[MIM 243 500]

(isovaleric aciduria)

Very rare: 1/100.000. Autosomal recessive disorder of metabolic disease whose clinical presentation is very variable. Subjected in many countries to a neonatal screening. Disturbance of the metabolism of branched chain amino acids (leucine, isoleucine, valine)  following a deficiency of isovaleryl-CoA dehydrogenase, an  intramitochondrial enzyme which participates in the respiratory chain.

-        severe neonatal onset form: progressive encephalopathy beginning with ketosis or ketoacidosis, vomiting, abnormal movements, coma, hyperammonemia

-        delayed or intermittent form: metabolic crisis during an infection or following an important intake of protein

-        chronic and progressive form : severe hypotonia, developmental delay, severe

-        hepatic form: Reye-like syndrome: hepatic coma with cerebral edema, acute fatty liver

-         gastrointestinal form: anorexia with aversion to proteins, frequent vomiting, osteoporosis.

Clinical signs: the patient has an "foot smell" in case of catabolic stress.

Treatment: diet low in proteins and administration, p os, of glycine (150 - 300 mg/kg/day in 4 doses) and L-carnitine (50 - 100 mg/kg/day in 4 doses) that enable to eliminate isovaleric acid by binding it. 

Risk of brutal decompensation in case of metabolic stress: fever, diarrhea, prolonged fasting.

Prompt treatment of these crises is necessary to avoid neurological sequelae (acute cerebral edema) or death: glucose infusion, restriction of protein intake, intake of glycine and carnitine, sometimes  peritoneal dialysis. Risk of acute pancreatitis during the metabolic crises.

 Anesthetic implications: 

Special diet. Usual dose of carnitine the day of intervention; carnitine deficiency increases the risk of toxicity of local anesthetics ! Avoid any hypoglycemia: limit the duration of preoperative fasting and administer a glucose-containing solution (5 or even 10%) as soon as the fasting period begins.

In case of surgery where blood can be swallowed (ENT surgery, stomatology), empty the stomach to prevent a protein intake by digestive tract. In case of vomiting: check blood glucose and the ammonium levels.

References : 

• Ogier de Baulny H, Dionisi –Vici C, Wendel U. 
  Branched-chain organic acidurias/acideaemis, In Inborn metabolic diseases, Saudubray J-M, van den Berghe G, Walter JH. 5th edition, Springer 2011, p 277-96
• Weinberg GL, Laurito CE, Gelner P, Pygon BH, Burton BK. 
  Malignant ventricular dysrhythmias in a patiet with isovaleric acidemia receiving general and local anesthesia for suction lipectomy. 
  J Clin Anesth 1997; 9: 668-70.
• Lam H, Kiberenge R, Sobey JH, Austin T. 
  Anesthetic management of a patient with isovaleric acidemia. 
  A&A Case reports 2015; 4:37-8.
• Kelkar KV, Gadre VN.
  Case of isovaleric acidaemia for cataract surgery.
  Indian J Anaesth 2016; 60:427-9

Updated June 2016