NM-249
Anesthetic management for a child with QARS gene mutation
Lin T, Wuenstel A, Tkachenko I
University of Chicago Medicine, Chicago, IL, United states
Introduction
The QARS gene codes for glutaminyl-tRNA synthetase (QARS), which attaches glutamine to its tRNA in cytoplasm and mitochondria[1]. It is anti-apoptotic and required for dendritic and axonal terminal arborization during development[1,2]. QARS gene mutation results in progressive microcephaly, diffuse brain atrophy, early-onset epileptic encephalopathy, and severe hypotonia[2,3].
Case Report
5-month-old 5kg girl with heterozygous QARS gene mutation manifested by microcephaly, neonatal intractable epilepsy, and central hypotonia was scheduled for laparoscopic G-tube placement, direct laryngoscopy, and bronchoscopy. She had microcephaly, micrognathia, and central hypotonia with poor head control. Respiratory exam was significant for biphasic stridor and bilateral rhonchi. She was on 6L HFNC for frequent apnea and desaturation with seizures.
In the OR, patient underwent modified RSI with 0.75mg midazolam, 15mcg fentanyl, and 9mg rocuronium. She was easily intubated with 3.0 microcuffed ETT by Miller 1 blade with Grade 2 view. Maintenance was achieved with 1mcg/kg/hr dexmedetomidine and 0.1-0.15mcg/kg/min remifentanil. 2.5mg dexamethasone was given to minimize airway edema. After the surgery, neuromuscular blockade was reversed with 0.35mg neostigmine and 0.07mg glycopyrrolate and patient was extubated successfully. No anatomical airway abnormalities were found. Patient’s stridor was attributed to poor muscle tone and airway collapse.
Discussion
QARS gene mutation has several anesthetic implications. First, microcephaly and facial dysmorphism may pose as difficult airway requiring advanced intubation techniques. Patients have increased aspiration risk due to hypotonia and pharyngeal dysphagia. Poor respiratory muscle tone also causes airway collapse, decreased FRC, and increased risk of respiratory infections.
Second, hypotonia increases the risk of life-threatening hyperkalemia with succinylcholine administration. We also avoided volatile anesthetics for possible increased risk of malignant hyperthermia (MH). MH is associated with many disorders characterized by congenital myopathy and hypotonia including central core disease and King-Denborough syndrome[4].
Lastly, we avoided propofol in our TIVA due to possible increased risk of propofol infusion syndrome (PRIS). PRIS is associated with younger age, severe critical illness of CNS/respiratory origin, and subclinical mitochondrial disease[5]. As QARS participates in protein translation in mitochondria, potential mitochondrial disease may predispose our patient to PRIS.
Conclusion
QARS gene mutation is a rare genetic disorder characterized by progressive microcephaly, diffuse brain atrophy, early-onset epileptic encephalopathy, and severe hypotonia. Anesthetic management of patients with this disorder presents challenges including airway management and choice of maintenance to avoid risks of MH and PRIS.
References
1. Antonellis A, Green E. Annu Rev Genomics Hum Genet. 2008;9:87-107
2. Zhang X et al. The American Journal of Human Genetics. 2014;94:547-558
3. Kodera H et al. Journal of Human Genetics. 2015;60:97-101
4. Rosenberg H et al. Orphanet Journal of Rare Diseases. 2015;10(93)
5. Kam P, Gardone D. Anaesthesia. 2007;62:690-701
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