Perioperative Management of Type-3c Gaucher's Disease for Kyphoscoliosis Correction and Spinal Cord Detethering

Abstract

Gaucher's disease (GD) is an inherited lysosomal storage disorder caused by mutations in the acid β-glucosidase (GBA) gene, leading to abnormal function of the enzyme glucocerebrosidase, which results in the accumulation of glucocerebrosides in various organs, causing multiorgan dysfunction. GD has three phenotypes, of which type-3 is the cardiovascular type with many anesthetic implications. A 20-year-old woman, genetically proven type-3 GD, was diagnosed with thoracolumbar kyphoscoliosis with fatty filum and planned for deformity correction and fatty filum excision. She had mitral and aortic stenoses, hydrocephalus, corneal opacity, a difficult airway, and chronic pain. Management of a difficult airway, hemodynamic management in double stenotic lesions, and perioperative pain management were considered as some of the challenges. The intraoperative course was complicated by massive blood loss and pneumothorax, which were managed appropriately. Perioperative pain was managed using a multimodal analgesic technique. Thorough preoperative evaluation, meticulous planning, and execution with adequate backup plans and appropriate pain management helped with faster recovery.

 

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Keywords

aortic stenosis - type-3c Gaucher's disease - kyphoscoliosis correction - mitral stenosis - massive blood loss and transfusion

Introduction

Gaucher's disease (GD) is an inherited lysosomal storage disorder caused by mutations in the acid β-glucosidase (glucocerebrosidase) gene, leading to the accumulation of glucocerebroside in the liver, spleen, lungs, bone marrow, and central nervous system.[1] [2] [3] Patients with GD may present with anemia, thrombocytopenia, osteopenia, pathological fractures, vertebral body collapse, upper airway obstruction, and neurodegenerative symptoms due to glucocerebroside accumulation.[4] [5] Based on the age of onset, central nervous system involvement, and disease progression, it is classified into three phenotypes (types 1–3).[1] [2] [3] Type-3 GD has many subtypes, of which type-3c has many anesthetic implications. Anesthetic management of a type-3c GD is scarcely reported; here, we report the perioperative management of a patient with type-3c GD for kyphoscoliosis correction and spinal cord detethering.

 

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Case Report

A 20-year-old American Society of Anesthesiologists (ASA)-2 woman (height 143 cm, weight 43 kg, body mass index 20.5 kg/m²), known case of type-3c GD, presented with low back pain (numerical rating scale [NRS] 8) radiating to the right leg (NRS 10) and right shoulder deformity, restricted mouth opening due to severe neck pain. Central nervous system examination revealed kyphoscoliosis involving the thoracic spine with a curve to the right (Cobb angle 40 degrees) with severe paraspinal muscle spasm and lower limb spasticity. Her single breath count was 20, and the chest expansion was 1.5 cm. Cardiovascular examination revealed an ejection systolic murmur (aortic area) and mid-diastolic murmur (mitral area). Airway examination revealed a short web neck, large tongue, restricted mouth opening (inter-incisor distance 2 cm), and severe limitation of neck movement (severe pain induced). She also had corneal opacity involving the left eye with decreased visual acuity. Magnetic resonance imaging of the spine revealed C5–C6 block vertebra, T9-right hemivertebra, thoracic kyphoscoliosis (T4–T12, apex at T8–T9) convexity to the right, with fatty filum terminale (L2–L5). Transthoracic echocardiography revealed moderate mitral stenosis with dilated left atrium and mild aortic stenosis with normal ventricular function. She was taking metoprolol, diuretics, phenoxy methyl penicillin, and multiple pain medications. Blood investigations revealed isolated factor XII deficiency with increased activated partial thromboplastin time (aPTT). She was scheduled for L5-laminectomy, sectioning of the fatty filum, and kyphoscoliosis correction with motor-evoked potential (MEP) monitoring. Difficult airway, hemodynamic management in prone position with double stenotic valvular lesion, management of massive blood loss and transfusion, spinal cord protection, and pain management are some of the anticipated anesthetic challenges.

On the day of surgery, standard ASA monitors were connected, and wide-bore peripheral and arterial lines were established. The patient was induced with fentanyl (2 mcg/kg), propofol (target-controlled infusion Schnider model at a concentration of 3.5 mcg/mL), ketamine (0.5 mg/kg), preservative-free lignocaine (1.5 mg/kg), and phenylephrine (50 mcg). After confirmation of mask ventilation, the patient was paralyzed with atracurium (0.5 mg/kg), and asleep fiberoptic intubation was performed using a 7.0-mm endotracheal tube. Anesthesia maintenance was with propofol (target concentration 2–2.5 mcg/mL), titrated to bispectral index of 40 to 50, fentanyl (1–2 mcg/kg/h), and ketamine (0.1 mg/kg/h) to facilitate MEP monitoring. Tranexamic acid was administered (15 mg/kg bolus, followed by 5 mg/kg every 3 hours) to reduce blood loss.

