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Introduction
Fatty acids are a primary metabolic fuel for the body when fasting is prolonged and a direct source of
energy for heart and skeletal muscle. Ketones such as acetoacetate and -hydroxybutyrate, obtained
during hepatic fat metabolism, are an important energy source for the brain in particular, as well as
other tissues. Infants and young children may have problems adapting to fasting due to their high
basal energy needs required to maintain body temperature; the high rate of brain metabolism; and the
low activity of several enzymes involved in energy production (42).
During fasting, fatty acids are released from adipocytes and carried to other tissues by lipoproteins
or albumin. Fatty acids with > 10 carbons are activated to-CoA esters in the cytosol. These acyl-CoA
compounds are carried to the mitochondria by carnitine palmitoyl transferase types I and II (CPT I
and II). Fatty acids with < 10 carbons do not require CPT I and II to enter the mitochondria, where they
are activated to-CoA esters (42).
In the mitochondria, fatty acids are degraded by the sequential removal of 2-carbon fragments as
acetyl-CoA (Figure R). Four carbon chain length-specific enzymes are required: an acyl-CoA
dehydrogenase, an enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and a 3-ketoacyl-CoA
thiolase (Figure R). In the liver, most of the acetyl-CoA is used for ketone body synthesis (42).
Deficiencies of very long-chain-, long-chain-, medium-chain-, short-chain-, 3-hydroxy-, and shortchain-hydroxyacyl-CoA dehydrogenases and mitochondrial trifunctional protein (51, 54) have been
reported. Medium-chain-acyl-CoA dehydrogenase deficiency (MCADD) was found to occur in about
1/8,900 live births in Pennsylvania (63). Similar initial symptoms are found in all the dehydrogenase
deficiencies. Some patients may develop symptoms as neonates. Symptoms are often induced by
fasting or an infection with vomiting or diarrhea. Lethargy, muscle weakness, seizures, coma, and
death may occur. Fatty infiltration of organs is often found on autopsy (37, 42).
Substrate
Acyl -CoA
Chemical structure
Enzyme
Enoyl -CoA
3-Hydroxyacyl -CoA
NADH 2
3-Ketoacyl -CoA
Acetyl -CoA
II.
III.
Establish Diagnosis
A. The Defect (24, 42, 46, 52-54, 62)
1. Disorders of mitochondrial FAO may result from 1 of several defects:
a. Very-long-chain-acyl-CoA dehydrogenase deficiency.
b. Long-chain-acyl-CoA dehydrogenase deficiency.
c. Long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency.
d. Medium-chain-acyl-CoA dehydrogenase deficiency.
e. Short-chain-acyl-CoA dehydrogenase deficiency.
f. Short-chain-hydroxyacyl-CoA dehydrogenase deficiency.
g. Mitochondrial trifunctional protein deficiency.
B. Differential Diagnosis (44, 58, 59)
1. Infants or children who, on fasting, have episodes of arrhythmias (4), lethargy, vomiting,
hepatomegaly, or Reye-like syndrome, seizures, cardiomyopathy, peripheral neuropathy,
pigmentary retinopathy, or coma associated with any of the following laboratory findings
should have a diagnostic work-up for FAO defect:
a. Hypoketotic hypoglycemia.
b. Minimal metabolic acidosis.
c. Elevated blood urea nitrogen (BUN) concentration.
d. Elevated blood ammonia concentration.
e. Elevated plasma urate concentration (11).
f. Elevated concentration of transaminases.
g. Myoglobinuria (13).
h. Plasma carnitine deficiency.
i. Dicarboxyluria.
j. Rhabdomyolysis (43).
2. Siblings of children who have died with sudden infant death syndrome (SIDS) or Reye's
syndrome should be evaluated for FAO defect (11, 21, 35, 42).
3. See references 5, 9, 17-19, 28, 31, 42, 51, and 57 for methods of diagnosis to determine
which defect is present.
IV.
V.
VI.
Establish Prescription
A. Energy
1. Prescribe amount that should support normal weight gain for infants and children and maintain
appropriate weight for height in adults (Table 20-1, p 359).
2. Requirements vary widely.
Warning:
Inadequate energy intake will result in growth failure in infants and children,
weight loss in adults, and can adversely affect metabolic control if catabolism
of fat stores occurs (27).
