Discussion
Congenital disorders of glycosylation (CDG) comprise over 130 rare metabolic disorders via mutations in specific genes that often impact multiple organ systems. The process of glycosylation occurs when a carbohydrate is attached to a protein or lipid, leading to the formation of glycoproteins and glycolipids, respectively. Both glycoproteins and glycolipids have important functions in all tissues and organs and a deficiency can lead to consequences throughout the body.2 Specifically, the mutation in the gene ALG-13 affects N-linked glycosylation which can disrupt various metabolic pathways and often manifests as microcephaly, hepatomegaly, seizures, developmental delay, and generalized hypotonia.3 The incidence and prevalence of CDG is less than 1 in 1,000,0004 and spans worldwide to almost every ethnic background and affects both sexes equally.5 Most CDG conditions follow an autosomal recessive inheritance, but the large variety can include autosomal dominant or X-linked inheritance.2 ALG-13, located on the X-chromosome, is typically a new genetic mutation or follows a X-linked recessive inheritance.6 To date, there are no specific guidelines for anesthetic management in CDG patients and there are few case reports outlining optimal or successful management. This case demonstrates a safe and successful anesthetic in a patient with CDG while exemplifying the importance of taking all aspects of a patient’s presentation and history into consideration when identifying an optimal anesthetic plan.
Due to a positive family history of MH, triggering agents such as volatile anesthetics and succinylcholine were avoided for management.7 To adequately purge the anesthesia machine of volatile anesthetics, the machine was flushed as specified above. While volatile anesthetics such as sevoflurane and isoflurane can trigger MH, nitrous oxide is not a triggering agent for MH. Often a total intravenous anesthetic (TIVA) is utilized to avoid MH triggers8; however, for a pediatric patient, nitrous oxide is a helpful sedative which can be administered via inhalation while intravenous access is yet to be obtained.9,10Additionally, there is no known interference between nitrous oxide and the glycosylation process.
While there are no known contraindications for succinylcholine use in patients with CDG, it is a triggering agent for MH. Rocuronium, a non-depolarizing neuromuscular blocker, and sugammadex, a potent binding reversal agent, were used for neuromuscular blockade and reversal, respectively.10,11 Propofol can interfere in glycosylation pathways and studies caution against its use in CDG patients due to potential adverse effects, thus we opted to avoid propofol throughout the anesthetic management.12
Two other agents considered were ketamine and dexmedetomidine. Both ketamine and dexmedetomidine have an unknown impact on the glycosylation process. Ketamine has been considered controversial in patients with a history of seizures or epilepsy, although studies do not support avoidance. We kept ketamine in mind as an alternative agent. Dexmedetomidine, as an alpha-2 agonist, can cause bradycardia due to its sympatholytic effect.13 Since the pediatric patient was bradycardic on induction, dexmedetomidine was avoided. Remifentanil infusion has been shown to reduce postoperative nausea and vomiting and provide faster recovery in patients with CDG and was used successfully in this patient.12 For pain management, fentanyl was used; acetaminophen was considered but was not used due to potential harmful impact on hepatic function.10
Due to development of craniofacial abnormalities, CDG patients can present as a potential difficult airway and must be evaluated. The definition of a difficult airway by the Pediatric Difficult Intubation registry includes 1) failure to visualize vocal cords on direct laryngoscopy (DL) by an experienced provider, 2) impossible DL due to abnormal anatomy, 3) failed DL within the last 6 months or 4) DL felt to be harmful in a patient with suspected difficult laryngoscopy.14 A primary anatomic concern for CDG is the development of microcephaly which raise concerns for difficult laryngoscopy due a narrow mouth opening, limited mobility of the mandible, and small palate. Options outside of direct laryngoscopy include video laryngoscopy, supraglottic airway, and flexible fiberoptic bronchoscope and optical stylet with the fiberoptic bronchoscope currently considered the gold standard for difficult airway management in pediatric patients.14 In the event of inability to intubate and inability to ventilate in a pediatric patient, surgical access through the cricothyroid membrane or anterior tracheal wall is an emergent option. The surgeon, an otolaryngologist, was present for induction during our case, and it is important to have a physician able to perform surgical access present throughout induction and peri-intubation for any pediatric patient considered a possible difficult airway.
Key Words: congenital disorders of glycosylation, pediatric anesthesia, malignant hyperthermia