The intraoperative course was complicated by massive blood loss (2,000 mL), transfusion-associated nonhemolytic allergic reaction, and iatrogenic pneumothorax (right side). Blood loss was replaced with packed red blood cells (4 units), fresh frozen plasma (2 units), and cryoprecipitate (4 units). Administration of blood and blood products was guided by hemodynamic parameters, pulse pressure variation, serial measurements of lactate and hemoglobin, as well as urine output. Her hemodynamics were maintained within 10 to 15% of baseline using noradrenaline at a rate of 0.05 to 0.15 mcg/kg/min. A transfusion-associated nonhemolytic allergic reaction was treated with chlorpheniramine, hydrocortisone initially followed by a low-dose adrenaline infusion (0.03–0.05 mcg/kg/min), which was stopped after an hour. Pneumothorax was managed with intercostal drainage placement. At the end of surgery, the patient was extubated and shifted to the intensive care unit with noradrenaline support (0.1 mcg/kg/min), which was gradually tapered and stopped over 8 hours. Postoperative pain was managed using continuous epidural morphine infusion (130 mcg/h) and low-dose intravenous ketamine (0.1 mg/kg/h) and paracetamol (750 mg every sixth hour), ketorolac (30 mg every eighth hour), and tramadol (50 mg as rescue analgesia). She experienced complete resolution of radicular pain (right lower limb) and back pain following surgery, and there was a significant reduction in intake of pain medication. She was able to ambulate with minimal support by the third postoperative day and was discharged in stable neurological condition on the seventh postoperative day.

 

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Discussion

Type-1 GD is a nonneuronopathic/adult type, most prevalent, with clinical manifestations involving the hematopoietic, skeletal system, and visceral organs. Types-2 and 3 GD are a neuronopathic type with early involvement of the central nervous system and differing rates of neurological deterioration. Type-2-GD-infantile form, present during infancy, rapidly deteriorates, and children die within 2 years of diagnosis. Type-3 GD is a subacute/chronic neuronopathic/juvenile form with various subtypes encompassing a spectrum of neurological (GD3a), internal organ and skeletal system (GD3b), cardiovascular, and ophthalmological (GD3c) abnormalities, and has a more protracted course.[3] [6] [7]

Our patient was diagnosed with cardiovascular type-3c GD based on genetic testing and clinical presentation. It has an incidence of <1/100,000 births and constitutes ∼5% of all GD cases with diverse presentations involving various systemic organs.[7] [8] Cardiovascular and ophthalmic manifestations include stenosis/regurgitation of aortic and mitral valves (due to calcification), ascending aorta calcification/fibrosis, corneal opacities, ophthalmoplegia, strabismus, saccadic eye movements, and supranuclear gaze palsy. Neurological symptoms included borderline intelligence, ventriculomegaly, thin corpus callosum, leptomeningeal thickening, hyperreflexia, hyporeflexia, seizures, spastic paraplegia, and sensorineural hearing loss. Visceral and hematological system involvement manifests as hepatosplenomegaly, anemia, and thrombocytopenia.[7] [9] [10] We summarized our patient findings on type-3c GD and its anesthetic significance in [Table 1].

Table 1 Summary of various system involvement in our patient concerning type-3c GD and its anesthetic challenges

System involvement	Main findings	Anesthetic management
Cardiovascular	Mitral and aortic stenosis	Maintaining hemodynamics close to baseline with adequate preload and maintenance of afterload with vasopressor
Ophthalmological	Corneal opacity	Careful positioning of eyes without compression to prevent vision loss Avoiding excessive crystalloid administration and anemia by appropriate fluid and blood administration
Neurological	Communicating hydrocephalus, hyperreflexia, spasticity of lower limbs	Total intravenous anesthesia to avoid further increase in ICP
Musculoskeletal	Kyphoscoliosis	Kyphoscoliosis and untethering under MEP monitoring. Keeping all prerequisites to facilitate MEP monitoring and to prevent MEP-related complications
Airway	Difficult airway—restricted mouth opening and neck extension, enlarged oropharyngeal soft tissue	Asleep fiberoptic intubation after checking the adequacy of mask ventilation
Hematological	Factor XII deficiency (not related to type-3c GD) No anemia and thrombocytopenia were noted in our case	Nil intervention

Abbreviations: GD, Gaucher's disease; ICP, intracranial pressure; MEP, motor-evoked potential.

