Phenotype

Clinical Symptoms

(prior to treatment)

Biochemical

% BCKD activity

Classical

Neonatal onset, poor feeding, lethargy, altered tone, ketoacidosis, seizures. Symptoms often present prior to learning NBS results. Prenatal testing in at-risk siblings can allow dietary intervention at birth. Nearly all due to mutations in the E1 BCKD subunits

↑↑ allo-ILE, BCAA, BCKA

0 -2

Intermediate

Failure to thrive, ketoacidosis and developmental delay; classical symptoms can occur during catabolic illness/stress

↑ allo-ILE, BCAA, BCKA

3 - 30

Intermittent

Normal early development, episodic ataxia/ketoacidosis, severe symptoms may be precipitated by catabolic illness/stress. May be missed by MS/MS NBS

Normal BCAA, BCKA when asymptomatic

5 - 20

Thiamin (B1) responsive

Similar to intermediate. Often due to mutations in E2 BCKD subunit

↑ allo-ILE, BCAA, BCKA ↓BCKA and/or BCAA with thiamin therapy

2 - 40

Lipamide dehydrogenase deficiency

Normal neonatal period, failure to thrive, hypotonia, lactic acidosis, developmental delay, movement disorder. Due to mutations in the E3 BCKD subunit - a component of both pyruvate dehydrogenase and α-ketoglutarate dehydrogenase

Moderate BCAA and BCKA, ↑ α-ketoglutarate, pyruvate

0 - 25

Laboratory test/symptom

Symptomatic

Pre-symptomatic/treated

MS/MS NBS on blood spot

↑↑BCAA, especially LEU;

LEU:PHE ratio > 4.5-5

<24 hr of age : normal or slight ↑BCAA;

> 24 hr of age : slight ↑to ↑BCAA

Treated in good control: normal or slight ↑BCAA

Plasma amino acids

↑↑BCAA (especially LEU), allo-ILE present; without TX, VAL and ILE may become normal or low. As LEU increases, see decreases in other essential and non-essential AA

normal or slight ↑BCAA; allo-ILE present

Urine DNPH Rx

++ after day 2-3 of life

-

Urine organic acid analysis

↑BCKA

normal or slight ↑

Ketonuria (urine keto sticks)

++

-

Ammonia

May be ↑ or ↑↑

-

BCKD activity

0-3%

0-3%

Blood glucose

↓ or normal

normal

Weight

↓

normal

Lethargy, intermittent apnea, opisthotonus

+

-

Maple syrup odor (in urine)

+ usually by 72+ hr, (first apparent in cerumen by 12-24 hr)

-

Irritability, poor feeding

+

-

Vomiting

+

-

Ataxia

+

-

Visual hallucinations

+

-

Coma, respiratory failure by 7-10 days of life without treatment

+

-

Nutrient

Recommendation

Source

LEU

Sufficient intake to allow adequate protein synthesis for growth, repair and health maintenance and to achieve LEU levels in recommended treatment range.

LEU allowance is also dependent on residual BCKD activity, age, weight, sex, life stage and health of the individual with MSUD.

In the newborn, the recommended intake is: 40-100 mg LEU/kg/day

• Intact protein (PRO)

In infants: breast milk or infant formula with known LEU content

In children and adults: foods such as fruits/vegetables, some grains/cereals that are typically low in protein and for which there is known LEU content

PRO

DRI ¹

Plus additional 20-40% if an amino acid-based medical food is used

• Intact PRO (as above)
• BCAA-free medical food

VAL, ILE

VAL and ILE are essential amino acids and may need to be supplemented when BCAA are restricted to achieve appropriate LEU blood levels. To promote anabolism of LEU, when LEU blood levels are high, additional supplementation of VAL and ILE is often required

• Intact PRO
• Supplemental VAL, ILE²

KCAL

DRI ¹

• Intact PRO
• BCAA-free medical food
• Free foods ³
• Modified low PRO food ⁴

Other nutrients, minerals and vitamins ⁵

DRI ¹

• Intact PRO
• BCAA-free medical food
• Supplemental nutrients, vitamins and minerals ⁶

