PROTOCOL 24 Urea Cycle Disorders

Nutrition Support of Infants, Children, and Adults With

CYCLINEX -1 and CYCLINEX -2 Amino Acid-Modified Medical Foods

I. Introduction
Disorders of the urea cycle result from inherited defects in any one of six enzymes which function in
urea production (Figure T). With the exception of ornithine transcarbamylase (OTC) deficiency, all
have an autosomal recessive mode of inheritance. OTC deficiency is inherited as an X-linked
dominant trait that is often lethal in males (3,4, 8, 9).
Ammonia is normally converted to urea in the liver through the Krebs-Henseleit cycle (Figure T)
and excreted in urine. The first three enzymes of the cycle and N-acetylglutamate synthetase (NAGS)
are mitochondrial. NAGS catalyzes conversion of acetyl-CoA plus glutamate to N-acetylglutamine, an
essential cofactor for carbamylphosphate synthesis. Carbamylphosphate synthetase (CPS) catalyzes
conversion of ammonia, ATP, and bicarbonate to carbamylphosphate. OTC utilizes
carbamylphosphate and ornithine (ORN) as cosubstrates to form citrulline (CIT). CIT is exported from
mitochondria to the cytoplasm where cytosolic reactions are linked to those three mitochondria
functions. CIT and aspartate form argininosuccinic acid, in a reaction catalyzed by argininosuccinic
acid synthetase (AS). Fumarate is cleaved from argininosuccinic acid by argininosuccinic acid lyase
(AL), yielding arginine (ARG). Urea is then formed by the action of arginase, regenerating cytosolic
ORN which is transported back into the mitochondria to react with OTC (3, 4, 8, 9).

Restrict Prevent (N) Therapeutic phenylacetate

Serine tissue protein Glutamine
dietary (N)
protein catabolism
Folate
(N)
Phenylacetylglutamine Urine
(N)
+
Glycine (N) (NH4) + CO2
Therapeutic
N-acetylglutamate Acetyl-CoA + Glutamate
benzoate
Carbamylphosphate
N-acetylglutamate Oxaloacetate
synthetase
synthetase
Hippurate (N)
Orotic
Carbamylphosphate acid

L-citrulline L-aspartate
Urine

Ornithine Argininosuccinate
= Site of enzyme defect transcarbamylase synthetase
(N) = nitrogen

L-ornithine L-argininosuccinate

Argininosuccinate
Urea Arginase lyase

L-arginine
Urine
Therapeutic L-arginine
Fumarate

Figure T. Nitrogen metabolism in urea cycle enzyme defects.

Hyperammonemia is a biochemical manifestation of all disorders of the urea cycle. Other

biochemical characteristics of each defect follow: CPS deficiency causes decreased plasma CIT
concentration; OTC deficiency results in orotic aciduria and X-linked patterns of transmission;
418 Urea Cycle Disorders 2001 Ross Products Division
 AS deficiency is associated with increased plasma CIT concentration accompanied by orotic aciduria;
AL deficiency causes increased argininosuccinate in plasma and urine; and arginase deficiency results
in increased ARG concentration in plasma and urine. Clinical features in the newborn suggestive of
urea cycle enzyme defects occur with protein ingestion or infection with body protein catabolism. In
increasing order of severity, these defects include poor feeding, vomiting, lethargy, hypotonia, stupor,
bleeding diatheses, convulsions, coma, shock, and death (19). Mental retardation occurs in survivors
of these newborn episodes (3,4, 8, 9, 52). Orthoptic liver transplantation has been successfully used
for patients with CPS and OTC deficiencies (9). Retroviral-mediated gene therapy is being studied in
AS-deficient cell cultures (12). Tamura, et al (50) found that glucagon enhanced urea excretion in AS
deficiency.

