[MIM  251 000]

Rare (1/25,000-1/50,000). Autosomal recessive metabolic disease caused by an abnormality of the conversion of methylmalonyl-CoA to succinyl-CoA following a deficiency in methylmalonyl-CoA mutase enzyme  (MUT gene on 6p21.1) (50-70% of patients) or the adenosylcobalamine coenzyme derived from vitamin B12 (approximately 30% of patients). These enzymes are involved in the metabolism of leucine, isoleucine and valine. The accumulation of methylmalonic acid causes secondary propionic acidemia and carnitine deficiency. 

Mutase deficiency can be:

-         full (mut0): neonatal severe form; this form is said to be resistant to vitamin B12

-         partial (mut-): later presentation, after a month of life, and even later for the shape due to adenosylcobalamine deficiency

The form due to adenosylcobalamine deficiency is said to be sensitive to vitamin B12.

Neonatal clinical presentation: sepsis-like, lethargy, coma, hypotonia, vomiting, convulsions, sometimes hepatomegaly. 

Later clinical presentation: hypotonia, mental retardation, dystonia, epilepsy, episodes of ketoacidosis, acute pancreatitis, anorexia, frequent strokes with brain atrophy and necrosis of the basal ganglia (MRI). Desquamative skin lesions with alopecia. Tubular acidosis with progressive renal insufficiency (60% in case of mut0 ). 

Biology: ketoacidosis, hyperammonemia, hypoglycemia, ihyperglycinemia, sometimes neutropenia and thrombocytopenia. 

Treatment: low protein diet, oral carnitine and metronidazole (to decrease the intake of digestive propionates), bicarbonate, vitamin B12supplements. Liver transplantation sometimes associated with renal transplantation.

in case of hyperammonemia: contact the pediatrician of the child:

-        NH4 : 100-250 µmol/l: stop protein intake, glucose 10% IV (with insulin if necessary), Na benzoate (250 mg/kg in 2 h then 250 mg/kg/day) + carnitine (100 mg/kg and 100 mg/kg/day) (+ vitamin B12 1 mg/day, in case of vitamin B12 sensitive form); in case of hyperglycemia with increased lactates, lower the carbohydrate intake; monitor osmolality

-        NH4 : > 250-500 µmol/l: idem + Na phenylbutyrate and prepare extracorporeal detoxification (hemofiltration or peritoneal dialysis) if NH4 does not diminish quickly

Be careful: liver transplantation does not completely correct the metabolic problem because the enzyme deficiency remains present in other tissues (muscles): the blood levels of NH4 remain, therefore, higher than normal and these patients should continue to observe a special diet with supplements of carnitine; by caution, observe the same perianesthesia precautions as before transplantation. 

 Anesthetic implications: 

check complete blood count, NH4 blood level (postpone surgery elective if > 100 µmol/l) and renal function (risk of hyperkalemia and renal failure in presence of a resistance to vit B12; limitations of the preoperative fasting by administering an  electrolytic glucose-containg solution from the start of the fasting period: ensure a glucose intake of 8-10 mg/kg/min in infants and 5-6 mg/kg/min in adolescents; continue intake of carnitine (100 mg/kg/day) and give 1 mg of vitamin B12 if it is a sensitive form; avoid IV infusions containing lactate; continue the anti-epileptic treatment and avoid valproate; empty the stomach following any surgery exposing to swallowed blood (ENT surgery, stomatology) to avoid any hidden protein intake by the digestive tract. Special monitoring: ammonemia, glucose, lactate, blood gases ; provide anesthesia reducing the perioperative stress responses: regional anesthesia, morphine; avoid N2O ; avoid possible sources of propionic acid: propofol (soybean oil fatty acids), myorelaxants that undergo esterification (atracurium, mivacurium) because their metabolism produces organic acids, and propionic NSAIDs (ibuprofen, naproxen) .

References : 

• Sharar SR, Haberkern CM, Jack R, Scott CR. 
   Anesthetic management of a child with methylmalonyl-Coenzyme A mutase deficiency. 
  Anesth Analg 1991; 73: 499-501.
• Ho D, Harrison V, Street N. 
  Anaesthesia for liver transplantation in a patient with methylmalonic acidemia. 
  Paediatr Anaesth 2000; 10: 215-8.
• Baumgartner MR, Hörster F, Dionisi-Vici C et al. 
  Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. 
  Orphanet J Rare Diseases 2014; 9:130 (38 p)
• Niemi A-K, KIM IK, Krueger CE, Cown TM, Baugh N et al. 
  Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation. 
  J Pediatr 2015; 166 : 1455-61.
• Baba C, Kasahara M, Kogure Y, Kasuya S, Ito S et al.
  Perioperative management of living-donor liver transplantation for methylmalonic academia.
  Pediatr Anesth 2016, 26: 694-702.
• Morita J, Ito Y, Koga Y, Yano S et al.
  Persistent hyperkalaemia in vitamin B12 unresponsive methylmalonic acidaemia.
  J Inher Metab Dis 1989; 89-93.
• Chao P-W, Chang W-K, Lai I-W et al.
  Acute life-threatening arrhythmias caused by severe hyperkalzaemia after induction of anesthesia in an infant with methylmalonic acidemia.
  J Chin Med Assoc 2012; 75: 243-5.
• Kloesel B, Holzman RS.
  Anesthetic management of patients with inborn errors of metabolism.
  Anesth Analg 2017; 125: 822-236

Updated: September 2017*