Metabolic Disorder Maple syrup urine disease by Dr Asad Abbasi. in this presentation you will learn about the clinical presentation of maple syrup urine disease and its types and management.

1. Metabolic Disorder
Dr Asad Abbasi

2. Case scenario
 A 2 week old male infant born at term after an uneventful pregnancy via
normal vaginal delivery. Baby presented with slight irritability and reluctant
to feed in 2nd week of life. Newborn’s screening were abnormal showing
elevated BCCA , confirmatory testing done with the plasma amino acid
levels collected at 8th day of life revealing elevated levels of leucine. Patient
was thereafter admitted where he exhibited irritability, high pitched cry and
hyper tonicity.
 O/E he was found normothermic, vitally stable and lab tests revealed
metabolic acidosis (HCO3=14), urinary ketones > 80 mg/dl , mild increased
ammonia level (NH3= 83micromol/L) . MRI shows restricted diffusion
involving the corticospinal tracts, globus palladi, midbrain and cerebellar
white matter.extensive bilateral T2 fluid attenuated inversion recovery white
matter hyperintensity was also noted.

3. Diagnosis= MAPLE SYRUP URINE
DISEASE

4. INTRODUCTION
 Maple syrup urine disease is a rare genetic disorder which
is characterized by deficiency of mitochondrial enzyme
BCKDHA which uses thiamine pyrophosphate as a co-
enzyme, this enzyme has 4 subunits E1α, E1β, E2 and E3
causing decarboxylation of leucine, isoleucine and valine.
Deficiency of any of the following causes MSUD.


5. Clinically these can be referred
as
 Type 1A for E1 α which is mild to severe type.
 Type 1B for E1 β
 Type 2 for E2
 Type 3 for E3
Risk factors
Mostly genetic, effects both male and female equally, occur about 1 in
185000.
If both parents are carrier than child has
25% chances of receiving 2 mutated genes and having MSUD.
50% chance for receiving only 1 defective gene and leads to become a
carrier.
25% chances of receiving 1 normal gene from each parent

6. Clinical Features
Mostly classic MSUD type shows severe symptoms
 Lethargy
 Poor appetite
 Weight loss
 Weak sucking ability
 Irritability
 Maple syrup odor in urine & sweat
 Irregular sleep pattern
 Alternating episodes of hypertonia & hypotonia
 High pitch cry
 Neurological deficiencies

7. Classification
 Based on clinical findings & response to thiamine
1. Classic Maple Syrup Urine Disease
Severe & common type, people have about 2% or less of normal enzyme
activity.
Symptoms; poor feeding, vomiting, hypertonicity, flaccidity, cerebal edema,
hypoglycemia, convulsions and death.
Diagnosis:
>particular odor of maple syrup in urine & sweat.
>Amino Acid analysis= increase plasma levels of leucine, isoleucine & valine.
Decreased level of alanine.
>Neuroimaging= shows cerebral edema which is prominent in cerebellum,
dorsal brain stem, internal capsule & cerebral peduncle.
Rx: removal of BCAAs & their metabolites from tissue & body fluids
Sufficient calories & nutrients
Low diet of BCAAS > hemodialysis

8. 2. Intermediate (mild) Maple syrup urine disease: Insidious in onset. Mild
type. People have high level of enzyme activity about 3 to 8%.
Symptoms: similar as in classic type with mild to moderate intellectual disability
with or without seizures.
Dx: same as classic type.
RX: same as of classic type along with thiamine therapy.

9. 3. Intermittent Maple syrup urine disease:
Milder form & 8 to 15% of normal activity.
Symptoms appear between 1 to 2 years.
Symptoms: Vomiting, odor in maple syrup in urine, ataxia, lethargy & coma
during stress conditions.
Dx & Rx: similar
4. Thiamine Responsive Maple syrup urine disease:
Mild to intermedia form.
Symptoms; occur after infancy but are similar one.
Dx & Rx: same , thiamine @ 10mg/ 24hrs or 100mg/24hours for at least 3
weeks is given.

10. 5. Maple syrup disease caused by def: of E3 subunit:
It is referred as MSUD type 3.
Rare type.
Sign & symptoms are similar to intermediate type.
Neurological involvement.
No proper treatment is available, although low diet BCAAs, thiamine doses are
given.
Lab findings include persistent lactic acidosis with high level of alanine &
plasma pyruvate. Excretion of lactate, pyruvate & alpha-ketoglutarate in
urine.

11.  Diagnosis: Family history
Genetic studies
Urine amino acid test
Plasma amino acid test
Treatment:
Protein limited diet
Tracking of BCAAs levels
Thiamine supplements
Hemodialysis
Liver transplant

12.  Complications:
Neonates= Metabolic crisis
(suddden increase of BCAAs) leading to physical & neurological changes
indicated by
1/ extreme fatigue & lethargy
2/ loss of alertness
3/vomiting
4/irritability
5/seizures & cerebral edema
6/ blindness
7/intellectual disability
8/ death

13.  Long term outlook of MSUD
 Child can lead to active , normal live with regular monitoring, diet restriction
& prevention of complications by early diagnosis and treatment.

14. Thank you