II. Outcome of Nutrition Support

Results of therapy in infants with complete or near complete enzyme deficiencies have been less than
optimal with delayed death and below normal development. If serious brain swelling and coma are
prevented in the neonatal period or if onset of disease expression is delayed, physical growth and
mental development are more nearly normal with nutrition and pharmacologic support. If diagnosis is
anticipated and treatment is begun during the early neonatal period in affected siblings with
citrullinemia or argininosuccinic aciduria (ASA), relatively normal outcome is observed, even in the
severe enzyme defects (33, 34, 37, 41, 43). Females heterozygous for OTC deficiency may expire
during the neonatal period (19), may develop coma during the postpartum period (15, 55) or if
parenteral nutrition is administered (15), or may be developmentally delayed if untreated (17, 33, 42).
A female with arginase deficiency was reported to develop coma on the first day of her menstrual
period and spontaneously recover 3 days later (22).

III. Establish Diagnosis

A. The Defect
1. Hyperammonemia may result from a defect in any of the following enzymes:
a. NAGS (10, 23).
b. CPS.
c. OTC.
d. AS.
e. AL.
f. Arginase - plasma ammonia may be normal in some instances.
B. Diagnostic Studies
1. Diagnostic studies should be conducted in any person with the following symptoms:
a. Poor feeding, vomiting, lethargy, hypotonia, spasticity, irritability, twitching, seizures,
apnea or coma.
b. Plasma ammonia concentration > 150 mol/L in newborn period and > 80 mol/L
thereafter (3).
2. See references 3, 4, and 8-10 for methods of diagnosis.
3. Other causes of inherited hyperammonemia must be ruled out, including the following:
a. Abnormalities of fatty acid metabolism (Protocol 20).
b. Transport defects of urea cycle intermediates - lysinuric protein intolerance (Protocol 11),
and hyperornithinemia-hyperammonemia-homocitrullinemia syndrome (Protocol 23).
c. Organic acidurias (Protocols 5, 6, 10, 13, 18, 20).
4. Causes of acquired hyperammonemia that must be ruled out include the following:
a. Deficient ARG supply.
b. Reye's syndrome.
c. Transient hyperammonemia of newborn.
d. Valproate therapy (31, 38, 45).
Warning: Laboratory results MUST be available within 4 to 8 hours when a disorder of
urea cycle enzyme is suspected as hyperammonemia is a metabolic
emergency.

IV. Rationale for Nutrition Support

A. Correct Primary Imbalance in Metabolic Relationships
1. Restrict dietary protein to amount tolerated without causing hyperammonemia (5).

2001 Ross Products Division Urea Cycle Disorders 419

 2. Prevent excessive body protein catabolism (5).
3. Restrict dietary tryptophan to that required for growth to prevent excess synthesis of serotonin
(25) and quinolinic acid (6).
B. Provide Alternate Metabolic Pathways (28)
1. Prescribe L-ARG or L-CIT as indicated.
2. Prescribe sodium benzoate, sodium phenylacetate or sodium phenylbutyrate to help decrease
accumulated toxic precursors.
C. Supplement "Conditionally Essential" and Essential Nutrients
1. Supply L-ARG (20) (except in arginase deficiency), L-carnitine (39), L-cystine, and L-tyrosine
in adequate amounts (30).
2. Administer N-carbamylglutamate to patients with deficiency of NAGS or CPS (29).
3. Use essential amino acid mix to supply approximately 50% of prescribed protein.

V. Establish Goals of Nutrition Support

A. Plasma Amino Acid Concentrations (53)
1. Maintain 2- to 4-hour postprandial plasma concentrations of selected amino acids in following
ranges or within normal range for age established in laboratory used.
Amino Acid mol/L mg/dL Reference
ARG 100 -150 1.75 -2.60 1
Aspartic acid (ASP) 14 - 50 0.18 - 0.67 36
CIT 30 - 128 0.52 - 2.24 36
Glutamine 335 - 755 4.90 - 11.04 36
Glycine (GLY) 100 - 170 0.75 - 1.28 36
Serine (SER) 100 - 170 1.05 - 1.79 36
2. In practice, obtaining blood 2 to 4 hours postprandially is not always possible. Acceptable local
standards should be developed if plasma amino acids are evaluated at other times (Practical
Aspects of Nutrition Support, p viii).
B. Plasma Ammonia Concentration (3-5, 53)
1. Maintain plasma ammonia concentration < 35 mol/L or within normal range for age
established in laboratory used.
C. Growth, Development, and Nutrition Status
1. Support normal growth rate in infants and children and maintain appropriate weight for height
in adults.
2. Support normal development.
3. Maintain normal nutrition status.
a. Prevent ARG deficiency (20).
b. Prevent hyperlipidemia.
c. Prevent catabolism.
d. Prevent orotic aciduria in deficiencies of AL, AS, and OTC (3-6).
D. Behavior and Neurologic Status
1. Prevent anorexia (25).
2. Maintain normal neurologic status.
E. Physical Manifestations
1. Prevent liver disease (30).