NUTRIENT

AGE

LEU

mg/kg

ILE

mg/kg

VAL

mg/kg

PROTEIN

g/kg

ENERGY

kcal/kg

FLUID

ml/kg

0 to 6 mo

40-100

30-90

40-95

2.5-3.5

95-145

125-160

6 to 12 mo

40-75

30-70

30-80

2.5-3.0

80-135

125-145

1-3 yr

40-70

20-70

30-70

1.5-2.5

80-130

115-135

4-8 yr

35-65

20-30

30-50

1.3-2.0

50-120

90-115

9-13 yr

30-60

20-30

25-40

1.2-1.8

40-90

70-90

14-18 yr

15-50

10-30

15-30

1.2-1.8

35-70

40-60

19 yr +

15-50

10-30

15-30

1.1-1.7

35-45

40-50

Ref

Trimester

Total protein (g/kg body weight)

Intact protein (g/kg body weight)

BCAA-free protein (g/kg body weight)

F.102

Pre-pregnancy

1.0 – 1.2 g

0.6 – 0.8 g

0.4 g

First trimester

1.2 g

0.6 g

0.6 g

Second trimester

~

0.8 g¹

~

Postpartum

~

1.0 g

~

F.78

First trimester

1.1 g

0.1 g

0.9 g

Second trimester

1.5 g

0.4 g

1.1 g

Third trimester

1.1 g

0.4 g

0.8 g

Diagnosis (Problem)

Related to (Etiology)

As evidenced by

(Signs and Symptoms)

INTAKE (NI)

Excessive energy intake NI 1.5

Inadequate energy intake NI 1.4

Inadequate intake from enteral nutrition NI 2.3

Excessive intake from enteral nutrition NI 2.4

Inadequate fat intake NI 5.6.1

Excessive fat intake NI 5.6.2

Excessive protein intake NI 5.7.2

Inappropriate intake of (specify amino acids) NI 5.7.3

CLINICAL (NC)

Impaired nutrient utilization NC 2.1

Altered nutrition-related lab values NC 2.2

BEHAVIORAL (NB)

Food and nutrition-related knowledge deficit NB 1.1

Limited adherence to nutrition-related recommendations NB 1.6

Limited access to food NB 3.2

Other

Excessive intake of (specify food or beverage)

Poor appetite due to (specify metabolic disorder)

Nutrition prescription no longer meeting energy needs

Nutrition prescription exceeding energy needs

Protein restriction necessitated by MSUD

LEU, VAL, and ILE restriction necessitated by MSUD

Metabolic disorder (MSUD)

New diagnosis of MSUD

Lack of adequate insurance coverage to pay for special metabolic formulas

Lack of adequate insurance coverage to pay for low-protein foods

Other

BMI (or weight-for-height) >97^th percentile

BMI (or weight-for-height) >85^th percentile

BMI (or weight-for-height)

< 3^rd percentile

(specify weight change) weight gain/loss over the past (specify time frame)

EFA deficiency

Dietary recall

Altered lab values (specify)

Elevated amino acids (specify)

Reports of higher than recommended amino acid intake (specify)

Abnormal newborn screen

Lack of appreciation for the importance of making nutrition-related changes

Presentation to clinic for initial nutrition education

Denial by insurance company to provide payment

Other

METABOLICALLY STABLE INDIVIDUALS WITH MSUD

Clinical Statement

(Item # on survey)

RD % Agreement

n=11

MD % Agreement n=6

Notable Comments

Discussion Points for Consideration

Agreement Rating (1-7)

Mean +/- SD

Protein Recommendation

Meeting the age-appropriate DRI for protein (sum of amino acids in medical food and intact protein) is sufficient for individual with classical MSUD (21)

18

(82% disagree)

100

1 MD and 4 RDs indicated they give more (up to 30%), especially when source is metabolic formula

Large discrepancy between RD and MD

3.9 +/- 1.9

Low agreement rating

The protein equivalent in only the medical food should be used to determine adequacy of dietary protein intake of an individual with classical MSUD (22)

27

(73% disagree)

0

(100% disagree)

Discrepancy between RD and MD

2.8 +/- 1.6

Strong disagreement

Recommendation for the amount of protein in the diet should be above the DRI when the majority of protein is provided in the form of protein equivalent from free amino acids (23)

82

67

RD Labs should also be guide

5.2 +/- 1.6

Recommendation for the amount of protein in the diet should be based on ideal body weight for age (24)

55

(36% disagree)

83

(17% disagree)

6 RDs indicate actual weight used if normal weight range and IBW if underweight

Discrepancy between RD and MD

4.8 +/- 1.4

Low agreement rating

Fluid Requirements

Infants weighting up to 10 kg: 100 ml/kg body weight (25a)

82

83

5.6 +/- 1.4

Children 11-20 kg: 1000 ml + 50 ml for every kg over 10 kg body weight (25bb)

