Anesthetic Considerations for a Patient with

Mucolipidosis type III Intermediate and Chiari I Malformation

Nathan Kor, M.D.1,Laurence Torsher, M.D.2

 

INTRODUCTION

This case discusses a patient with both mucolipidosis (ML) type

III intermediate and Chiari I malformation.

 

BACKGROUND

Mucolipidosis (ML) comprises a group of autosomal recessive

lysosomal storage disorders. Type II and III are caused by

mutations in GNPTAB or GNPTG, which encode N-

acetylglucosamine-1-phosphotransferase. This enzyme adds

the mannose-6-phosphate (M6P) tag directing hydrolases to

lysosomes. Loss of M6P tagging causes misrouting of hydrolases

to the extracellular space, leading to lysosomal substrate

accumulation and progressive tissue injury.

The mucolipidoses are divided into types I-IV, with type II (I-cell

disease) and III (pseudo-Hurler polydystrophy) sharing similar

pathophysiology. Type III intermediate represents a form

between the severe early-onset ML II and the milder ML III variant.

The coexistence of Chiari I malformation further complicates

care due to risks of cervical cord compression, increased

intracranial pressure, and restricted neck mobility.

PATIENT INFORMATION

Age / Sex: 21-year-old female presenting for right total hip

arthroplasty.

Past Medical History:

• Mild aortic regurgitation

• Mild mitral stenosis and prolapse

• History of difficult intubation

• Chiari I malformation

• Cervical stenosis

• Mild intellectual delay

• Mucolipidosis type III intermediate

Anesthesia / Surgical History:

• Adenotonsillectomy

• Left total hip replacement

• Prior difficult airway

 

CASE DESCRIPTION

The patient was premedicated with acetaminophen, celecoxib, midazolam, and a scopolamine patch. On examination, she

was Mallampati III with limited neck range of motion. One year prior, she had an uneventful video-laryngoscopic intubation.

General anesthesia was induced with fentanyl 100 µg, lidocaine 60 mg, propofol 100 mg, and rocuronium 50 mg.

Intubation was performed successfully using video-assisted laryngoscopy with minimal cervical extension. Anesthesia was

maintained with a propofol infusion, and phenylephrine was administered to manage transient hypotension. At the end of the

procedure, paralysis was reversed with sugammadex 2 mg/kg. Multimodal analgesia included ketamine 30 mg and

hydromorphone 0.6 mg. She received dual antiemetic prophylaxis with dexamethasone and ondansetron. The patient was

extubated uneventfully and spent one night in the hospital.

 

ANESTHETIC CONSIDERATIONS

Mucolipidosis

The primary concern in ML is the global stiffening of connective and soft tissues, leading to:

• Difficult airway due to limited cervical mobility and narrowed upper airway structures.

• Restrictive lung disease from chest wall rigidity and mucosal thickening.

• Cardiac valve abnormalities: thickening of the mitral (and less commonly aortic) valve, often presenting as regurgitation.

• Skeletal deformities (dysostosis multiplex): thoracic deformities, kyphosis, clubfoot, and abnormal long bones, which can

complicate regional anesthesia.

Chiari I Malformation

• Defined by downward displacement of the cerebellar tonsils (>4 mm) through the foramen magnum into the cervical

canal; often associated with syringomyelia or hydromyelia.

• 30–50% of patients exhibit fusion of the skull base with C1 or partial fusion of C1–C2.

• Special care is required in positioning and intubation to prevent neurological injury.

• Depending on severity, anesthesiologists should avoid maneuvers that increase intracranial pressure (ICP).

DISCUSSION

•ML II and III are rare, with an incidence of 0.22–2.7 per 100,000 live births.

•ML III results in slower progressive stiffening and thickening of tissues, affecting

the airway, cardiac valves, and skeletal system.

•Preoperative evaluation of pulmonary and cardiac function is essential,

anticipating progressive functional decline.

•Structural changes can lead to difficult mask ventilation and intubation, even in

patients with previously uneventful anesthetics, due to the progressive nature of

tissue deposition and musculoskeletal contractures.

•Chiari I malformations require careful airway management and avoidance of ICP-

elevating stimuli.

REFERENCES

Figure 1. Patient MRI with Chiari I

malformation

Figure 2. female with ML IIIα/β reproduced with

permission © 1993-2025 University of Washington

1. Ammer LS, Muschol NM, Santer R, et al. Anaesthesia-Relevant Disease

Manifestations and Perianaesthetic Complications in Patients with Mucolipidosis—A

Retrospective Analysis of 44 Anaesthetic Cases in 12 Patients. J Clin Med.

2022;11(13):3650. doi:10.3390/jcm11133650

2. American Association of Neurological Surgeons. Chiari Malformation. Available at:

https://www.aans.org/patients/conditions-treatments/chiari-malformation/

3. Dogterom EJ, Wagenmakers M, Wilke M, et al. Mucolipidosis Type II and Type III:

A Systematic Review of 843 Published Cases. Genet Med. 2021;23:2047-2056.

doi:10.1038/s41436-021-01244-4

4. Leroy JG, Cathey SS, Friez MJ. GNPTAB-Related Disorders. In: Adam MP,

Feldman J, Mirzaa GM, et al., eds. GeneReviews®. Seattle, WA: University of

Washington; 1993–2025. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1828/

5. Miller RD. Miller’s Anesthesia. 8th ed. Philadelphia, PA: Elsevier/Saunders; 2015.

6. Oussoren E, van Eerd D, Murphy E, et al. Mucolipidosis Type III: A Series of Adult

Patients. J Inherit Metab Dis. 2018;41:839-848. doi:10.1007/s10545-018-0186-z