VI. Establish Prescription

A. L-ARG
1. Prescribe L-ARG for patients who have deficiency of either AL or AS. Do not prescribe for
patients with arginase deficiency.
a. Becomes essential amino acid in most disorders of the urea cycle (13)
b. Enhances waste nitrogen excretion.

420 Urea Cycle Disorders 2001 Ross Products Division

 2. Requirements vary:
a. From patient to patient, depending on age, extent of enzyme defect, and plasma ARG
concentration
b. In most cases, amount prescribed is between 400 and 700 mg/kg (8, 9).
B. L-CIT
1. May be used instead of L-ARG in CPS or OTC deficiencies
2. Initially, prescribe 170 mg/kg (8, 9),
3. Amount to prescribe depends on:
a. Age.
b. Extent of enzyme defect.
c. Plasma CIT concentration
C. Citrate
1. Patients with treated AS and AL deficiencies have been found to have very low citrate
excretion (3).
2. Some clinicians prescribe 2.2 to 3.0 mmol/kg per 24 hours (3, 26).
3. Greater amounts may be required during periods of illness accompanied by fever.
D. Protein (13, 48)
1. Prescribe amount that promotes goals of nutrition support (Table 24-1, p 429).
2. Amount prescribed may need to be increased if sodium benzoate, sodium phenylacetate, or
sodium phenylbutyrate is administered daily.
Warning: Inadequate protein intake will result in failure to thrive in infants; weight loss,
low plasma transthyretin concentration, osteopenia, and hair loss in children
and adults; and may result in hyperammonemia (51).
E. N-Carbamylglutamate (10, 23)
1. Patients with deficiency of NAGS or CPS may not require protein restriction if
N-carbamylglutamate is administered.
2. Administer 80 to 100 mg/kg daily.
3. L-ARG supplements and drugs used to enhance waste nitrogen may be unnecessary when
N-carbamylglutamate is administered.
F. Energy
1. Prescribe amount greater than Recommended Dietary Allowances (RDAs) (9) to prevent
catabolism (3, 4) (Table 24-1, p 429).
2. Requirements will vary widely and may be 5%-10% greater than those listed in Table 24-1,
p 429, when infection or hyperammonemia is present.
Warning: Inadequate energy intake will result in low plasma transthyretin
concentration, poor growth in infants and weight loss in children and adults,
decreased dietary protein tolerance, and increased body protein catabolism
causing hyperammonemia.
G. Fluid
1. Prescribe amount that will supply water requirements (Table 24-1, p 429). Under normal
circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL fluid to children and
adults for each kcal ingested (7).

H. Cyanocobalamin, Niacin, Folate, Pantothenic Acid, Pyridoxine

1. Sodium benzoate.
a. Enhances waste nitrogen excretion through conjugation of GLY with benzoic acid to form
hippuric acid (18).
b. GLY biosynthesis and conjugation of GLY with benzoate require adequate cellular
concentrations of cyanocobalamin, niacin, folate, pantothenic acid, and pyridoxine (56).
c. Prescribe vitamins listed above at 3 to 5 times Recommended Dietary Intakes (RDIs) for
age (Appendices 13 and 14, pp A-14 and A-15) when sodium benzoate is administered.

2001 Ross Products Division Urea Cycle Disorders 421

 2. Sodium phenylacetate and sodium phenylbutyrate.
a. Phenylacetic acid conjugates with glutamine in the liver (1) and with glutamine or taurine
in kidney (28) and enhances excretion of waste nitrogen as phenylacetylglutamine.
b. Cyanocobalamin, niacin, folate, and pantothenic acid are required for conjugation
reactions (56).
c. Prescribe vitamins listed above at 3 to 5 times RDIs for age (Appendices 13 and 14,
pp A-14 and A-15) when phenylacetate or phenylbutyrate is administered.

