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