[MIM 213 670]

(glutaric aciduria type I, glutaryl-CoA dehydrogenase deficiency)

Prevalence: 1/50,000 births. Mitochondrial cytopathy due to the autosomal recessive transmission of a mutation in the GCDH gene (19p13.2) leading to a deficiency in glutaryl-CoA dehydrogenase. That enzyme is involved in the metabolism of lysine, hydrolysine and tryptophan. This enzymatic deficiency results in the accumulation of hydroxyglutaric, glutaconic, glutaric and bicarbonic acids as well as glutaryl-carnitine. 3-hydroxyglutaric acid acts as a toxin that inhibits mitochondrial metabolism, resulting in abnormal intracellular calcium homeostasis. This pathology is one of the targets of neonatal screening in most developed countries.

In the absence of preventive treatment, symptoms appear in the perinatal period or between 4 and 15 months of age in 3/4 of cases: moderate hypotonia is present at birth but the diagnosis is established in case of crisis of acute encephalopathy with loss of consciousness and sometimes convulsions. Glutaric acid and 3-hydroxyglutaric acid accumulation causes progressive dystonia with mental retardation, choreoathetosis and dysarthria. Without treatment, the disease progresses to a chronic encephalopathy with psychomotor delay and spastic quadriparesis. 

However, even in case of a well applied treatment, metabolic crises with hypoglycemia and ketoacidosis can occur during catabolic situations (infection, fever, fasting, perioperative period, postpartum) or secondary to carnitine deficiency. 

Brain damage is localized at the level of the basal ganglia (necrosis). Macrocephaly of postnatal onset is often seen with hydrocephalus and sometimes subdural fluid collection or arachnoid cysts. 

Symptomatic treatment:  low lysine and tryptophan diet, supplements of carnitine 100 mg/kg/day (because there is a secondary carnitine deficiency), riboflavine100 to 200 mg/day

 Anesthetic implications: 

Risk of inhalation of gastric contents. Risk of hypoglycemia.  Provide IV electrolytic glucose-containing fluid from the onset of the preanesthetic fasting and until resumption of normal diet. IV carnitine supplements. Avoid a continuous infusion of propofol because of a potential increased risk of PRIS ? Avoid medications that can have  extrapyramidal effects (droperidol, metoclopramide) because they can interfere with postoperative neurological monitoring. In case of seizures, avoid Na valproate. Take care to avoid hidden sources of protein intake: in case of blood swallowing (ENT surgery, stomatology), empty the stomach content to prevent any hidden protein intake from the digestive tract; avoid fresh frozen plasma; check (lysine, tryptophan) protein content of the IV solutions (eg parenteral nutrition or priming of the CPB in cardiac surgery).

References : 

• Hernandez-Palazon J, Sanchez-Rodenas L, Martinez-Lage JF, Castano-Collado I. 
  Anesthetic management in two siblings with glutaric aciduria type I. 
  Pediatr Anesth 2006 ; 16 : 188-91.
• Tsiotou AG, Malisiova A, Bouzelos N, Velegrakis D. 
  The child with glutaric aciduria type I: anesthetic and perioperative management. 
  J Anesth 2011; 25:301-4.
• Ituk US, Allen TK, Habib AS. 
  The peripartum management of a patient with glutaric aciduria type I. 
  J Clin Anesth 2013, 25:141-5
• Kölker S, Eichhorn J, Sebening C, Klein B et al. 
  Perioperative management of a child with glutaric aciduria type I undergoing cardiac surgery. 
  A&A Case Reports 2013; 1: 5-7
• Teng W-N, Lin S-M, Niu D-M, Kuo Y-M et al.
  Anesthetic management of comprehensive dental restoration in a child with glutaric aciduria type I using volatile sevoflurane.
  J Chin Med Assoc 2014; 77: 548-51

Updated September 2017