Maple Syrup Urine Disease (MSUD)

A typical case of MSUD

PRESENTATION: 

8 day old Term, AGA male baby, Parents had a non

 consanguinous marriage with no H/o unexplained death in family.
Baby presented with poor feeding, lethargy, persistent seizures, failure to thrive.
O/E baby was drowsy with tonic posturing of all limbs.


BIOCHEMICAL AND OTHER EVALUATION: 
Serum electrolytes, Calcium , Magnesium were normal.
Urine ketones positive
EEG Showed focal sharp wave activity over Left fronto-temporal areas.

CT revealed gross diffuse cerebral edema with involvement of the posterior fossa also

MRI FLAIR : Hyperintensities involving deep cerebellar regions with involvement of brainstem, thalami and corticospinal tracts.

MRI Diffusion : Restricted diffusion involving deep cerebellar regions with involvement of brainstem, thalami and corticospinal tracts.


1 week later Tandem Mass Spectroscopy revealed increased levels of branched chain amino acids (Valine, Leucineand Isoleucine) –confirming the diagnosis of MSUD

DISCUSSION:

Etiology: Autosomal recessive, Branched chain organic aciduria resulting from abnormalities of enzyme catabolism of branched chain amino acids. It leads to accumulation of BCAA and metabolites (neurotoxic). Accumulation of leucine in particular causes neurological symptoms. Increased Plasma isoleucine is associated with maple syrup odour.

Epidemiology : 1:850,000 general population, but can be as frequent as 1:170 in population isolates

Presentation:

Normal at birth , Presents after disease free interval, usually within the 4-7 days of life with poor feeding, vomiting, poor weight gain, increasing lethargy. Patients in crisis often smell like maple syrup

Maple syrup odor may be difficult to identify in first days of life unless urine soaked diaper is allowed to dry

Tandem mass spectrometry shortens diagnosis time

Mimic of sepsis: Acute encephalopathy, vomiting, seizures, neurological distress, lethargy, coma,

Plasma detection of alloisoleucine is diagnostic for MSUD

Typical EEG : "Comb-like-rhythms“

IMAGING FEATURES :
Classic appearing MSUD edema involving : Cerebellarwhite matter, brain stem, globuspallidus, thalamus, cerebral peduncles, corticospinaltracts (to cortex)
CT Findings
NECT : Diffuse edema NOT sparing brainstem and cerebellum
MR Findings
TlWI: decreased Signal intensity, margins may be sharp
T2WI : Generalized and MSUD edema
FLAIR: Generalized and MSUD edema
DWI : Marked restriction and decreased ADC (MSUD edema = intramyelinic)
MRS: Broad peak at chemical shift of 0.9 ppm
Ultrasonographic Findings
Increased Echogenicityof globuspallidi, periventricularwhite matter, and areas typically involved by MSUD edema


Treatment:
Acute "metabolic rescue" to reverse cerebral edema. May require hemodialysis during acute crisis to limit neurotoxicity/damage
Metabolically appropriate diet (protein-modified)minimizes severity
Prevent deficiencies of essential amino acids
Dietary therapy must be lifelong
Orthotopic liver transplantation increases availability of BCKD (rarely used)
Gene therapy experimental