maple syrup urine disease (msud)
TRANSCRIPT
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
1/28
Maple Syrup Urine DiseaseDr. Mohammed Al f ri MD
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=FwBB31MeoCKk4M&tbnid=kLSGHz4WDnQnyM:&ved=0CAUQjRw&url=http://www.92citifm.ca/2013/05/27/canadian-money-smells-like-syrup/&ei=-y3ZUu37Csin0AWirIGQDQ&bvm=bv.59568121,d.d2k&psig=AFQjCNFOBPBm9LhRzk9EKeUkZH1jFm-MAw&ust=1390051185371476 -
8/13/2019 Maple Syrup Urine Disease (MSUD)
2/28
1. What is MSUD?
2. Epidemiology
3. Pathophysiology
4. Types of MSUD
5. Presentations
6. Diagnosis
7. Management Of Crisis
Outline
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
3/28
maple syrup found in body fluids especially urine autosomal Recessive
varying forms
results in mental retardation/death
Epidemiology1:185,000 live births.
Mennonites in Pennsylvania (1:200).
MSUD
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
4/28
Prof. John Menkes (1928-2008)Neurology and Pediatrics at the University of California School of Medicine
first known case: 954
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
5/28
Branched Chain Amino Acids
Pathophysiology
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
6/28
Catabolism
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=XbP-GO859pO7AM&tbnid=xndUaYRGvAOrWM:&ved=0CAUQjRw&url=http://mural.uv.es/ramah/Metabolismo.html&ei=pv_YUrKxJ8eb0wX69YGIAg&bvm=bv.59568121,d.d2k&psig=AFQjCNEadxTtFfNSGLCvqJw-MiV_TngGhQ&ust=1390039310855297 -
8/13/2019 Maple Syrup Urine Disease (MSUD)
7/28
dehydrogenase is thiamine dependent enzyme
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
8/28
cause maple syrup smell
most toxic
Primary cause of neurotoxicity of MSUD.
High leucine appear to impair regulationof cell volume, by decreasing serum Na+
andincreased intracellular water, leading
to cerebral edema.
Significant?
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
9/28
1. Lethargy, irritability
2. Poor feeding
3. Nausea, vomiting4. Hypotonia, hypertonia, dystonia
5. Ataxia
6. Seizures
7. Coma
8. Maple syrup odor (urine, ear wax)
Acute Presentation
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
10/28
1. Classical: little or no enzyme activity
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
11/28
Breastfeeding may delay onset of symptoms to the second week.
Time Symptom/Sign
12-24 hours Maple syrup odor
2-3 days Irritability, poor feeding, Ketonuria
4-5 days Encephalopathy, apnea, atypical movements
7-10 days Coma and respiratory failure
Classic:
is the most common form
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
12/28
Intermediate:
usually diagnosed between ages 5 months and 7years.
Intermittent:
asymptomaticbut at risk for metabolic crises during acute
illness, usually infection.
Thiamine-responsive: do not respond to thiamine supplementation alone, and
dietary restriction of branched-chain amino acids is needed to
achieve metabolic control.
E3-deficient:
typically present in the newborn period
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
13/28
PRIMARY LEVEL TESTS:
Blood Glucose & Electrolytes, Blood Gas
Urine Ketones: Very reliable test in newborn to suggest presence of IEM
Plasma Ammonia
SECONDARY LEVEL TESTS:
Blood Tandem Mass Spectrometer (TMS)
Highly reliable test, can diagnose up to 30 different IEM on a dried
blood spot specimen.
MSUD profile
DIAGNOSIS
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
14/28
MSUD profile: to measure plasma amino acids (fast 4hr
before test)
isoleucine & valine levels may drop rapidly will keep the leucine levelfrom dropping.
Add isoleucine& valine at 100-150 mg/kg/day to achieve the goal
levels.
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
15/28
Dietary therapy (MSUD formula):
i. goal is to achieve normal plasma concentrations of BCAA, especially
leucine.
ii. Sufficient quantities of BCAA are provided to support normal growth
and intellectual development.
iii. throughout life.
MSUD profile every 1-2 weeks for the first 6-12 months of age.
thiamine (50 to 300 mg/kg) should be given for four weeks to test forthiamine-responsiveness.