82

83

5.6 +/- 0.9

Children >20 kg: 1500 ml + 50 ml for every kg over 10 kg body weight (25c)

82

67

5.2 +/- 1.3

Adults: 30-45 ml/kg body weight (25d)

82

83

RD fluid ad lib if eating well and stable

5.5 +/- 0.8

Additional fluid should be provided when consuming a hyperosmotic medical food mixture (32)

91

100

RD If total fluid is within guidelines and no GI problems then would not add

6.0 +/- 0.8

BCAA Supplementation

If plasma ILE or VAL are below desired range, they should be supplemented by using solution/pre-weighed powders of these the L-amino acids added to a BCAA-free medical food (26)

100

83

MD may need supplement even if "normal". 2 RD also try increasing natural protein in diet

5.9 +/- 0.8

ILE and VAL may be supplemented using LEU-free medical food (e.g., I-Valex) in combination with BCAA-free medical food (27)

46

50

2 MDs and 3 RDs lack of flexibility, can't titrate

ILE and VAL separately

4.4 +/- 1.4

Low agreement

Energy Recommendation

Meeting the age-appropriate DRI for energy should be sufficient for individuals with classical MSUD (28)

82

100

5 RDs adjust based on weight, growth, metabolic control and protein-sparing

5.5 +/- 1.0

When to Consume

Medical food should be prescribed to consume at least 3 times/day (29)

100

100

6.2 +/- 0.6

Medical food without BCAA and intact protein with BCAA should be prescribed to be consumed together to enhance anabolism (30)

73

83

RD some patients find this difficult because full after medical food

5.8 +/- 1.1

Vitamin/Mineral Supplements

Should be provided to well individuals if not consuming recommended amount of medical food or if medical food choice does not provide DRI for all vitamin/minerals (31)

100

100

6.6 +/- 0.5

Timing of Blood Samples

Blood samples for plasma amino acid analysis should be taken 2 or more hr after food/medical food consumption (33)

82

67

MD get them when we can

3 RDs impractical, random captures full variation of amino acid levels

5.5 +/- 1.4

Blood samples for plasma amino acid analysis should be taken in morning before food/medical food consumption (34)

36

(27% disagree)

50

(33% disagree)

6 RDs try for consistent times

RD morning sample could help determine baseline AA levels

4.2 +/- 6.8

Low agreement

Monitoring

Plasma transthyretin should be used as most reliable indicator of recent protein status (35)

82

(17% disagree)

33

(9% disagree)

RD along with AA profile

MD growth as indicator

Large discrepancy between RD and MD

4.9 +/- 1.3

Low agreement rating

DNPH should be used for home keto acid monitoring whenever clinically appropriate (36)

64

50

MD Don't do, stuff is hazardous

Harm noted

4.9 +/- 1.6

Low agreement

Ketone urinalysis strips should be used for home monitoring of ketones whenever clinically appropriate (37)

82

83

2 MDs easier than DNPH and meant for home use

Does "clinically appropriate" need to be clarified?

5.3 +/- 1.2

Plasma LEU should be routinely monitored as best marker of BCAA control in MSUD (38)

100

82

MD + 5 RDs in combination with other amino acid levels

MD LEU/ALA ratio probably superior

RD full panel allows ratios to be calculated

5.7 +/- 0.9

Laboratory (38-44) See TABLE #10, Delphi Round 1 - Lab Test Frequency for Medically Stable Individuals

Anthropometrics

All infants and children: height, weight, and head circumference should be assessed at each clinic visit (45a)

100

100

6.7 +/- 0.5

Adolescent: height, weight and BMI should be assessed at each visit (45b)

100

100

6.7 +/- 0.5

Adults: weight and BMI should be assessed at each visit (45c)

100

100

6.7 +/- 0.5

Developmental assessment / formal cognitive testing should be done on all children (46)

100

100

MD hard to get reimbursed, rely on school system

3 RD not available

Clarify general developmental assessment vs. formal cognitive testing

6.4 +/- 0.7

Dietary Intake Assessment

Dietary intake data should be assessed whenever blood sample taken for analysis (47)

82

100

MD better to have samples even without diet record

5.8 +/- 1.4

Dietary intake data should be analyzed whenever blood sample taken for analysis (48)

64

(36% disagree)

100

MD analyze q 3 mo

RD time consuming; now easier with metabolic pro

Discrepancy between RD and MD

5.0 +/- 1.5

Dietary intake data should be assessed when individual seen in clinic (49)

