I-Cell Disease (Mucolipidosis II): A Case Series from a Tertiary Paediatric Centre Reviewing the Airway and Respiratory Consequences of the Disease

  • Rachel EdmistonEmail author
  • Stuart Wilkinson
  • Simon Jones
  • Karen Tylee
  • Alexander Broomfield
  • Iain A. Bruce
Research Report
Part of the JIMD Reports book series (JIMD, volume 45)


Background: Inclusion cell disease (I-cell) is a rare autosomal recessive metabolic disease involving multiple organ systems, associated with a severely restricted life expectancy. No curative therapy is currently available, with management aimed at symptom palliation.

Methods: We present a retrospective, single-centre, case series of children referred to a tertiary paediatric metabolic service. The clinical presentation, demographics, genetics and natural history of the condition are investigated.

Results: Five patients with I-cell disease were referred over a 10-year period. All patients were born with dysmorphic features and had a family history of I-cell disease on further exploration. Phenotypic variation was seen within patients with the same genetic profile. Airway problems were common with 100% of the documented sleep oximetry studies suggesting sleep-disordered breathing. Of the two patients who had tracheal intubation anaesthetic difficulties we encountered, one required intraoperative reintubation, and one suffered a failed intubation with subsequent death. All five patients required oxygen therapy with the use of CPAP and BiPAP also seen. Feeding issues were almost universal with four of the five patients requiring nasogastric feeding. Four patients had died in the 10-year period with a mean life expectancy of 36 months. Cause of death for three of the four patients was respiratory failure.

Conclusions: Airway problems, including sleep-disordered breathing, were ubiquitous in this cohort of children. Any intervention requiring a general anaesthetic needs careful multidisciplinary consideration due to significant associated risks and possibly death. Management as a result is generally non-surgical and symptomatic. This case series demonstrates universal involvement of the airway and respiratory systems, an important consideration when selecting meaningful outcomes for future effectiveness studies of novel therapies.


Airway I-cell disease Inclusion cell Mucolipidosis II Respiratory disorders 



Bilevel positive airway pressure


Continuous positive airway pressure




Laryngeal mask airway


Nasogastric tube


Oxygen deprivation index


Obstructive sleep apnoea


Patent ductus arteriosus


Percutaneous endoscopic gastrostomy


Sleep-disordered breathing



Not applicable.


  1. Brouillette RT, Morielli A, Leimanis A, Waters KA, Luciano R, Ducharme FM (2000) Nocturnal pulse oximetry as an abbreviated testing modality for pediatric obstructive sleep apnea. Pediatrics 105:405–412CrossRefGoogle Scholar
  2. Cathy SS, Kudo M, Tiede S, Raas-Rothschild A, Braulke T, McKusick VA (2008) Molecular order in mucolipidosis II and III nomenclature. Am J Med Genet A 146(5):512–513CrossRefGoogle Scholar
  3. Eminoglu F, Yaman A, Kendrili T, Odek C, Ucar T (2016) Mucolipidosis type II (I-cell disease) with pulmonary hypertension and difficult airway. Mol Genet Metab 117(2):S45Google Scholar
  4. Gilbert EF, Dawson G, zu Rhein GM, Opitz KM, Spranger JW (1972) I-cell disease, mucolipidosis II pathological, histochemical ultrastructural and biochemical observations in four cases. Z Kinderheilkd 114:259–292CrossRefGoogle Scholar
  5. Hakim M, Walia H, Krishna S, Tobias J (2017) Anaesthetic management of a 13 years old adolescent with mucolipidosis type II for total hip arthroplasty. J Med Cases 8(7):203–206CrossRefGoogle Scholar
  6. Hanai J, Leroy J, O’Brien JS (1971) Ultrastructure of cultured fibroblasts in I-cell disease. Am J Dis Child 122(1):34–38PubMedGoogle Scholar
  7. Ishak M, Zambrano E, Bazzy-Asaad A, Esquibies A (2012) Unusual pulmonary findings in mucolipidosis II. Pediatr Pulmonol 47(7):719–721CrossRefGoogle Scholar
  8. Leroy G, Cathey S, Friez M (2012) Mucolipidosis II. Gene Reviews.
  9. Lynch SA, Crushell E, Lambert D, Bryne N et al (2018) Catalogue of inherited disorders found among the Irish Traveller population. J Med Genet 55(4):233–239CrossRefGoogle Scholar
  10. Mallen J, Highstein M, Smith L, Cheng J (2015) Airway management considerations in children with I-cell disease. Int J Pediatr Otorhinolaryngol 79(5):760–762CrossRefGoogle Scholar
  11. Mueller T, Honey N, Little L (1983) Mucolipidosis II and III: the genetic relationships between two disorders of lysosomal enzyme biosynthesis. J Clin Invest 72(3):1016–1023CrossRefGoogle Scholar
  12. Peters ME, Arya S, Langer LO, Gilbert EF, Carlson R, Adkins W (1985) Narrow trachea in mucopolysaccharidoses. Pediatr Radiol 15:225–228CrossRefGoogle Scholar
  13. Roth W, Jones S, Beauve B, Dearlove O (2015) Anaesthesia recommendations for patients suffering from: mucolipidosis II and III. Anasthesiol Intensivmed 56(9):636–641Google Scholar
  14. Sheikh S, Madiraju K, Qazi Q, Rao M (1998) Improved morbidity with the use of nasal continuous positive airway pressure in i-cell disease. Pediatr Pulmonol 25:128–129CrossRefGoogle Scholar
  15. Simmons MA, Bruce IA, Penney S, Wraith E, Rothera MP (2005) Otorhinolaryngological manifestations of the mucopolysaccharidoses. Int J Paediatr Otorhinolaryngol 69(5):589–595CrossRefGoogle Scholar
  16. Walker R, Allen D, Rothera M (1997) A fibreoptic intubation technique for children with mucopolysaccharidoses using the laryngeal mask airway. Paediatr Anaesth 7:421–426CrossRefGoogle Scholar
  17. Wiesmann UN, Herschkowitz NN (1981) Mucolipidosis II and III: the clinical pictures and pathogenetic mechanisms. Persp Inherit Metab Dis 4:437–451Google Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Rachel Edmiston
    • 1
    Email author
  • Stuart Wilkinson
    • 2
  • Simon Jones
    • 3
  • Karen Tylee
    • 3
  • Alexander Broomfield
    • 3
  • Iain A. Bruce
    • 1
    • 4
  1. 1.Paediatric ENT DepartmentRoyal Manchester Children’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science CentreManchesterUK
  2. 2.Paediatric Respiratory DepartmentRoyal Manchester Children’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science CentreManchesterUK
  3. 3.Willink Biochemical Genetics UnitManchester Centre for Genomic Medicine, St. Mary’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science CentreManchesterUK
  4. 4.Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK

Personalised recommendations