VII. Fill Prescription (4)

A. L-ARG or L-CIT (Appendix 26, p A-28)
1. Solutions of L-ARG and L-CIT
a. Mix weighed amounts of L-ARG and L-CIT with boiled, cooled water to make know
volumes of each to yield 100 mg/mL (eg, 100 g of L-ARG or L-CIT with enough water to
make 1 liter).
b. Measure into Cyclinex mixture with disposable syringe.
c. Refrigerate in sterilized, closed containers until used. Discard unused suspensions after
1 week, if not frozen.
d. Shake well before using.
Warning: Use only ARG-free base.
B. Citrate
1. When citrate is prescribed, Polycitra K Oral Solution may be used.
2. May be ordered from:
Baker Norton Pharmaceuticals, Inc.
8800 NW 36th St
Miami, FL 33178-2404
Phone: 800 735-2315.
C. N-Carbamylglutamate
1. Administer 1/4th to 1/8th of prescribed dose before each feed, depending on number of feeds.
2. May be ordered from:
Curtin & Warner
19 Phoenix Place
Lewis, East Sussex, UK
D. Protein
1. Calculate amount of infant formula with iron (use until 1st birthday), beikost, whole cow's milk,
or table foods (Table 24-2, p 429) required to fill approximately 50% of the protein
prescription.
a. See Servings Lists for PHE-Restricted Diets (Protocol 1, pp 13-26) for portion sizes.
2. Subtract amount determined above from total protein prescription.
3. Supply any remaining prescribed protein with Cyclinex (Table 23-2, p 429).
a. Cyclinex-1 is for infants and toddlers and Cyclinex-2 is for children, adolescents, and
adults.
b. Weigh Cyclinex powder on scale that reads in grams because of variability of household
measuring equipment (Practical Aspects of Nutrition Support, p vii) and changes in
density during shipping.
c. See Table 22-4 (p 402, footnote 3) for approximate packed weight of Cyclinex powder in
level, dry US standard household measures.
E. Energy
1. Calculate energy provided by infant formula, beikost, whole cow's milk, or table foods and
Cyclinex (Table 24-2, p 429) required to fill protein prescription.
2. Subtract amount determined above from total energy prescription.
3. Provide any remaining prescribed energy with Polycose Glucose Polymers powder
(23 kcal/Tbsp, 3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9); Pro-Phree Protein-Free
Energy Module With Iron, Vitamins and Minerals (Appendix 11, p A-10), sugar (48 kcal/Tbsp),
or Free Foods B (Table 24-2, p 429), depending on age of patient.
a. Do not use corn syrup or table sugar for infants because of osmolarity they yield (35).
422 Urea Cycle Disorders 2001 Ross Products Division
 b. Do not use honey for infants because it may contain botulinum toxin (49).

F. Fluid and Mixing Instructions

1. Add sufficient boiled, cooled water to infant formula, Cyclinex, and carbohydrate (if needed) to
yield prescribed volume. Tap water may replace boiled, cooled water when preparing Cyclinex
for older infants, children, and adults.
2. Mix with sterilized blender at lowest speed for no longer than 3 to 4 seconds. Excess mixing
may destabilize emulsion. May also be mixed in sterilized, tightly closed container by
shaking vigorously for 10 to 12 seconds.
3. Refrigerate in sterilized, closed containers until used. Discard unused portion 24 hours after
mixing because of nutrient loss.
4. Do not use terminal sterilization or boil because of Maillard reaction (Practical Aspects of
Nutrition Support, p viii).
5. Warm or cool medical food mixture to room temperature before feeding to infants. Shake
mixture well before feeding.
6. Do not warm medical food mixture for infants in microwave oven. Unevenly heated formula
can burn infants, and steam can make bottles explode.
7. Notify parents or caretakers when they may discontinue using aseptic technique in preparing
medical food mixture for infants.
8. For children and adults, chill Cyclinex medical food mixture to improve taste.
G. Cyanocobalamin, Niacin, Folate, Pantothenic Acid, Pyridoxine (Appendix 26, p A-28)
1. Prescribe daily supplement, if needed.
2. See Appendix 11, p A-10, for composition of supplement.
3. Folate requires prescription.
H. Sodium Benzoate, Sodium Phenylacetate, Sodium Phenylbutyrate (Appendix 26, p A-28)
1. Administer appropriate amount with each feed or 1/6th to 1/8th daily dose with each meal,
depending on number of meals fed daily.
I. Diet Guide
1. Provide parents, caretakers, or patient with completed Diet Guide (Appendix 22, p A-24) with
each diet change.
2. Feed young infants 6 to 8 times daily (24, 44).
3. Feed older infants, children, and adults 4 to 6 times daily (24, 44).

