Oxycephaly in Mucolipidosis Type 2 (I-Cell Disease) in a Child: Management Issues in a Rare Case, with Review of Literature

Abstract

Introduction

I-cell disease is rare autosomal recessive lysosomal storage disease which is characterized by accumulation of innumerable intracytoplasmatic inclusions in connective tissue cells. It has multisystemic involvement and often leads to a fatal outcome by early childhood. Craniosynostosis can be present in many cases of I-cell disease and can be even the presenting complaint of the patient. This case report emphasizes the importance of multi-departmental collaboration, extensive preoperative workup, and technical nuances in intraoperative and postoperative management of the child.

Case Presentation

We present a case of a 3-year-old child with mucolipidosis type 2 (I-cell disease) with multisutural craniosynostosis managed with fronto-orbital advancement and anterior cranial vault reconstruction. The patient was undertaken for Operative procedure electively with support from neuroanesthesia and ENT (ear, nose, and throat) teams. The patient could not be intubated despite repeated attempts from the neuroanesthesia team owing to complicated oropharyngeal anatomy. So, decision was taken to tracheostomize the patient by the ENT team. After tracheostomy, the patient underwent fronto-orbital advancement and anterior two–third cranial vault remodeling. There was significant improvement in cosmesis of the patient along with cranial vault expansion. However, in the postoperative period, the child developed ARDS (acute respiratory distress syndrome) and wound infection, for which he received intravenous antibiotics and tracheostomy support. The child was discharged after 2 months of hospitalization under stable conditions.

Conclusion

I-cell disease is an autosomal recessive fatal lysosomal storage disorder, with multiple organ system involvement. Craniosynostosis with I-cell disease can also be managed surgically, after judicious evaluation of risks and benefits involved with active involvement of the caretakers.

Keywords

oxycephaly - mucolipidosis - I-cell disease - craniosynostosis

Introduction

I-cell disease (ICD) is rare autosomal recessive lysosomal storage disease which is characterized by accumulation of innumerable intracytoplasmatic inclusions in connective tissue cells. It has multisystemic involvement and often leads to a fatal outcome by early childhood. We hereby report a case of 3-year-old female child with ICD who presented with multisutural craniosynostosis and was managed with fronto-orbital advancement and cranial vault reconstruction. This case report emphasizes the importance of multi-departmental collaboration, extensive preoperative workup, and technical nuances in intraoperative and postoperative management of the child.

Case Presentation

A 3-year-old female child presented with gradually progressive abnormal shape of head, abnormal facial features, and protrusion of both eyes since birth. On examination of head and face, the patient had tower-shaped skull (oxycephaly), temporal bulging, proptosis, depressed nasal bridge, gingival hypertrophy, with normally placed ears ([Fig. 1a]). Head circumference was 40 cm (<2 standard deviation, suggestive of microcephaly) with cephalic index of 90% (suggestive of brachycephaly).

Fig. 1 (A) Preoperative photograph of a child with I-cell disease showing abnormal head shape, coarse facial features, depressed nasal bridge, short stubby fingers, and proptosis. (B) Chest X-ray showing right tracheal deviation and cardiomegaly. (C) X-ray hand showing proximal tapering of metacarpals, which is a characteristic finding in I-cell disease. (D) Preoperative NCCT head with 3D reconstruction showing fused sagittal, coronal, and lambdoid suture with oxycephaly. MRI brain (E) with MRV (F) showing no abnormality in brain parenchyma with persistent falcine and occipital sinus with right transverse sinus atrophic. 3D, three-dimensional; MRI, magnetic resonance imaging; MRV, magnetic resonance venography; NCCT, noncontrast computed tomography.

On fundus examination, there was no evidence of any papilledema; bilateral disc was pale which was suggestive of early optic atrophy.

On neurodevelopmental evaluation and neuropsychological evaluation, there was significantly hampered gross motor, fine motor, and language and cognitive milestones.

On ENT (ear, nose, and throat) evaluation, there was a depressed nasal bridge. Bilateral vocal cords were mobile.

On general physical examination, the patient had shot stubby fingers ([Fig. 1c]) and toes with inability to move both elbow and knee joints because of ankylosis. The patient also had chest deformity in the form of pectus carinatum.

The patient was thoroughly investigated. Patient X-ray chest was suggestive of tracheal deviation to the right side with cardiomegaly ([Fig. 1b]) and HRCT (high-resolution computed tomography) chest was suggestive of pectus carinatum chest-wall deformity with linear atelectasis of the right upper lobe with small airway disease.

Preoperative polysomnographic study was suggestive of severe upper airway obstruction.

The patient underwent NCCT (noncontrast computed tomography) head with three-dimensional construction ([Fig. 1d]), which was suggestive of multisutural craniosynostosis. The patient also underwent MRI (magnetic resonance imaging) brain with MRI venogram ([Fig. 1e, f]), which revealed normal brain parenchyma with persistent falcine and occipital sinus with atrophic right transverse sinus.

Two-dimensional echo was done, which was suggestive of a small atrial septal defect with left to right shunt, low-to-moderate mitral regurgitation, and mild aortic regurgitation with normal ejection fraction.

On the basis of genetic workup, the patient was diagnosed as a case of mucolipidosis type 2. Patient's enzyme activity of plasma aryl-α-sulphatase-A was 926.19 nmol/h/mg (normal 34–180) and of plasma hexo-saminidase-A was 1,513.04 nmol/h/mg (normal 94–300).

Both enzyme levels were significantly raised, which was suggestive of mucolipidosis type 2.

On the basis of all investigations, diagnosis of multisutural craniosynostosis with mucolipidosis type 2 with multisystemic involvement (cardiac, lung, and joints) was made.