Maintaining cardiac output with a double stenotic valvular lesion, in the prone position with a massive blood loss scenario, is one of the biggest anesthetic challenges.[11] [12] Maintenance of preload and afterload, and avoidance of myocardial depression and tachycardia were the main goals. In our case, tachycardia (heart rate >120/min) accompanied by hypotension, despite effective analgesia and adequate fluid resuscitation, led us to suspect a transfusion-associated nonhemolytic allergic reaction, which was later confirmed by the presence of wheals and rashes throughout the body. While the use of adrenaline is generally discouraged in patients with double stenotic valvular lesions due to its β-1 adrenergic effects, in this instance, the timely administration of a low-dose adrenaline infusion proved beneficial in reducing heart rate and restoring blood pressure.

Coagulation abnormalities are common in patients with GD due to thrombocytopenia, abnormal platelet function, decreased production of coagulation factors, and activation of fibrinolysis.[13] Our patient had isolated (aPTT elevation due to factor XII deficiency, which did not warrant any treatment. Tranexamic acid was administered to reduce blood loss. Massive blood loss was treated with the timely administration of blood and blood products, and avoiding hypothermia, acidosis, and hypocalcemia.

Upper airway obstruction is common in patients with GD due to infiltration of glycolipids.[5] In our case, a large tongue, redundant soft tissue at the oropharynx, tonsillar enlargement (due to glycolipid accumulation), restricted mouth opening, and neck extension (tethering-related) predicted the airway as difficult. Hence, we planned fiberoptic bronchoscope–guided intubation under anesthesia and paralysis after ensuring adequate mask ventilation.

Patients with GD often present with kyphoscoliosis due to vertebral fractures resulting from infiltration of Gaucher cells and chronic osteopenia, presenting with chronic pain. Pain management in the presence of chronic pain is another challenging aspect while managing these cases. As suggested in the literature, multimodal analgesia using various drugs, acting via different mechanisms, helped her to recover faster.[14]

 

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Conclusion

Multiorgan involvement and associated systemic illnesses make anesthetic management challenging in patients with GD. A multidisciplinary team approach with extensive preoperative evaluation, thorough optimization, meticulous anesthesia and surgical techniques, careful postoperative monitoring, and optimal pain management helped for a better outcome in this case.

 

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Conflict of Interest

None declared.

• References

• 1 Kaplan P, Andersson HC, Kacena KA, Yee JD. The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med 2006; 160 (06) 603-608
• 2 Grabowski GA. Recent clinical progress in Gaucher disease. Curr Opin Pediatr 2005; 17 (04) 519-524
• 3 Rosenbloom BE, Weinreb NJ. Gaucher disease: a comprehensive review. Crit Rev Oncog 2013; 18 (03) 163-175
• 4 Grass A, Riemer E, Zimran A. et al. Anesthetic approaches and perioperative complications of total hip arthroplasty in Gaucher disease: a control-matched retrospective-cohort study. Life (Basel) 2023; 13 (08) 1716
• 5 Tobias JD, Atwood R, Lowe S, Holcomb III GW. Anesthetic considerations in the child with Gaucher disease. J Clin Anesth 1993; 5 (02) 150-153
• 6 Abrahamov A, Elstein D, Gross-Tsur V. et al. Gaucher's disease variant characterised by progressive calcification of heart valves and unique genotype. Lancet 1995; 346 (8981) 1000-1003
• 7 Wang YZ, Li TT, Cao HL, Yang WC. Recent advances in the neuroprotective effects of medical gases. Med Gas Res 2019; 9 (02) 80-87
• 8 Sun A, Chang IJ, Lam C, Berry GT. Lysosomal Storage Disorders. In Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics, 7th edition.. Academic Press; 2021: 563-682
• 9 Kurolap A, Del Toro M, Spiegel R. et al. Gaucher disease type 3c: new patients with unique presentations and review of the literature. Mol Genet Metab 2019; 127 (02) 138-146
• 10 Bulut FD, Kor D, Kılavuz S. et al. Expanding the phenotypic landscape of Gaucher disease type 3c with a novel entity - transient neonatal cholestasis. Eur J Med Genet 2023; 66 (06) 104764
• 11 Unger P, Pibarot P, Tribouilloy C. et al; European Society of Cardiology Council on Valvular Heart Disease. Multiple and mixed valvular heart diseases. Circ Cardiovasc Imaging 2018; 11 (08) e007862
• 12 Ng JH, Leonard I. Managing multiple valvular disease in spine surgery: A case report. JCA Advances 2025 2. 02
• 13 Rosenbaum H. Hemorrhagic aspects of Gaucher disease. Rambam Maimonides Med J 2014; 5 (04) e0039
• 14 Seki H, Ideno S, Ishihara T, Watanabe K, Matsumoto M, Morisaki H. Postoperative pain management in patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis: a narrative review. Scoliosis Spinal Disord 2018; 13: 17

Publikationsverlauf

Artikel online veröffentlicht:
22. August 2025