VIII. Evaluate Adequacy and Safety of Planned Nutrition Support

A. Nutrient Adequacy
1. Determine if diet provides nutrients in amounts prescribed in Section VI, Establish
Prescription, p 420.
a. See Table 24-2, p 429, for composition of Cyclinex, infant formulas, beikost, and whole
cow's milk.
2. Check diet to determine if it supplies RDIs of minerals and vitamins (Appendices 13 and 14,
pp A-14 and A-15).
a. See Table 22-4, p 402, for composition of Cyclinex and Appendices 4 through 7, pp A-4 to
A-7, for complete nutrient composition of infant formulas.
b. Appendix 23, p A-25, may be used to check adequacy of nutrients if computer program is
not available.
c. If Cyclinex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
supplement diet with needed minerals and vitamins if laboratory tests indicate need
(Appendix 11, p A-10, for composition of supplements).
B. Osmolarity
1. If concentration of prescribed medical food mixture is > 24 kcal/fl oz, determine if osmolarity
is in acceptable range.
a. Determine osmolarity by laboratory analysis or use mathematical formula given in
Appendix 18, p A-20.
b. Osmolarity per gram of Cyclinex is listed in Appendix 19, p A-21.

2001 Ross Products Division Urea Cycle Disorders 423

 2. If osmolarity is > 450 mosm/L for infants (32), > 750 mosm/L for children, > 1,000 mosm/L for
adults (47), or greater than tolerated by patient, increase water content of prescribed medical
food mixture and recalculate its osmolarity.
C. Potential Renal Solute Load
1. Dehydration will result if renal solute load is greater than renal-concentrating ability of patient.
2. If concentration of medical food mixture prescribed is > 24 kcal/fl oz, estimate its potential
renal solute load.
a. This step is important to prevent dehydration of infants who may have renal-concentrating
capacity as low as 600 mosm/L.
b. Upper limit of renal solute load for neonates is approximately 1,100 mosm/L (46).
3. A method for estimating potential renal solute load is given in Appendix 20, p A-22.
4. If potential renal solute load is excessive, increase water content of medical food mixture and
recalculate.

IX. Suggested Evaluation of Nutrition Support

A. Plasma Amino Acid Concentrations (21)
1. Initial.
a. Evaluate twice weekly by quantitative methods until plasma concentrations normalize to
prevent deficiency.
2. Ongoing.
a. Frequent evaluations help ensure adherence to nutrition support plan.
b Evaluate every 2 to 3 months when patients condition is stable.
3. Unacceptable plasma amino acid concentrations.
a. If any plasma amino acid concentration is below lower limit of normal noted in Section V,
Establish Goals of Nutrition Support, p 420, and patient has ingested full protein
prescription:
1) Increase prescribed Cyclinex by 10% and reevaluate plasma concentrations in 3 to
7 days.
2) If any amino acid continues below its lower limit of normal, repeat above process until
value is in treatment range.
b. If any plasma GLUNH2 concentration is greater than upper limit of normal noted
Section V, Establish Goals of Nutrition Support, p 420, and patient has ingested full
prescription:
1) Decrease prescribed amount of protein from natural foods by 10% and reevaluate in
3 days.
2) If GLUNH2 concentration continues above its upper limit of normal, repeat above
process until value is in treatment range.
4. Elevated plasma GLUNH2 concentrations may indicate impending hyperammonemia.
a. Obtain 3-day diet diary.
b. Evaluate for infection.
c. Obtain plasma ammonia concentration.
d. If no infection is present, protein intake is not greater than prescribed, and energy intake is
adequate, decrease prescribed protein by 10% and reevaluate plasma glutamine
concentrations in 3 days.
e. Repeat above process until ammonia and GLUNH2 concentrations are in treatment ranges.
B. Plasma Ammonia Concentration (36)
1. Initial.
a. Evaluate daily until concentration is in normal range.
2. Ongoing.
a. Evaluate weekly until patient is 6 months old, twice monthly until 1 year of age, and
monthly thereafter if patient is well.
3. Elevated plasma ammonia concentration (36).
a. Obtain 3-day diet diary and evaluate patient for infection. If no infection is found, protein
intake is not greater than prescribed, and energy intake is not less than prescribed:

