[MIM 231 680]

(Dicarboxylic Aciduria, deficiency of multiple acyl - CoA Dehydrogenase MADD)

Estimated incidence of 1/20,000 births.

From a genetic point of view, this is the autosomal recessive  transmission of a mutation of the

• ETFA gene (electron transfer flavoprotein alpha polypeptide) (15q24.2-q24.3) that causes glutamic aciduria type A
• ETFB gene (electron transfer flavoprotein beta polypeptide) (19q13.41) that causes glutamic aciduria type B
• EFTDH gene (electron transfer flavoprotein polypeptide dehydrogenase) (4q32.1) that causes glutamic aciduria type C.

Mitochondrial cytopathy due to a disorder of the β-oxidation of the fatty acids and of the metabolism of choline: dysfunction or absence of one of the flavoproteins that transfer the electrons from the flavine-adenine-dinucleotide to CoenzymeQ in the respiratory chain. This anomaly causes an accumulation of fatty acids in the plasma and an inability to use the lipids as source of energy (ATP).

From a clinical point of view, depending on the residual activity of the mutated flavoprotein, one distinguishes:

• MADD type I: lethal neonatal form with congenital malformations: facial dysmorphism (hypertelorism, bulging forehead), polycystic kidneys, abdominal wall abnormalities,  pulmonary hypoplasia, cholestasis
• MADD type II: neonatal form without birth defects: hypoglycemia and metabolic acidosis without ketosis, lactic acidosis  (sometimes hyperammonemia) often caused by metabolic stress (infection, fever, fasting, exercise, surgery),  hepatomegaly, urine with a "foot smell",  hypertrophic cardiomyopathy and muscular hypotonia (inclusions of lipid droplets
• MADD type III: late form (partial deficit): hypoglycemia without ketosis, seizures, fatty liver disease, hepatomegaly, urine with a "foot smell,"  hypotonia due to myopathy (inclusions of lipid droplets at biopsy) with elevated CPK, sometimes cardiomyopathy or crises of rhabdomyolysis.

Treatment:

• type II: low-fat and -protein diet, avoid hypoglycemia (nocturnal feeding), riboflavin,  L-carnitine;  high doses of  oral hydroxybutyrate
• type III: riboflavin, L carnitine, CoQ

Anesthetic implications: 

ECG and echocardiography. Check kidney and liver function as well as basal levels of lactate, glucose, CPK. Risk of hypoglycemia:  short fasting period with infusion of an electrolytic solution with 5 or 10 % glucose unless the child is stable and the duration of preoperative fasting is less than 2 hours. Avoid continuous infusion of propofol (respiratory chain inhibition and lipid overload)  and succinylcholine.

References : 

-        Farag E, Argialous M, Narouze S, DeBoer GE, Tome J. 
The anesthetic management of ventricular septal defect repair in a child with mitochondrial cytopathy. 
Can J Anesth 2002; 49: 958-62.

-        Prasad M, Hussain S. 
Glutaric aciduria type II presenting as myopathy and rhabdomyolysis in a teenager. 
J Child Neurol 2015; 30: 96-9 

-        Lilitsis E, Astirakaki E, Blevrakis E, Xenaki S, Chalkiadakis G, Chrysos E.
Anesthetic management of a pediatric patient with Electron Transfer Flavoprotein Dehydrogenase deficiency (ETFDH) and acute appendicitis: case report and review of the literature.
BMC Anesthesiology 2017; 17 :116. DOI 10.1186/s12871-017-0400-9

Updated: October 2020