100

100

RD we ask for diet records

6.3 +/- 0.6

Dietary intake data should be analyzed when individual is seen in clinic (50)

73

(18% disagree)

100

RD not always necessary; time constraints impossible to do in clinic-report back later

Discrepancy between RD and MD

5.6 +/- 1.3

Docosohexanoeic acid (DHA) should be supplemented (56)

82

(9% disagree)

0

(33% disagree)

RD should be individual recommendation depending on age

RD yes based on recent evidence

Large discrepancy between MD and RD

4.4 +/- 1.1

Low agreement rating

Plasma BCAA Management Goals

If offending amino acids are >10% below normal values, more intact protein should be added to diet (57)

100

100

Should LEU, ILE, VAL be named?

6.0 +/- 0.6

VAL and ILE may be somewhat above the normal range (with LEU in desired treatment range) to avoid possible deficiencies (58a)

91

83

5.6 +/- 1.1

LEU concentrations up to 400 micromolar (5.2 mg/dl) with other BCAA in desired range (58b)

27

(55% disagree)

33

(50% disagree)

3.8 +/- 1.1

Strong disagreement

LEU concentrations up to 300 micromolar (4.0 mg/dl) with other BCAA in desired range (58c)

36

(36% disagree)

83

(0% disagree)

MD + 2 RD goal is 50-200 micromolar

RD 200-250

2 RD depends on age and clinical presentation

Large discrepancy between MD and RD

4.5 +/- 1.6

Low agreement rating

NEW DIAGNOSIS

Clinical Statement

(Item # on survey)

RD % Agreement

n=11

MD % Agreement n=6

Notable Comments

Discussion Points for Consideration

Agreement Rating (1-7)

Mean +/- SD

All individuals with MSUD should be assessed for thiamine responsiveness (51)

100

83

6.1 +/- 0.9

Appropriate dosage for testing thiamine responsiveness is 100 mg/d (52)

73

83

MD some need higher dose

5.4 +/- 0.9

The duration of trail of thiamine responsiveness should be at least one month unless clear response seen sooner (53)

73

67

MD may need longer

RD need to monitor diet for major changes that could confound interpretation

5.4 +/- 1.0

Thiamine responsiveness should be evaluated only after the patient and his/her BCAA levels have been stabilized (54)

46

(18% disagree)

67

(17% disagree)

3 RD not sure, don't have experience

Discrepancy between MD and RD

4.7 +/- 1.5

Low agreement

All newly diagnosed with MSUD should be given thiamine immediately regardless of BCAA levels or clinical stability (55)

64

50

4.9 +/- 1.6

Low agreement

CRITICAL ILLNESS

Clinical Statement

(Item # on survey)

RD % Agreement

n=11

MD % Agreement n=6

Notable Comments

Discussion Points for Consideration

Agreement Rating (1-7)

Mean +/- SD

If hemodialysis. peritoneal dialysis or exchange transfusion is utilized to reduce concentration of BCAA and their keto acids, it should be accompanied by aggressive nutritional support including energy, fluid and BCAA-free amino acid mixture (69)

100

100

MD should be done even if dialysis isn't required

More details needed regarding "aggressive" nutritional support

See comments for (70)

6.5 +/- 1.1

IV fluids with 10% dextrose should be provided at 1.5 to 2 times maintenance (70)

91

83

MD RD risk of brain edema is great, evaluate to determine if fluid restriction is needed

RD monitor NA and water balance, 2 X may be too much

RD may need higher % dextrose to reverse catabolism,

MD RD may need lipids to meet caloric needs

Harm pointed out

5.8 +/- 1.7

DIAGNOSIS OR CRITICAL ILLNESS

Comatose patients should be prescribed parenteral nutrition providing adequate BCAA-free amino acids, glucose and lipid (71)

100

100

MD need to use enteral AA mixture

MD try NG tube with infants if possible

MD We do not use BCAA-free solution, we use insulin and mannitol for brain edema

4 RD Use gut if possible

2 RD Provide BCAA (ILE, VAL) as soon as pt can tolerate to prevent catabolism

6.1 +/- 0.7

20% intralipids should be provided at 2 g/kg body weight per day (72)

81

100

MD RD use to maximize total calorie

RD Base on Kcal needs to provide approx 50% of calories

RD Depends on fluids and dextrose in PN

5.8 +/- 1.0

To allow sufficient glucose for anabolism, insulin should be required to prevent hyperglycemia (73)

