Maple Syrup Urine Disease (MSUD)

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Maple Syrup Urine DiseaseDr. Mohammed Al f ri MD
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1. What is MSUD?

2. Epidemiology

3. Pathophysiology

4. Types of MSUD

5. Presentations

6. Diagnosis

7. Management Of Crisis

Outline


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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


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Prof. John Menkes (1928-2008)Neurology and Pediatrics at the University of California School of Medicine

first known case: 954


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Branched Chain Amino Acids

Pathophysiology


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Catabolism
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dehydrogenase is thiamine dependent enzyme


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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?


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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


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1. Classical: little or no enzyme activity


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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


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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


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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


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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.


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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


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MSUD formula

Maxijul Ketonex

BCAA and thiamine

Nan1
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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


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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


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3. Caloric Supplementation:

intralipid

1.5g/kg/day

given as IV

pancreatic enzymes (amylase & lipase) should be checked

before starting it
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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


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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.


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Management Of Crisis:

1. Protein intake

2. Hydration

3. Caloric Supplementation

4. Correct Metabolic acidosis5. Precipitating factors

6. Hemodialysis


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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)


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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


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Carnitine therapy for MSUD

Liver transplantation


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Liver transplantation


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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

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Maple Syrup Urine Disease (MSUD)

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