[MIM 248 600615 135]

(Maple syrup disease, maple syrup urine disease, MSUD, branched-chain ketoaciduria)

Prevalence: 1/225,000 births but higher in populations where inbreeding is important: for example, 1/150 in communities Mennonites in North America. Autosomal recessive transmission of a mutation of the DBT gene on 1p21.2 (type II), BCKDHB gene on 6q14.1 (type Ib) or BCKDHA gene on 19q13.2 (type Ia). A mutation in the gene coding for a third element (E3) of the enzymatic complex (DLD on 7q35) is sometimes classified as maple syrup urine disease type III or deficient E3 (MIM 246 900). 

Disturbance of the metabolism of branched-chain amino acids (leucine, isoleucine, valine) at the level of a mitochondrial multienzyme complex  (α-cetodecarboxylases which includes 3 subunits: E1 alpha, beta E1 and E2). The result is the accumulation of these amino acids and their ketonic acids. Disease normally detected by neonatal screening. Enzyme activity varies according to the tissue: 60 % in the muscles, 10 to 20 % in the brain, 10 % in the kidneys and 10 % in the liver.

Symptoms vary with the importance of enzymatic deficiency:

-         neonatal acute form (< 1% enzymatic activity): the first days of life, difficulties in feeding, vomiting, lethargy, myoclonus, convulsions, cerebral edema;

-         crude or intermediate form  (3-8% enzymatic activity): according to the % of residual enzyme activity, intellectual deficit and motor retardation;

-         intermittent form (8-15% enzymatic activity): repeated ketoacidotic coma crisis, at all ages. The biological signs of leucinosis are present during these crises.

-         form deficient E3: very severe phenotype.

-         (very rare) thiamine-responsive form where the level of leucine normalizes following the administration of thiamine.

Diet limiting protein intake to about 2 g/kg/d. Despite the regime that makes the asymptomatic patient, the disease may be manifested by acute episodes of metabolic acidosis with ketosis (sometimes hypoglycemia, hyperlactacidemia and hyperammonemia) fever or ingestion of protein. Prompt treatment of these crises is necessary to avoid neurological sequelae (acute cerebral edema) or death: infusion of glucose 10% and bicarbonates, restriction of protein intake, sometimes dialysis peritoneal. 

Some cases of liver transplantation have been reported, some in which the native liver was used for a transplant 'in domino' for another child because a stable enzyme level of 10% of extrahepatic origin (muscle, brain, heart) is quite sufficient to maintain homeostasis of these amino acids.

In case of a thiamine-dependent form, to administer 5-20 mg/kg of thiamine.

Anesthetic implications

special diet. Avoid any hypoglycemia: limiting the duration of preoperative fasting (administer a glucose solution as soon as the fasting period starts). Empty the stomach to prevent a protein intake by the digestive route in case of surgery where blood may be swallowed (ENT surgery, stomatology).

References : 

 -        Kahraman S, Ercan M, Akkus O, Ercelen O, Erdem K, Coskun T. 
Anaesthetic management in maple syrup urine disease. 
Anaesthesia 1996; 51:575-8.

-         Delaney A, Gal TJ. 
Hazards of anesthesia in maple-syrup urine disease. 
Anesthesiology 1976; 44: 83-6

-         Fuentes-Garcia D, Falcon-Arana L.
Perioperative management of a patient with maple syrup urine disease. 
Br J Anaesth 2009; 102: 144-5

-         Karahan MA, Sert H, Havlioglu I, Yuce HH. 
The anaesthetic management of a patient with maple syrup urine disease. 
Turk J Anaesth Reanim 2014; 42: 355-7.

-         Orphananesthesia.eu : Maple syrup disease

-        Mohan N, Karkra S, Rastogi A, Vohra V, Soin AS.
Living donor liver transplantationin maple syrup urine disease- Case series dans worlds youngest domino liver donor and recipient.
Pediatr Transplantation 2016; 20:395-400

Updated: February 2018