Patient's parents were counselled about prognosis of the child and was undertaken for surgery after proper explanation of risks and benefits involved to the parents.

The patient was undertaken for surgery in view of features of gross development delay and neurocognitive decline and raised ICP (intracranial pressure) features.

The patient was undertaken for elective OT with support from neuroanesthesia and ENT team. The patient could not be intubated despite repeated attempts from the neuroanesthesia team owing to complicated oropharyngeal anatomy. So, a decision was taken to tracheostomize the patient by the ENT team ([Fig. 2a, b]).

Fig. 2 Preoperative photograph of a child showing tracheostomy, abnormal head shape from lateral (A) and anterior (B) views. Postoperative photograph following fronto-orbital advancement and anterior two-third cranial vault reconstruction. Superior view (C) and lateral view (D). Postoperative NCCT head with 3D reconstruction showing reconstructed calvarium with increased intracranial volume, barrel staved frontal and parietal bone, and fronto-orbital advancement. (E) Anterior view and (F) left lateral view. 3D, three-dimensional; NCCT, noncontrast computed tomography.

After tracheostomy, the patient underwent fronto-orbital advancement and anterior two–third cranial vault remodeling.

Immediate postoperative images are given in [Fig. 2(c, d)]. Postoperative 3D CT images are depicted in [Fig. 2(e, f)]. There was significant improvement in cosmesis of the patient along with cranial vault expansion.

But in the postoperative period, the child developed ARDS (acute respiratory distress syndrome) and wound infection, for which he received intravenous antibiotics and tracheostomy support. The child was discharged after 2 months of hospitalization under stable conditions.

Discussion

I-cell disease (mucolipidosis type 2) is a very rare disorder which is specifically an autosomal recessive lysosomal storage disease.[1] “I-cell disease” is named because connective tissue cells contain innumerable intracytoplasmic inclusions in this disorder.[2]

It is caused by deficiency of N-acetylglucosamine-1-phosphotransferase. This enzyme is responsible for tagging lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome.[3] Normally, GlcNAc-1-phosphotransferase is responsible for catalyzing the transfer of GlcNAc-1-phosphate to the mannose residues on lysosomal enzymes present in the cis-Golgi network. Then N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase removes GlcNAc from lysosomal enzymes and exposes the M6P residues in the trans-Golgi network. Trans Golgi network then targets the enzymes to lysosomes by M6P receptors. In ICD, enzyme deficiency causes the hypersecretion of lysosomal enzymes out of cells. This results in a shortage of multiple lysosomal enzymes within lysosomes.

As a result, lysosomes get accumulated with cholesterol, phospholipids, glycosaminoglycans, and other substrates.[4]

This disease has clinical onset at birth and leads to a fatal outcome by early childhood. It is associated with restricted postnatal growth, joint contractures, skin thickening, coarsening of facial features, gingival hypertrophy, psychomotor retardation, organomegaly (hepatosplenomegaly), generalized hypotonia, developmental delay, and dysostosis multiplex.[5]

Our patient also had the same features along with multisutural craniosynostosis.

Craniosynostosis can be present in many cases of ICD and can be even the presenting complaint of the patient.[6]

In 2014, Chittem et al[6] reported a rare case of ICD presenting with craniosynostosis. In their case report, an 11-month-old child presented with abnormal head shape, developmental delay, and bent bones, and on genetic analysis ICD was confirmed. After explaining the prognosis of ICD, parents denied surgery in their case.

Because of involvement of multiple organ systems, ICD is associated with a severely restricted life expectancy, with most of the patients dying before first decade of life. Management is aimed at symptom palliation since no curative treatment is available.[7]

In our case also, patient's relatives were counselled about the disease, its future prospects for the child, the treatment options available, palliative nature of treatment, benefits of undergoing surgical treatment for craniosynostosis and risks involved in surgery, and postoperative complications. After their informed consent, the patient was taken for surgery.

The patient was undertaken for operative intervention for craniosynostosis since the patient had severe microcephaly and signs of raised ICP, with dural outpouching through cranium, causing frontal bumps evident on preoperative images.

Since such patients have poor prognosis despite treatment, whether to take such patients for surgery or not is a matter of ethical and moral debate. Decisions should always be taken judiciously respecting the wishes and emotions of the caretakers.

Patients with ICD have significant respiratory dysfunction owing to lysosome failure to clear debris, which is a major cause of morbidity and mortality. Respiratory dysfunction may occur because of bulky airway anatomy, extensive pulmonary fibrosis, persistent hemosiderosis, pulmonary airway excrescences, obstructive sleep apnea, tracheal deviation, tracheal narrowing, repeated episodes of pneumonia, and ARDS.[8]

In our case also, the patient had significant sleep apnea on polysomnography study, tracheal deviation, right pulmonary fibrosis, difficult intubation, requirement of preoperative tracheostomy, postoperative ARDS, pneumonia requiring intravenous antibiotics, and ventilator support for 1.5 months.

In conclusion, ICD is an autosomal recessive fatal lysosomal storage disorder, with multiple organ system involvement. Craniosynostosis with ICD can also be managed surgically, after judicious evaluation of risks and benefits involved with active involvement of the caretakers.

Conflict of Interest

None declared.

Authors' Contribution

S.G., T.M., and D.G. contributed to the composition of the manuscript. D.G., S.G., T.M., and K.P. were the operating surgeons. G.P. was the chief neuroanesthesiologist during operation. R.L. were the chief pediatrician involved in preoperative assessment and postoperative care of the patient. All authors reviewed the manuscript.

• References

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Publication History

Article published online:
02 April 2025