B
Protein
1. Prescribe amount that supplies 10-12% of total energy (Table 20-1, p 359).
C. Fat (44)
1. Prescribe amount of total fat that promotes goals of nutrition support (10, 16).
a. Very-long chain and long-chain-FAO defects:
1) Prescribe ~30% of energy as fat.
2) About 50% of fat energy should be derived from MCT and remainder from fats that
supply linoleic and -linolenic acids (20, 34).
3) Docosahexaenoic acid may be essential for the patient with long-chain-3-hydroxyacylCoA dehydrogenase deficiency.
i. Harding, et al (20) suggest 65 mg/day for children < 20 kg and 130 mg/day for
children > 20 kg.
b. Medium- and short-chain-FAO defects:
1) Provide 15-25% of total daily energy as fat (7, 33).
c. Prescribe 3% of total energy as linoleic acid and 1.0% as -linolenic acid.
Warning:
EFA deficiency may occur if intakes of linoleic acid and -linolenic acid are
inadequate. Symptoms include dermal scaliness and increased skin
permeability, reduced growth rate, renal abnormalities, increased erythrocyte
fragility, increased susceptibility to infections, and decreased rate of
development (26, 40, 50).
D. Carbohydrate
1. Prescribe remaining energy as carbohydrate.
E. Fluid
1. Prescribe amount that will supply water requirements (Table 20-1, p 359). 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 (2).
2. Requirements may be higher than recommended secondary to accompanying fever.
F. L-Carnitine
1. Prescribe amount that maintains normal plasma free carnitine concentration > 30 mol/L.
2. Amounts of 50 to 150 mg/kg have been suggested (41, 46).
3. Efficacy of carnitine supplementation in treatment of FAO defects is debated but use is almost
standard therapy.
G. Glycine
1. Supplement diet with 100 to 200 mg/kg/day (41).
H. Riboflavin
1. Supplement diet with 100 to 200 mg/day, if beneficial (12, 26).
I.
Fasting
1. Instruct parents, patient, or caretakers to prevent infants from fasting > 4 hours, children
> 6 hours, and adults > 8 hours.
2. Raw cornstarch (1.75-2.5 g/kg) helps prevent hypoglycemia (8).
Warning:
Increased frequency of feeding, tube feedings, and IV glucose may be
necessary if patient is febrile, has diarrhea, or is vomiting.
3. Supply 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), sugar (48 kcal/Tbsp), or
pured or table foods containing little or no fat (Tables 20-2 and 20-4, pp 359 and 360).
a. Do not use corn syrup or table sugar for infants because of osmolarity they yield (28).
b. Do not use honey for infants because it may contain botulinum toxin (50).
4. Add beikost or table foods after infant is 3 to 4 months old or is developmentally ready to
provide variety in taste, color, and texture (Table 20-2, p 359).
5. If additional carbohydrate is needed, see Table 20-4, p 360.
D. L-Carnitine (Appendix 26, p A-28)
1. Add liquid L-carnitine to ProViMin medical food mixture.
2. L-carnitine tablets may be used if patient is old enough to swallow them.
E. Glycine (Appendix 26, p A-28)
1. Weigh GLY on scale that reads in grams.
2. Add sufficient boiled, cooled water to yield 100 mg/mL. (eg, 10 g GLY to yield 100 mL).
3. Store in refrigerator for 1 week, if not frozen.
4. Measure into medical food mixture with disposable syringe.
F. Riboflavin (Appendix 26, p A-28)
1. Have parents or patients finely crush number of tablets required to supply prescribed
milligrams of riboflavin if patient cannot swallow tablets.
2. Mix with medical food mixture.
3. Give 25 to 30 mg with each feed. Additional will not be absorbed. A greater amount is
absorbed when given with food than when fasting.
G. Fluid and Mixing Instructions for ProViMin
1. Boil bottles, nipples, rings, and mixing utensils for 5 minutes and cool. Boil more water for
5 minutes, then cool to room temperature.
2. Measure or weigh specified boiled, cooled water, ProViMin, fat, carbohydrate, L-carnitine,
GLY, and riboflavin into clean containers.
3. Pour about 1/2 specified volume of boiled, cooled water into clean blender. Running blender
at slow speed, gradually add ProViMin and fat and blend for at least 15 seconds.