81

83

MD insulin MAY be needed

2 RD individually asses, monitor blood glucose levels

MD Reason is to provide anabolic hormones to maximize protein accretion. Glucose levels not <150

5.5 +/- 1.5

Careful monitoring of hydration, electrolytes and neurological status is necessary to prevent cerebral edema (74)

100

100

MD mannitol and hypertonic saline are also required

6.5 +/- 0.5

Enteral feedings, total or partial should be introduced as soon as possible (75)

100

100

6.5 +/- 0.5

Each of the BCAA should be introduced at concentrations that provide the lower limit of recommended intake of the amino acid for age/weight (76)

91

83

MD agree IF this is after LEU levels have been decreased with treatment

2 RD depends on blood values, titrated on individual basis MD VAL and ILE need to be provided at higher levels

RD 20-120 mg/kg/d ILE, VAL

5.5 +/- 1.2

ILE and VAL supplementation should begin when plasma concentrations fall to the upper limit of the accepted treatment range (77)

91

67

MD +2 RD sooner, depending on other indicators of catabolism

5.4 +/- 1.3

LEU (from intact protein or complete amino acid mixture) should be introduced when plasma levels fall to the upper limit of the accepted treatment range (78)

91

83

MD RD sooner, individually assessed based on other indicators of catabolism

RD also based on time passed without natural protein (usually begin ¼ usual goal x 24 hr, then increase by 1/4s to full goal with time(usually every 24 hr) and based on blood levels and/or DNPH

5.5 +/- 1.1

SICK DAY (AT HOME) PROTOCOLS

Clinical Statement

(Item # on survey)

RD % Agreement

n=11

MD % Agreement n=6

Notable Comments

Discussion Points for Consideration

Agreement Rating (1-7)

Mean +/- SD

Should be individualized (79a)

100

100

6.6 +/- 0.5

Should include appropriate guidelines for monitoring keto acids and clinical status (79b)

100

100

6.4 +/- 0.6

Should include appropriate guideline for decreasing BCAA (79c)

100

100

6.5 +/- 0.5

Should include appropriate guidelines for maintaining fluid and energy intake (79d)

100

100

RD Should include guidelines for providing adequate calories without protein

Fluid and energy could be separate recommendations

6.5 +/- 0.5

Should include emergency contact information (79e)

100

100

6.6 +/- 0.5

WOMEN & PREGNANCY

Clinical Statement

(# on survey)

RD % Agreement

n=11

MD % Agreement n=6

Notable Comments

Discussion Points for Consideration

Agreement Rating (1-7)

Mean +/- SD

Note: Many respondents indicted they had no experience treating pregnant women with MSUD

82% of RDs

83% of MDs

Birth control medication may help minimize menstrual cycle-induced BCAA fluctuations (59)

46

67

4.8 +/- 1.2

Low agreement rating

Pregnancy

Guided by frequent laboratory monitoring, BCAA and protein intake should be increased throughout pregnancy to meet increased requirements (60)

100

100

High agreement for many items could be due to the general nature of the statements

6.4 +/- 0.5

Poor nutrient intake due to pregnancy-related nausea and vomiting should be treated aggressively to avoid endogenous protein catabolism (61)

100

100

Are recommendations needed for how to do this?

6.5 +/- 0.5

Carnitine should be supplemented if plasma free carnitine is below the established normal range (64)

82

(0% disagree)

33

(50% disagree)

MD whose normal range?

MD, RD have not seen it low in this pop.

MD not issue in MSUD

Large discrepancy between MD and RD

Can this issue be resolved with evidence?

4.9 +/- 1.9

Low agreement rating

Vitamin and mineral supplementation should be evaluated individually based on specific medical food prescribed, dietary adherence and the pregnant patient's laboratory assessment (65)

100

83

Is there any harm in giving to all (i.e., to treat like other pregnant women)?

