfeeding and infant formulas, including proposedstandards for formulas. Pediatrics 57:278, 1976.

6. Alexander FW, Clayton BE, Delves HT: Mineral andtrace-metal balances in children receiving normaland synthetic diets. Q J Med 43:89, 1974.

7. Clow CL, Reade TM, Scriver CR: Management ofhereditary metabolic disease: The role of alliedhealth personnel. N Engl J Med 284: 1291, 1971.

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APPENDIXNamesof Directorsand Addressesof MetabolicCentersThat Have VolunteeredServicesas Described

8. Walser M, Coulter AW, Dighe S. Crantz FR: The effectof ketoanalogues of essential amino acids in severechronic uremia. J Clin Invest 52:678, 1973.

9. Food and Nutrition Board, National Research Council:Recommended Dietary Allowances, ed 8. Washington DC, National Academy of Science, 1974,pp 1-130.

10. Watt BK, Merrill AL (eds): Composition of Foods.Washington DC, Department of Agriculture,Handbook No. 8, 1963.

11. Holt LE, Snyderman SE: The amino acid requirementsof infants. JAMA 175:100, 1961.

12. Holt LE, Snyderman SE: The amino acid requirements

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the High Risk Infant. New York, John Wiley & Sons,1975, section 6, pp 405-475.

RICHARD J. ALLEN, M.D.

Director, Pediatric Neurology UnitUniversity of MichiganAnn Arbor,Michigan48104(313-763-4101)

STANLEY Bmu.ow, M.D.

Diagnostic and Treatment UnitUniversity of WisconsinMental Retardation Center2304 University AvenueMadison, Wisconsin 53706(608-263-1656)

NEIL BUIST, M.D.

Department of PediatricsUniversity of Oregon Medical CenterPortland, Oregon 97201(503-225-8392)

A. M. DIGEORGE, M.D.St. Christophers Hospital2600 North LawrencePhiladelphia, Pennsylvania 19133(215-427-5179)

GEORGE DONNELL, M.D.

Children's Hospital of Los Angeles4650 Sunset BoulevardLos Angeles, California 90027(213-663-3341)

LOUIS J. EL5A5, II, M.D.

Director, Division of Medical GeneticsDepartment of Pediatrics, Box 23344Emory University School of MedicineAtlanta, Georgia 30322(404-377-2411)

STEVE GOODMAN, M.D.

B. F. Stolinsky Research LaboratoriesDepartment of PediatricsUniversity of Colorado Medical Center4200 East Ninth AvenueDenver, Colorado 80220(303-394-7430 or 7301)

Moiuy W. HAYMOND,M.D., andRICHARD E. HILLMAN, M.D.

Department of PediatricsSt. Louis Children's Hospital500 South KingshighwaySt. Louis, Missouri 63110(314-367-6880)

NEIL HOLTZMAN, M.D.

Pediatric Genetic UnitDivision of Human GeneticsJohns Hopkins UniversityBaltimore, Maryland 21205(301-955-3054)

R. RODNEYHOWELL,M.D.P.O. Box 20708Texas Medical CenterHouston, Texas 77025(213-526-8431)

HARVEY L. LEVY, M.D.

Massachusetts Metabolic DisordersScreening ProgramForest HillsBoston, Massachusetts 02130(617-522-3702)

Pm-ER [email protected]@s, M.D.Director, Pediatric MetabolismDepartment of PediatricsMedical College of Virginia1200 East Broad StreetRichmond, Virginia 23298(804-770-3033)

OWEN M. RENNERT, M.D.

Department of Pediatrics, Biochemistryand Neuroscience

University of FloridaCollege of MedicineGainesville, Florida 32610(904-392-3331)

JOSEPHD. SCHULMAN,M.D.

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RONALD Scorr, M.D.

Department of PediatricsUniversity of WashingtonSchool of MedicineSeattle, Washington 98105(206-543-3370)

CHARLES R. SCRIVER, M.D.

The McGill UniversityMontreal Children's Hospital2300 Tupper StreetMontreal 108,Quebec, Canada(514-937-8511)

J. R. SEELY,M.D.Children's HospitalUniversity of OklahomaP.O. Box 26901Oklahoma City, Oklahoma 73190(405-271-5509)

CAROL SHEAR, M.D.

Department of Pediatrics

University of Miami School of MedicineMiami, Florida 33136(305-547-6853)

SELMA E. SNYDERMAN, M.D.

New York UniversitySchool of Medicine550 First AvenueNew York, New York 10016(212-679-3200)

ROBERT A. ULSTROM, M.D.

Professor of PediatricsDepartment of Pediatrics1460 Mayo Memorial BuildingMinneapolis, Minnesota 55455(612-373-8170)

[email protected]@s H. WHARTON,M.D., andMs. HELENBERRYChildren's Hospital Medical CenterElland and Bethesda AvenueCincinnati, Ohio 45229(513-559-4451)

PAUL W. K. WONG, M.D., M.Sc.

Director, Division of Human GeneticsDepartment of PediatricsRush-Presbyterian-St. Luke's Medical Center1753 West Congress ParkwayChicago, illinois 60612(312-942-6298)

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1976;57;783Pediatrics Parvin Justice

Chopra, Martha M. Freeman, Donough O'Brien, Charles R. Scriver, Selma Snyderman andWInters, Subcommitee on Amino Acid Modified Diets, Malcolm A. Holliday, Joginder

Mauer, Charles R. Scriver, Myron Winick, O. L. Kline, Robert W. Miller, Robert W.Gilbert B. Forbes, Richard B. Goldbloom, James Haworth, Mary Jane Jesse, Alvin M.

Committee on Nutrition, Malcolm A. Holliday, Arnold S. Anderson, Lewis A. Barness,Special Diets for Infants With Inborn Errors of Amino Acid Metabolism

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1976;57;783Pediatrics Parvin Justice

Chopra, Martha M. Freeman, Donough O'Brien, Charles R. Scriver, Selma Snyderman andWInters, Subcommitee on Amino Acid Modified Diets, Malcolm A. Holliday, Joginder

Mauer, Charles R. Scriver, Myron Winick, O. L. Kline, Robert W. Miller, Robert W.Gilbert B. Forbes, Richard B. Goldbloom, James Haworth, Mary Jane Jesse, Alvin M.

Committee on Nutrition, Malcolm A. Holliday, Arnold S. Anderson, Lewis A. Barness,Special Diets for Infants With Inborn Errors of Amino Acid Metabolism

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