4. Dissolve powdered carbohydrate in part of the water and pour into blended ProViMin and
infant formula mixture, add boiled, cooled water to yield final prescribed volume, mix well, and
pour into opaque sterilized nursing bottles or cups. Prepared formula not used immediately
should be refrigerated and used within 24 hours. Shake well before feeding.
5. Do not use microwave oven to warm formula. Unevenly heated formula can burn infants and
steam can make bottles explode.
6. Discard formula remaining in bottle or cup after feeding.
7. Store unopened cans at room temperature. Cover opened can of ProViMin and store in dry
place (not in refrigerator). Use within 1 month after opening.
8. Notify parents or caretakers when they may discontinue use of aseptic technique in making
formula.
F. Diet Guide
1. Provide parents, caretakers, or patient with completed Diet Guide (Table 20-5, p 361) with
each diet change.
Warning:
Never permit patient to fast > 4 hours if infant, > 6 hours if child, or > 8 hours
if adult; shorten fasting time if patient is febrile, has diarrhea, or is vomiting.
2. Check diet to determine if it supplies Recommended Dietary Intakes (RDIs) of minerals and
vitamins (Table 6-4, p 118, and Appendices 13 and 14, pp A-14 to A-15).
a. Appendix 23, p A-25, may be used to check adequacy of nutrients if computer program is
not available.
b. If ProViMin mixture provides < 100% of RDIs for infants and < 75% for children,
supplement diet with needed minerals and vitamins if not provided by beikost or table
foods and laboratory tests indicate need (Appendix 11, p A-10, for composition of
supplements).
B. Osmolarity
1. If concentration of prescribed medical food mixture is > 27 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 ProViMin powder is 2.74 mosm.
2. If osmolarity is > 450 mosm/L for infants, > 750 mosm/L for children, > 1,000 mosm/L for
adults (30, 48), or is 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 > 27 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 (47).
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.
X.
Sample Prescription
A. Establish and fill prescription for 2 month-old infant weighing 5.2 kg who has LCHAD deficiency
using Recommended Daily Nutrient Intakes from Table 20-1, p 359, and nutrient contents from
Table 20-2, p 359, and Appendix 9, p A-9.
1. Establish prescription.
Energy
Fat
120 kcal/kg x
624 kcal x
Docosahexaenoic acid
5.2 kg
0.30
=
=
624 kcal
187 kcal
338 mg
20.8 g
18.7 kcal
2.1 g
65 mg
5.2 kg
Linoleic acid
624 kcal
0.03
-Linolenic acid
MCT oil
624 kcal
0.01
6.2 kcal
187 kcal
0.50
93.5 kcal
8.2
11.4 g
Protein
624 kcal
0.12
74.9 kcal
18.7 g
Fluid
L-Carnitine
145 mL/kg x
50 mg
x
5.2 kg
5.2 kg
=
=
0.69 g
2. Fill prescription.
Medical Food Mixture
Measure
Fat
(g)
ProViMin
25.6 g
Soy oil
10.4 mL
Polycose Powder
96 g
MCT oil
12.3 mL
Add water to make 754 mL (25 fl oz).
0.37
9.40
0.0
11.30
Linoleic -Linolenic
Acid
Acid
(g)
(g)
0.00
4.78
0.00
0 00
0.00
0.73
0.00
0.00
MCT
Protein
Energy
(g)
(g)
(kcal)
0.37
0.00
0.00
11.30
18.7
0.0
0.0
0.0
80
84
365
94
21.07
4.78
0.73
11.67
18.7
623
Total per day
29
6.90
1.05
15
11.98
Percentage of energy
Approximate osmolarity of medical food mixture is < 300 mosm/L. Estimated potential renal solute load
is < 200 mosm.
B. Example 2
Establish and fill prescription for newborn weighing 3.5 kg who has MCADD using Recommended
Daily Nutrient Intakes from Table 20-1, p 359, and nutrient content from Table 20-2, p 359, and
Appendix 9, p A-9.
1. Establish prescription.
Energy
Fat
120 kcal/kg
420 kcal
x
x
3.5 kg
0.25
Protein
420 kcal
Fluid
L-Carnitine
Glycine
Riboflavin
150 mL/kg
50 mg
100 mg
200 mg
x
x
x
=
=
420 kcal
0.12
3.5 kg
3.5 kg
3.5 kg
=
=
=
=
2. Fill prescription.
Medical Food Mixture
Measure
ProViMin
Glycine
Soy oil
Polycose Liquid
16.9 g
350 mg
13 mL
132 mL
Fat
(g)
0.2
0.00
11.7
0.0
Protein
(g)
12.4
0.00
0.0
0.0
Energy
(kcal)
53
0.0
103
264
XI.
