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Propionic acidemia
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Prevalence: 1/350,000. Autosomal recessive transmission. Metabolic disorder due to a deficiency of the mitochondrial enzyme propionyl-CoA-carboxylase whose genes are located on chromosomes 3 and 13. This enzyme is involved in the catabolism of odd fatty acids, cholesterol and the amino acids threonine, methionine, isoleucine, and valine. The accumulation of propionyl-CoA inhibits the synthesis of N-acetylglutamate, which mediates the transformation of NH3 in urea, explaining the risk of hyperammonemia. On the other hand, the accumulation of propionic acid causes ketoacidosis. Another source of propionic acid is the anaerobic fermentation of odd fatty acids in the digestive tract.
The clinical manifestations are metabolic crises with ketoacidosis caused by an excessive intake of protein or infection. One can also observe: convulsions, hypotonia, hyperammonemia, coma, bone marrow dysfunction, osteopenia, pancreatitis. Dilated, more rarely congestive cardiomyopathy may appear (23%) (average age: 7 years) which seems unrelated to the quality of the medical care: it is reversible after an orthotopic or auxiliary liver transplant. A QTc prolongation may also appear.
Treatment: avoid fasting, diet with proteins low in threonine, methionine, isoleucine, and valine; carnitine supplements (50 - 100 mg/kg/day) (to facilitate the elimination of propionic acid) and biotin. Sometimes chronic metronidazole.
in case of hyperammonemia: according to child's pediatrician opinion:
- 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/d, if sensitive form); in case of hyperglycemia with increase in lactates, lower the carbohydrate intake; monitor osmolality and osmolality
- NH4 : > 250-500 µmol/l: idem + phenylbutyrate and prepare for extracorporeal detoxification (hemofiltration or peritoneal dialysis) if NH4 does not diminish quickly
Anesthetic implications:
- avoid prolonged fasting and hypoglycemia (cause of protein catabolism): administer an electrolytic solution with glucose 10 % early from the start of the fasting period (aim for a glucose supply of 8-10 mg/kg/min in infants to 5-6 mg/kg/min in adolescents);
- postpone elective surgery if NH4 > 100 µmol/l
- check Hb, platelet and cardiac function (ultrasound, ECG for QTc)
- give the usual dose of carnitine (50 - 100 mg/kg/day) the day of the intervention
- insert a pharyngeal packing and empty the stomach in case of surgery exposing to the deglution of blood (ENT, stomatology) to avoid any hidden protein intake through the digestive tract
- special monitoring: blood glucose, NH4, blood gases
- avoid possible sources of propionic acid: propofol (soybean oil fatty acids), myorelaxants undergoing esterification (atracurium, mivacurium...) because their metabolism produces organic acids, propionic NSAIDs (ibuprofen, naproxen). Ketorolac can be used.
References :
- Harker HE, Emhardt JD, Hainliner BE.
Propionic acidemia in a four-month-old male: a case study and anesthetic implications.
Anesth Analg 2000; 91: 309-11.
- Romano S, Valayannopoulos V, Touati G, Jais JP, Rabier D, De Keyzer Y, Bonnet D, de Lonlay P.
Cardiomyopathies in propionic aciduria are reversible after liver transplantation.
J Pediatr 2010 ; 156 : 128-34.
- 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)
- Rajakumar A, Kaliamoorthy I, Reddy MS, Rela M.
Anaesthetic considerations for liver transplantation in propionic acidemia.
Indian J Anaesth 2016; 60:50-4
Updated: Octobre 2018