424 Urea Cycle Disorders 2001 Ross Products Division

 1) Decrease protein from natural foods by 10% or increase prescribed sodium benzoate,
sodium phenylacetate, or sodium phenylbutyrate by 10% (if not already at upper limit
tolerated) and reevaluate plasma ammonia concentration in 1 to 2 days.
2) If plasma ammonia concentration remains above upper limit of normal, repeat
process until normal concentration is achieved.
Warning: Over-restriction of protein and/or energy will result in increase in plasma
ammonia concentration.
C. Protein Status
1. Evaluate plasma transthyretin concentration monthly until patient is 1 year of age and every
3 months thereafter (Appendix 17, p A-18, for standards).
a. Plasma transthyretin concentrations provide a more reliable and rapid indication of protein
status than plasma albumin concentrations.
b. Plasma albumin concentrations may be in the normal range when plasma transthyretin
concentrations show a clear deficiency (2).
2. If plasma transthyretin concentration is below standard:
a. Increase prescribed protein by 10% and reevaluate plasma transthyretin concentration in
1 month.
b. If plasma transthyretin concentration continues below standard, repeat above process until
value is in normal range.
c. Evaluate plasma ammonia and plasma GLUNH2 concentrations with each increase in
prescribed protein.
3. If GLY deficiency is suspected, verify by measuring pyroglutamic acid in urine (27).
a. Urinary pyroglutamic acid excretion > 325 mol/mmol creatinine suggests GLY deficiency.
4. If protein catabolism is suspected, verify by measuring 3-methylhistidine in urine.
a. Urinary 3-methylhistidine excretion > 25 mol/mol creatinine suggests catabolism.
D. Iron Status
1. Plasma ferritin concentration.
a. Evaluate at 6, 9, and 12 months of age and every 6 months thereafter (Appendix 17,
p A-18, for standards).
b. If plasma ferritin concentration is below standard:
1) Increase iron intake to 4 mg/kg with supplements (ferrous sulfate).
2) Evaluate plasma ferritin concentration monthly on increased iron intake.
3) Continue iron supplements until plasma ferritin concentration is in normal range.
2. Complete blood count.
a. Hemoglobin and hematocrit concentrations should be evaluated at 6, 9, and 12 months of
age and every 6 months thereafter (Appendix 17, p A-18, for standards).
b. Normal heme synthesis requires adequate GLY.
E. Plasma Sodium and Potassium Concentrations
1. Plasma sodium concentration.
a. If sodium benzoate, sodium phenylacetate, or sodium phenylbutyrate is prescribed,
evaluate after each prescription change.
2. Plasma potassium concentration
a. If Polycitra K Oral Solution is used, evaluate on a routine basis.
F. Growth Status
1. Length/height and weight.
a. Measure monthly to 1 year, every 3 months until prepubertal growth spurt is completed,
and every 6 months thereafter. Plot measurements on NCHS growth charts.
b. Maintain length/height and weight between 10th and 90th percentiles. Some normal
infants, children, and adults will fall above or below these percentiles.
2. If length/height or weight falls below usual growth channel:
a. Increase prescribed protein and energy by 5% to 10% and remeasure in 1 month.
b. If length/height or weight remains low, repeat above process until usual growth channel is
achieved.
c. Evaluate plasma ammonia and GLUNH2 concentrations with each increase in prescribed
protein.
2001 Ross Products Division Urea Cycle Disorders 425
 G. Nutrient Intake
1. Maintain records of food intake for 3 days immediately before each blood test (Appendices 24
and 25, pp A-26 and A-27).
2. Evaluate intakes of protein and energy before each blood test.
3. Evaluate mineral and vitamin intakes after each diet change.
a. Appendix 23, p A-25, may be used to check adequacy of nutrients if computer program is
not available.
b. See Appendix 28, p A-29, for information about ordering software for diet evaluation.
H. Clinical Summary
1. A summary record of growth, laboratory, and nutrient intake data is useful for patient
management (Table 24-3, p 430).