TABLE 20-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With a
Mitochondrial FAO Defect
Age
Nutrient
1
Protein
(% of energy)
Infants
0 to < 3 mo
3 to < 6 mo
6 to < 9 mo
9 to < 12 mo
10 - 12
10 - 12
10 - 12
10 - 12
(g/day)
Energy1
(kcal/kg)
Fluid2
(mL/kg)
150 - 125
160 - 130
145 - 125
135 - 120
(mL/day)
23
4 to < 7 yr
30
1,300 - 2,300
7 to < 11 yr
1,650 - 3,300
1,500 - 3,000
900 - 1,800
34
Women
11 to < 15 yr
46
15 to < 19 yr
46
1,200 - 3,000
19 yr
1,400 - 2,500
50
Men
11 to < 15 yr
45
2,000 - 3,700
15 to < 19 yr
59
2,100 - 3,900
19 yr
63
2,000 - 3,300
TABLE 20-2. Average Nutrient Contents of Gerber Baby Foods (Beikost), ProViMin , and MCT Oil1
Food
Measure
Fat
(g)
Protein
(g)
Energy
(kcal)
1 Tbsp2
1 Tbsp2
0.17
0.07
0.35
0.16
15
10
0.04
0.00
0.00
93.30
0.67
2.00
0.04
0.10
0.19
0.07
0.00
1.58
73.00
0.19
12
10
16
765
14
312
6
1
2
3
1 Tbsp
1 Tbsp2
1 fl oz
100 mL
2
1 Tbsp
100 g
1 Tbsp2
TABLE 20-3. Exchange Lists for Nutrition Support of Children and Adults With Mitochondrial FAO Defects 1
Food List
Measure
Fat
(g)
Protein
(g)
Energy
(kcal)
Meat, lean
1 oz
3.0
55
1 oz
1.0
35
1 cup
0.5
90
Fat 3
varies
5.0
45
Fruit
0.0
0.0
0
0
60
80
Starch/Bread
varies
25
trace
Vegetable
1/2 cup cooked, or 1 cup raw
0.5
2
25
1
Exchange Lists for Weight Maintenance. Chicago: The American Dietetic Association, 1995.
2
From reference 38.
3
Care must be taken to select fats that provide adequate linoleic and -linolenic acids, such as those high in canola or
soybean oil.
Measure
Energy
(kcal)
Carbonated beverages
Corn syrup
Fruit and juice drinks
Hard candy
Jam, jelly
Jell-O
Polycose Glucose Polymers, liquid
Polycose Glucose Polymers, powder
Popsicles , frozen juice bars
Slush Drinks (ie, Mr. Misty )
Syrup
4 fl oz
1 Tbsp
4 fl oz
3 pieces, approx
1 Tbsp
1/4 cup, prepared
1 fl oz
2 Tbsp
1/2 cup
3 fl oz
1 Tbsp
60
57
60
60
50
65
59
45
50
60
55
Day
Diagnosis:
Year
Birthdate: __________/_________/__________
Mo
Day
Age:
Year
Medical Food
Weight:
Amount
ProViMin
L-carnitine
mg
Glycine
mg
Riboflavin
mg
Skim milk
cups
(kg/lb)
Fat
Protein
Energy
(g)
(g)
(kcal)
Tbsp/Exchanges
Cereals/Starch/Bread
Cereals: With Fruit
Desserts, low fat
Fruits/Juices
Meats, lean
Vegetables
____________________________________________________
Nutritionist
Hospital Number:
Day
Physical Data
Laboratory Data
(cm)
(kg)
(cm)
Diagnosis:
Year
(mol/L)
Plasma Carnitine
Total
Free
(mol/L)
(mol/L)
Triene/
Tetraene
Ratio
Blood
Glucose
Ferritin
Albumin
Hgb
(mg/dL)
(ng/mL)
(g/dL)
(g/dL)
Fat
(g)
Linoleic Acid
(%)
(g)
(%)
-Linolenic
Acid
(g)
(%)
(mg)
(g)
(kcal)
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