Newly diagnosed
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
16/28
MSUD formula
Maxijul Ketonex
BCAA and thiamine
Nan1
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=dLagHF7Sw1FIKM&tbnid=0akiwFu9y3JipM:&ved=0CAUQjRw&url=http://www.supermama.lt/forumas/lofiversion/index.php/t35744-100.html&ei=jyfZUo27HMKL0AWshoDoDA&bvm=bv.59568121,d.d2k&psig=AFQjCNFeEAd-hwABqqejvJkoAKqfj1_tjw&ust=1390049531796971https://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=_PRFGxvzGFa7SM&tbnid=PO_ZtteMLZUeQM:&ved=0CAUQjRw&url=https://www.halfpriceperfumes.co.uk/en/all-pharmacy/39916-maxijul-super-soluble-dietary-supplement-200g-5016533634815.html&ei=aSXZUtn2M_CX0QWCxICICA&bvm=bv.59568121,d.d2k&psig=AFQjCNFv6CDZq7sPsU-PiaaRWNswxOZHdA&ust=1390048959466482 -
8/13/2019 Maple Syrup Urine Disease (MSUD)
17/28
Do not wait for the confirmation of diagnosis, as any delay will
lead to poor neurological outcome.
collect all necessary tests, must be done before starting any
treatment, as the treatment will alter the biochemical
parameters.
Management Of Crisis
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
18/28
1. Protein intake protein should be restricted at the beginning to ONLY the
medical formula without adding natural protein (Milk etc.) synthetic protein is started very quickly and is used as part
of the emergency management.
2. Hydration:should be kept NPO until mental status is improved.
1.5 times maintenance rate
D10% + 0.9 NS +10 mmol kCl
strict input|output
if balance more than150 to give lasix
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
19/28
3. Caloric Supplementation:
intralipid
1.5g/kg/day
given as IV
pancreatic enzymes (amylase & lipase) should be checked
before starting it
http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=xbyUOAxy356DaM&tbnid=lzJ1qYsQc2gb4M:&ved=0CAUQjRw&url=http://www.medline.com/product/INTRALIPID-20-IV-Fat-Emulsion-by-Baxter-Healthcare/Fat-Emulsion/Z05-PF34065&ei=k1LVUr-0Gqmq0QXIg4EI&bvm=bv.59378465,d.ZGU&psig=AFQjCNEhaxZeQbBMSR3tLhn2LSoJEvC8mw&ust=1389798337553639http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=_UKxvFpOG3MMwM&tbnid=3GP_0YspePnRYM:&ved=0CAUQjRw&url=http://www.onegoodembryo.com/recurrent-miscarriage/treatments/immunological-treatments/intralipid/&ei=T1LVUsnjDKmb0wX_kYGQCg&bvm=bv.59378465,d.ZGU&psig=AFQjCNEhaxZeQbBMSR3tLhn2LSoJEvC8mw&ust=1389798337553639 -
8/13/2019 Maple Syrup Urine Disease (MSUD)
20/28
4. Correct Metabolic acidosis:
should slowly correct with rehydration and high caloric intake.
Aims are:
serum bicarbonate level over 24 meq/Labsence of ketones in urine.
formula IV sodium Bicarbonate:
0.6 X Weight X Bicarbonate deficit = mmol
bicarbonate required
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
21/28
5. Precipitating factors:Infection: Antibiotics.
Surgery: D10 prior to and after surgery until oral fluids are tolerated.
avoiding prolonged fasting to the extent possible.
addressing pain issues.
providing adequate calories to promote fast healing.
6. Hemodialysis indications:
intractable metabolic acidosis.severe electrolyte disturbances
and/or if patient is comatose.
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
22/28
Management Of Crisis:
1. Protein intake
2. Hydration
3. Caloric Supplementation
4. Correct Metabolic acidosis5. Precipitating factors
6. Hemodialysis
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
23/28
7. Cerebral Oedema
inform senior staff immediately.
Exclude hypoglycemia Elevate the head side of the bed
Give Mannitol 0.5 g/kg stat (= 2.5 ml/kg Mannitol 20% over
15 minutes). This needs to be given within 10 minutes.
Reduce rate of fluids to half immediately and recalculate to
2/3 maintenance and replace deficit over 72 rather than 24
hours.
need to be moved to ICU.
Arrange for the child to be intubated and if necessary
hyperventilated to reduce blood pCO2. Exclude other diagnosis by CT Scan but only after ICU
stabilization
Repeated doses of Mannitol (above dose every 6 hours)
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
24/28
Clinical parametersMental status
Hydration status/fluid balance/oral intake
Biochemical parameters:-Urine for ketones with every void
-MSUD profile (once daily)
-amylase & lipase once daily
-Glucose, CBC, U&E, blood gases, NH4as indicated
Monitoring
C iti th f MSUD
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
25/28
Carnitine therapy for MSUD
Liver transplantation
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
26/28
Liver transplantation
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
27/28
-
8/13/2019 Maple Syrup Urine Disease (MSUD)
28/28
1. New England Consortium of Metabolic Programs[newenglandconsortium.org].
2. uptodate.com
3. medscape.com
4. SQUH protocol 2008
References:
Special thanks go to
Dr. Fathiya Al Murshedi, MD, M.Sc, FRCPC, FCCMG, CIPClinical and Biochemical Geneticist. SQUH