6.4 +/- 0.8

Lab Tests (62, 63) See TABLE #10, Delphi Round 1 - Lab Test Frequency for Medically Stable Individuals

Delivery & Past Partum

Adequate energy should be provided during delivery and for 6 weeks postpartum to prevent catabolism (66)

100

100

MD will be catabolism of uterus no matter what

RD at least this long

6.2 +/- 0.8

Monitoring of metabolic labs should continue at least 6 weeks post partum (67)

100

83

6.1 +/- 0.8

After delivery, less protein (medical food and intact protein) should be prescribed than during pregnancy unless breastfeeding (68)

91

67

RD adjust based on amino acid levels

5.5 +/- 1.3

LIVER TRANSPLANT

Clinical Statement

(# on survey)

RD % Agreement

n=11

MD % Agreement n=6

Notable Comments

Discussion Points for Consideration

Agreement Rating (1-7)

Mean +/- SD

Note: Many respondents indicated no experience with MSUD liver transplantation

72%of RDs

67% of MDs

Individuals with MSUD who have had a liver transplant can safely consume a diet with unrestricted BCAA content (80)

63

50

2 MD + 3 RD note no experience

5.1 +/- 1.2

Moderate agreement

Can expect to have plasma BCAA and urinary keto acids in the normal range (81)

63

50

MD Alloisoleucine may be slightly elevated and may rise when sick but appears to have no clinical consequence

5.1 +/- 1.2

May need nutritional counseling to transition from a diet with medical food and very low protein foods to a "regular diet" with the DRI for protein and energy (82)

91

83

6.0 +/- 1.0

Should continue to have plasma amino acids analyses whenever liver function tests are ordered (83)

73

(18% neither agree or disagree)

33

(50% neither agree or disagree)

MD, RD once/year

RD Monthly for 6-12 months post transplant, always during serious illness (e.g., acute rejection, severe dehydration, etc.) and yearly after 12 months

Large discrepancy between MD and RD

4.9 +/- 1.2

Low agreement rating

Should be monitored for growth and nutritional status (84)

100

83

MD every 6 months

MD, RD reasonable based on other patients who have had a liver transplant

6.3 +/- 0.8

Completely disagree

Disagree

Somewhat disagree

Neither agree or disagree

Somewhat agree

Agree

Completely Agree

1

2

3

4

5

6

7

Recoded as Disagree

Recoded as Agree

Clinical Statement

(Item # on survey)

RD % Agreement

n=11

MD % Agreement n=6

Notable Comments

Discussion Points for Consideration

Agreement Rating

Mean +/- SD

BCAA levels when well

< 5 yrs, LEU upper limit 200 (15)

100

71.4

Normal AAA levels, allow more (250, 500)

Answers ranged from agree to disagree

5.68

> 5 yrs, LEU upper limit 300 (16)

75

57

Similar recommendations to < 5 years

4.84

Low agreement rating

All ages, LEU lower limit 75-100 (17)

83

85.7

Most comments state normal range, which may differ from lab to lab

One MD strongly disagrees - but no comment

5.0

All ages, ILE and VAL (18)

83

86

Usually higher than nl range

6.0

Acute illness

Aggressive increase anabolism, etc (19)

100

100

6.55

LEU elimination no more than 48 hr (20)

100

83

One complete disagree- may need up to 4 days

6.16

BCAA-free protein at 120-150% of usual (21)

83

66

150 may be excessive

5.27

Energy intake at 100-150% (22)

83

100

150 maybe excessive

5.77

Fluid intake at 100-150% (23)

92

67

May need to restrict, Need Na<135

Discrepancy between RD and MD

5.5

Reintroduction of LEU, at to (24)

92

67

Consider LEU levels, brain edema; would add back at 100%

5.72

Re intro of LEU when plasma LEU at upper level of tx range (25)

58

83

If plasma levels are falling rapidly, may add sooner

Discrepancy between RD and MD

5.0

Use of TPN if enteral not possible (26)

100

83

Because of lack of availability in first 24 hr, often must use only glucose and lipids

6.05

For TPN follow ASPEN guidelines(27)

66.7

33.3

May start TPN sooner (Aspen guidelines were not familiar to all)

Discrepancy between RD and MD

4.27

Low agreement rating

ILE and VAL supplementation (28)

92

83

6.33

Mild illness

Factors to consider for managing at home (29)

100

100

6.27

Reduce intact PRO by 50-100%, replace with BCAA-free (30)

100

100

Or more to get extra KCAL

6.0

LEU restriction for ≤ 48 hr (31)

100

100

With gradual reintroduction, some may need longer restriction

6.44

Adequate KCAL (32)

100

100

6.55

Continue or add VAL, ILE (33)

100

100

At 10-15mg/kg

6.16

Monitor physical, clinical signs of illness (34)

100

100

6.61

Monitor for urine a keto acids (35)

92

67

Not always available, use keto sticks for ketones

5.38

Maternal MSUD

Monitoring to ensure meeting extra needs (36)

100

100

Limited experience

6.55

Use of BCAA-free medical food (37)