X. Sample Prescription
A. Example 1
Establish and fill prescription for male neonate weighing 3.0 kg who has OTC deficiency using
Recommended Daily Nutrient Intakes from Table 24-1, p 429, and approximate nutrient contents
from Table 24-2, p 429.
1. Establish prescription.
L-CIT 350 mg X 3.0 kg = 1,050 mg/day
Protein 2.2 g/kg x 3.0 kg = 6.6 g
Energy 150 kcal/kg x 3.0 kg = 450 kcal
Fluid 160 mL/kg x 3.0 kg = 480 mL
Vitamin B supplements, if indicated
Citrate
2. Fill prescription.
Medical Food Mixture Measure L-CIT Protein Energy
(mg) (g) (kcal)
Cyclinex-1 44 g 0 3.3 224
Similac With Iron Ready to Feed 236 mL 0 3.3 160
L-CIT 1 10.5 mL 1,050 0.0 0
Polycose Liquid 33 mL 0 0.0 66
Add water to make 480 mL (16 fl oz).

Total per day 1,050 6.6 450

Total per kg 150 2.2 150
Approximate osmolarity of medical food mixture is < 400 mosm/L. Estimated potential renal solute
load is < 110 mosm.
1
Solution is 100 mg/mL.

B. Example 2
Establish and fill prescription for 24-month-old child weighing 13.0 kg who AS deficiency using
Recommended Daily Nutrient Intakes from Table 24-1, p 429, and approximate nutrient contents
from Table 24-2, p 429.

426 Urea Cycle Disorders 2001 Ross Products Division

 1. Establish prescription.
L-ARG 7,150 mg /day
Protein 13 g
Energy 1,365 kcal
Fluid 1,495 mL
Vitamin B supplements, if indicated
Citrate
2. Fill prescription.
Medical Food Mixture Measure ARG Protein Energy
(mg) (g) (kcal)
Cyclinex-1 87 g 0 6.5 444
1
L-ARG 72 mL 7,200 0.0 0
Polycose powder 34 g 0 0.0 129
Add water to make 710 mL (24 fl oz). Offer additional water ad libitum daily.

Food List Servings

Breads/Cereals 3 --- 1.8 90
Fats 3 --- 0.3 180
Fruits 4 --- 2.0 240
Vegetables 4 2.0 40
Free Foods A 2 0.4 130
Free Foods B 2 0.0 110
Total per day 7,200 13.0 1,363
Approximate osmolarity of medical food mixture is < 450 mosm/L. Estimated potential renal solute load
is < 110 mosm.
1
Solution is 100 mg/mL.

C. Example 3
Establish and fill prescription for 7-year-old girl weighing 25.0 kg who has CPS deficiency using
Recommended Daily Nutrient Intakes from Table 24-1, p 429, and approximate nutrient contents
from Table 24-2, p 429.
1. Establish prescription.
L-CIT 8,750 mg /day
Protein 17 g
Energy 1,730 kcal
Fluid 2,125 mL
Vitamin B supplements, if indicated
Citrate

2001 Ross Products Division Urea Cycle Disorders 427

 2. Fill prescription.
Medical Food Mixture Measure CIT Protein Energy
(mg) (g) (kcal)
Cyclinex-2 57 g 0 8.6 51
1
L-CIT 87.5 mL 8750 0.0 0
Sugar 60 g 0 0.0 240
Add water to make 710 mL (24 fl oz). Offer additional water ad libitum daily.

Food List Servings

Breads/Cereals 5 0 3.0 150
Fats 8 0 0.8 480
Fruits 7 0 3.5 420
Vegetables 3 0 1.5 30
Free Foods A 3 0 0.3 195
Total per day 8,750 17.7 1,766
Approximate osmolarity of medical food mixture is < 500 mosm/L.

