Download Maple Syrup Urine Disease – Clinical Management Pathway

Maple Syrup Urine Disease – Clinical Management Pathway
Positive Screen
Clinical team notified-report before 12 noon
Contact Family
Instruct to go to local hospital if not inpatient
Liaise with Local Hospital
(may already be inpatient)
Ix-Blood gas, U&E, LFTs, fbc, cultures, ketones dipstick
Mx-stop feeds, IV 10% dextrose /0.45% saline + added potassium
Ambulance Transfer
If GCS < 8-intubate and ventilate and organise PICU retrieval
Admit to Specialist IMD Centre
Same day
Diagnostic Tests + Consent to study
Urgent Amino acids
Organic acids
MSUD
Manage as
MSUD
Yes
Alloisoleucine
Positive?
No
Original NBS Card
Alloisoleucine
Positive?
Yes
? Intermittent MSUD
Send fibroblasts for enzymology
Manage as MSUD until result known
Maple Syrup Urine Disease
nd
Clinical Management Pathway V1.2 Dated 2 Oct 2012
Approved by Michael Champion
No
Presumptive
False positive
Investigate & treat
Exclude liver
disease including
galactosaemia
MSUD Management of Sick Neonate
Stop breast feeding (continue expressing) and or standard formula feeds (temporarily)
Consider dialysis/haemofiltration dependent on clinical condition and leucine level
Promote anabolism
Calories 120-140kcals/kg/day
BCAA free protein
MSUD Anamix infant oral or NG as tolerated, or MSUD Aid III if fluid
restricted, to provide at least 3g/kg/day protein equivalent
Give Isoleucine & Valine supplements, 100-200mg each, to maintain target levels (see below)
If feeds poorly tolerated  IV 10% dextrose + added electrolytes (+/- insulin if hyperglycaemic)
+ NG BCAA free formula/supplement (as tolerated)
+ IV Intralipid 2g/kg/day
Use BCAA-free TPN if not absorbing and available
Patients with decompensated MSUD are at risk of cerebral oedema
Avoid hyponatraemia which may exacerbate this risk.
Goals of Treatment
Leucine
decrease >750mol/L each 24 hours until within target range
Isoleucine & Valine
maintain in target range
(avoid low levels which are rate limiting for protein synthesis)
negative
Ketones
Leucine
200-400
Leucine
(mol/L)
> 800
Isoleucine
200-400
400-800
reintroduce 2 exchanges (100mg)
Valine
200-400
200-400
reintroduce 4 exchanges (200mg)
Target Levels (mol/L)
Monitoring
Fontanelle and head circumference
BCAAs
U&E
Ketones (urine dip)
bd
daily
bd
bd
Maple Syrup Urine Disease
nd
Clinical Management Pathway V1.2 Dated 2 Oct 2012
Approved by Michael Champion
Guide to re-introducing protein
(leucine exchanges)
no natural protein
MSUD Management of Asymptomatic Neonate
Oral/NG feeds given as BCAA free formula (as tolerated) +/- natural protein
as per guide below (given as EBM or formula feed)
Promote Anabolism
Calories 100-120kcals/kg/day
BCAA free protein
MSUD Anamix infant oral or NG as tolerated to provide at least 3g/kg/day
protein equivalent and 150-180mL/kg/day
Isoleucine & Valine Supplement to maintain target levels as needed
Leucine
Given as natural protein.
1 exchange = 50mg leucine
1 exchange = 45mL EBM
1 exchange = 35mL formula feed
Goals of Treatment
Target Levels (mol/L)
Leucine
200-400
Isoleucine
200-400
Valine
200-400
Ketones
Leucine
(mol/l)
> 800
Guide to re-introducing protein
(leucine exchanges)
no natural protein
400-800
reintroduce 2 exchanges (100mg)
200-400
reintroduce 4 exchanges (200mg)
negative
Monitoring
Fontanelle and head circumference
BCAAs
Ketones
daily until stable
daily until stable
daily until stable
Maple Syrup Urine Disease
nd
Clinical Management Pathway V1.2 Dated 2 Oct 2012
Approved by Michael Champion
MSUD Formulas & Supplements
MSUD Anamix Infant (SHS)
15% dilution (1 level 5g scoop + 30ml water)
Per 100g
Energy (Kcal)
457
Protein (g)
13.1
CHO (g)
49.5
Fat (g)
23
Per 100ml
69
2
7.5
3.5
1 yellow scoop = 5g powder
1 large blue scoop = 26g powder
MSUD AID III (SHS)
5% dilution (1 level 5g scoop + 100ml water)
Per 100g
Energy (Kcal)
334
Protein (g)
79
CHO (g)
4.5
Fat (g)
nil
Per 100ml
16.7
3.95
0.23
nil
1 yellow scoop =
5.7g powder
1 large blue scoop = 32g powder
Valine Sachet
Energy (Kcal)
Valine (mg)
CHO (g)
Per 100g
384
1250
96
Per 4g sachet
15
50
3.8
Per 100g
384
1250
96
Per 4g sachet
15
50
3.8
Isoleucine Sachet
Energy (Kcal)
Isoleucine (mg)
CHO (g)
IV Dextrose
% dextrose
10%
12.5%
15%
20%
Energy (Kcal)/ml
0.34
0.43
0.51
0.68
Energy (Kcal)/100ml
34
43
51
68
Intralipid
10% solution (1.1Kcal/ml)
20% solution (2.0Kcal/ml)
0.8ml/kg/day
0.4ml/kg/day
Maple Syrup Urine Disease
nd
Clinical Management Pathway V1.2 Dated 2 Oct 2012
Approved by Michael Champion
=
=
2g/kg/day
2g/kg/day
Follow Up 1st Year
Home Monitoring



BCAAs weekly
Urine ketones as required during intercurrent illness
Weekly or fortnightly weighing until 1st outpatient appointment
Outpatients




1st follow up 4-6 weeks
Then 3-4 monthly for clinical and dietetic review/education
Weight/length
Amino acids
Outcome Measures








Age at diagnosis
Time to leucine <400mcmol/L from notification
Admissions first year
Outpatient attendance (% of expected)
Median leucine level for 1st year
Frequency of blood tests 1st year (% of expected)
Growth centiles end of year 1
Developmental Assessment at 1 year
Maple Syrup Urine Disease
nd
Clinical Management Pathway V1.2 Dated 2 Oct 2012
Approved by Michael Champion