92

100

6.27

Plasma BCAA in same target range as non-pregnant (38)

83

83

MD (1) may want a little higher; RD (1) may want a little lower

5.55

Treat aggressively nausea etc (39)

100

100

6.22

Illness guidelines same as non-pregnant (40)

56

83

More aggressive with closer monitoring

5.0

Vit and mineral supplementation per case (41)

100

100

6.47

IV glucose and lipids during L and D (42)

100

100

6.41

Restrict LEU post delivery (43)

64

100

Discrepancy between RD and MD

5.4

Close monitoring 6 weeks (44)

92

100

6.11

Nutrient requirements for breastfeeding MSUD woman (45)

73

66

5.29

Breast milk is appropriate LEU source for MSUD baby (46)

100

83

6.17

Using expressed breast milk with BCAA-free requires close monitoring (47)

100

100

6.05

Feeding at the breast (48)

92

67

Possible with close monitoring

Discrepancy between RD and MD

5.58

Liver transplant

In metabolic control prior (49)

82

83

Optimal, but those needing this form of Tx are those having the most problem with control

5.8

Minimize catabolism perioperatively (50)

91

83

5.9

Regular diet after transplant (51)

82

100

5.88

Transition counseling needed(52)

100

100

Experience with pt >10 who had difficulty including wgt loss

6.52

Monitor for growth, nutritional status…(53)

100

100

SOP for transplantation

6.64

Thiamin

Responders have partial enz activity (54)

54

100

Large discrepancy between RD and MD

5.41

100 mg adequate (55)

54

83

Perhaps even less

Discrepancy between RD and MD

5.11

4 weeksenough time for response (56)

64

100

Discrepancy between RD and MD

5.4

Need BCAA restriction with thiamin (57)

64

67

5.0

Monitoring: 0-24 mos

3-4 clinic visits (58)

100

83

More in year 1

6.0

Nutrition assessment with AAA (59)

100

83

6.17

Anthropometrics with each visit (60)

100

100

6.7

Transthyretin 2-3 x year (61)

92

67

Discrepancy between RD and MD

5.23

Iron indicies 1-2 x year (62)

100

83

6.05

Vit D, EFA, etc annually (63)

100

67

Discrepancy between RD and MD

5.88

Monitoring: 2-8 years

2-3 clinic visits (64)

100

83

6.17

Nutritional assessment with AAA (65)

100

83

6.23

Anthropometrics at visits (66)

100

100

6.76

Transthyretin 1-2 x year (67)

100

83

5.52

Iron 1-2 x year (68)

100

83

5.88

Vit D, EFA, etc annually (69)

100

83

5.94

Dexa scan at age 6 (70)

54.5

50

Data not good for 6 yo, if vit D and growth is good, no need for DEXA

4.76

Low agreement rating

Monitoring at home

Keto acids weekly up to 24 mos(71)

73

33

Concerns abt availability of DNPH for home use

Large discrepancy between RD and MD

4.88

Low agreement rating

Keto acids monthly in well 2-8 y (72)

55

50

Concerns abt availability of DPNH for home use. If available, use weekly.

Need for monitoring depends of severity of mutation

4.7

Low agreement rating

Keto sticks show ketones/catabolism (73)

100

100

6.17

DNPH is more sensitive to a-ketoacids (74)

82

67

5.88

AAA 1-2 x mos up to 24 mos (75)

82

67

5.52

AAA monthly 2-8 yr old (76)

91

83

6.23

Daily observation of signs and symptoms (77)

100

83

6.17

Home monitoring with diet change and possible impending illness for all ages (78)

100

100

6.4

Completely disagree

Disagree

Somewhat disagree

Neither agree or disagree

Somewhat agree

Agree

Completely Agree

1

2

3

4

5

6

7

Recoded as Disagree

Recoded as Agree

Yellow

Green

Blue

White

Test/Frequency

Infants

Children 1-10 yr

Adults, Children >10 yr

Comments

RD %

MD %

All %

RD %

MD %

All %

RD %

MD %

All %

Complete blood count with differential (whole blood)

Monthly

18

12

3 months

9

6

9

6

6 months

36

33

35

36

24

36

24

Yearly

36

67

47

56

100

71

64

83

71

Never

0

0

0

0

0

0

17

6

Comprehensive metabolic panel

Monthly

36

24

9

6

3 months

9

6

9

6

6 months

18

33

24

36

17

29

46

17

35

Yearly

36

50

41

36

50

41

46

33

41

Never

0

17

6

9

33

18

9

50

24

Amino Acids (plasma)