XI GLY, GLUNH2, Protein, and Nitrogen Deficiencies

A. GLY Deficiency
1. Decreased heme synthesis (27).
2. Decreased glutathione synthesis (27).

B. GLUNH2
1. Decreased purine and pyrimidine biosynthesis.

C. Protein
1. Kwashiorkor (51).

D. Nitrogen
1. No weight gain, decreased weight gain, or weight loss (48).
2. Impaired nitrogen retention (48).
3. Protein malnutrition (48).

XII. Nutrition Support During Febrile Illness or Following Trauma

A. Rationale
1. In normal persons, febrile illness and trauma are accompanied by catabolism of body protein
(54).
2. See references 3, 8, 9, and 13 for management.
Warning: Prolonged use (> 2 days) of protein-free or low-energy diet will lead to protein
catabolism and rebound hyperammonemia.
B. Contraindicated Medication
1. Valproate (31, 38, 45).

428 Urea Cycle Disorders 2001 Ross Products Division

TABLE 24-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With Urea
Cycle Disorders

Age Nutrient
1-3
Protein Energy 1 Fluid 4
(g/kg) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 2.20 - 1.25 150 - 125 160 - 130
3 to < 6 mo 2.00 - 1.80 140 - 120 160 - 130
6 to < 9 mo 1.80 - 1.60 130 - 115 150 - 125
9 to < 12 mo 1.60 - 1.40 120 - 110 130 - 120

(g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 8 - 12 945 - 1,890 945 - 1,890
4 to < 7 yr 12 - 15 1,365 - 2,415 1,365 - 2,415
7 to < 11 yr 14 - 17 1,730 - 3,465 1,730 - 3,465

Women
11 to < 15 yr 20 - 23 1,575 - 3,150 1,575 - 3,150
15 to < 19 yr 20 - 23 1,260 - 3,150 1,260 - 3,150
19 yr 22 - 25 1,785 - 2,625 1,785 - 2,625

Men
11 to < 15 yr 20 - 23 2,100 - 3,885 2,100 - 3,885
15 to < 19 yr 21 - 24 2,200 - 4,095 2,200 - 4,095
19 yr 23 - 32 2,625 - 3,465 2,625 - 3,465
1
From references 14, 16.
2
From reference 13, 16.
3
Protein intake may need to be increased if sodium benzoate, sodium phenylacetate, or sodium phenylbutyrate is
prescribed.
5
From reference 7. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL fluid to
children and adults for each kcal ingested.

TABLE 24-2. Serving Lists for Protein-Restricted Diets: Approximate Nutrient Content per Serving

Food List Nutrient

Protein Energy
(g) (kcal)
Breads/Cereals 0.6 30
Fats 0.1 60
Fruits 0.5 60
Vegetables 0.5 10
Free Foods A 0.1 65
Free Foods B 0.0 55
1
Alimentum Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 1.86 68
Cyclinex-1 , 100 g 7.50 510
Cyclinex-2 , 100 g 15.00 440
1
Isomil Soy Formula With Iron, Ready to Feed, 100 mL 1.66 68
1
Similac With Iron Infant Formula, Ready to Feed, 100 mL 1.40 68
2
Whole cow's milk, 100 mL 3.39 63
1
See Appendices 4 through 7, pp A-4 to A-7, for complete nutrient composition of infant formulas.
2
From reference 40. See Appendix 8, A-8, for complete nutrient composition.

2001 Ross Products Division Urea Cycle Disorders 429

430 Urea Cycle Disorders
TABLE 24.3. Urea Cycle Disorders Clinical Summary Sheet
Name: Hospital Number:

Date of Birth: __________/__________/__________

Mo Day Year

Date Age Physical Data Laboratory Data Nutrient Intake Data

1
Length/ Weight Head ARG ASP CIT GLUNH2 GLY SER Ammonia Hgb Hct Ferritin Trans- TAG ARG CIT Protein Energy
Height Circum thyretin
(mo/d/yr) (yrs/mo) (cm) (kg) (cm) (mol/L) (mol/L) (mol/L) (mol/L) (mol/L) (mol/L) (mol/L) (g/dL) (%) (ng/mL) (mg/dL) (mg/dL) (mg) (mg) (g) (kcal)
2001 Ross Products Division

1
Triacylglycerols
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