Weekly

27

17

24

Biweekly

27

33

29

27

33

29

18

17

18

Monthly

27

33

29

27

0

18

27

0

18

3 months

0

0

0

9

33

18

9

0

6

6 months

18

0

12

36

0

24

38

67

47

Yearly

0

0

0

0

17

6

9

0

6

Never

0

17

6

0

17

6

0

17

6

Carnitine, free, esterified and total (plasma)

Monthly

18

12

3 months

9

17

12

17

6

6 months

9

17

0

18

0

12

9

17

12

Yearly

0

0

12

27

17

24

27

17

24

Never

55

67

60

54

67

59

64

67

65

Transthyretin (plasma)

Biweekly

9

6

Monthly

9

6

9

6

9

6

3 months

18

12

0

0

0

6 months

27

33

29

36

17

29

27

17

24

Yearly

36

50

41

45

33

41

46

17

35

Never

0

17

6

9

50

24

18

67

35

Ferritin (plasma)

Monthly

9

6

3 months

18

12

0

6 months

36

17

24

36

29

9

6

Yearly

27

67

47

45

50

41

73

50

65

Never

18

17

18

18

59

24

18

50

29

Test/Frequency

Infants

Children 1-10 yr

Adults, Children >10 yr

Comments

RD %

MD %

All %

RD %

MD %

All %

RD %

MD %

All %

Essential fatty acid profile (plasma)

Write in:
Test EFA if on low fat formula

6 months

Yearly

27

33

29

73

33

59

55

33

47

Never

73

67

71

27

67

41

46

67

53

Essential fatty acid profile (erythrocyte)

Write in:
Adults test every 5 years

6 months

9

6

Yearly

46

17

35

64

17

47

46

17

35

Never

46

83

59

36

83

53

54

83

65

Folate (erythrocyte)

6 months

9

6

9

6

Yearly

55

17

41

64

17

47

73

17

53

Never

36

83

53

27

83

47

27

83

47

Vitamin B12 (serum)

6 months

18

12

9

6

Yearly

36

50

41

73

50

65

82

50

71

Never

46

50

47

18

50

28

18

50

29

Vitamin D 25-OH (plasma)

3 months

9

6

6 months

9

17

12

46

29

18

12

Yearly

64

67

65

46

100

65

73

83

76

Never

18

17

18

9

0

6

9

17

12

Trace minerals (selenium, zinc) (serum)

3 months

9

6

6 months

18

12

9

6

Yearly

36

17

29

82

16

59

82

17

59

Never

36

83

53

9

83

35

18

83

41

Amylase (serum)

Amylase write in:
Only if ill

3 months

17

6

6 months

9

0

6

Yearly

18

0

12

18

17

18

9

17

12

Never

73

83

77

82

83

82

91

83

88

Lipase (serum)

Lipase write in:
Only if ill

3 months

17

6

6 months

18

0

12

9

6

Yearly

9

0

6

18

17

18

27

17

24

Never

73

83

77

73

83

77

73

83

77

Lipid profile (total chol, HDL, LDL, triglycerides) (serum)

Lipid profile write in:
Children every 5 years
Adults every 5 years

3 months

6 months

9

6

Yearly

36

17

29

46

33

41

73

17

53

Never

55

83

65

55

66

59

27

83

47

Organic acids (urine)

Monthly

18

0

12

18

12

3 months

9

17

12

0

0

6 months

9

17

12

9

17

12

8

6

Yearly

27

0

18

27

17

24

36

33

35

Never

36

67

47

46

67

53

55

67

59

DEXA scan beginning at age 6

Write in:
DEXA every 3-5 yr, 5 yr

Yearly

NA

NA

NA

64

67

65

91

33

71

Never

36

33

35

9

67

29

Do not do:

No consensus:

Amylase

Folate

Lipase

Trace minerals

Carnitine

Lipid profile in children and adults

Essential fatty acid

Amino acids (need to separate out BCAA

Organic acid (urine)

Test

Infants

Children

Adults & Children >10 yr

CBC

6 mo or yearly

Yearly

Yearly

Comprehensive Metabolic Panel

6 mo or yearly

6 mo or yearly

Transthyretin

6 mo or yearly

6 mo or yearly

Ferritin

6 mo or yearly

6 mo or yearly

Vitamin B12

?

Yearly

Vitamin D 25 OH

Yearly

Yearly

DEXA

NA

Yearly