Hurler syndrome

Suruthiga1*, Poornima B2, Dhariniya S3, Ruby Ravichandran4

1Staff Nurse, Pediatric General Ward, Maa Kauvery, Trichy, Tamil Nadu

2Incharge, Pediatric General Ward, Maa Kauvery, Trichy, Tamil Nadu

3Nursing Educator, Maa Kauvery, Trichy, Tamil Nadu

4Senior Deputy Nursing Superintendent, Maa Kauvery, Trichy, Tamil Nadu

*Correspondence

Abstract

Hurler syndrome, also known as mucopolysaccharidosis type I–Hurler (MPS I-H), is a rare autosomal recessive lysosomal storage disorder caused by deficiency or absence of the enzyme alpha-L-iduronidase (IDUA). The enzyme deficiency results in progressive accumulation of glycosaminoglycans, particularly dermatan sulfate and heparan sulfate, in multiple tissues and organs. Consequently, affected children develop characteristic facial features, skeletal abnormalities, hepatosplenomegaly, cardiac and respiratory involvement, joint stiffness, corneal clouding, hearing impairment, and progressive neurological deterioration. This case represents a child with clinical features suggestive of Hurler syndrome, subsequently evaluated through biochemical, enzymatic, and molecular investigations. The diagnosis of MPS I is established by demonstrating deficient IDUA enzyme activity together with increased glycosaminoglycan excretion and/or identification of pathogenic variants in the IDUA gene. Management requires a multidisciplinary approach involving metabolic specialists, pediatricians, neurologists, cardiologists, respiratory specialists, physiotherapists, and transplant teams. Disease-modifying treatment includes enzyme replacement therapy with Laronidase and, in appropriately selected children with severe MPS I, early hematopoietic stem cell transplantation (HSCT). Early diagnosis and treatment are important because HSCT is most effective when performed before significant neurological deterioration occurs.

Key words: Hurler syndrome; Mucopolysaccharidosis

 

Introduction

Hurler syndrome is the severe form of mucopolysaccharidosis type I, a group of inherited lysosomal storage disorders caused by impaired degradation of glycosaminoglycans. MPS I result from pathogenic variants in the IDUA gene, leading to deficient alpha-L-iduronidase activity. Progressive accumulation of glycosaminoglycans produces multisystem disease involving the central nervous system, skeleton, joints, heart, respiratory tract, liver, spleen, eyes, and ears. Hurler syndrome is generally present in early childhood and is characterized by progressive developmental impairment together with somatic manifestations. Common clinical findings include coarse facial appearance, macrocephaly, hepatosplenomegaly, umbilical or inguinal hernia, joint stiffness, skeletal dysplasia, corneal clouding, hearing impairment, airway obstruction, cardiac valve disease, and developmental delay.

Because the disease is progressive and multisystem, early recognition is essential. Definitive diagnosis requires biochemical and enzymatic confirmation, with molecular genetic testing providing additional confirmation and information regarding the underlying IDUA variants. Current management focuses on disease-modifying treatment together with comprehensive supportive care and surveillance for complications.

Case Presentation

The child was brought for evaluation because of progressive developmental and physical abnormalities suggestive of an underlying storage disorder. The history was notable for gradually increasing coarseness of facial features, abdominal distension, joint stiffness, skeletal abnormalities, and developmental delay. The child also had features suggestive of upper-airway and respiratory involvement, which are recognized manifestations of MPS I. There was no history suggestive of an acquired cause for the progressive multisystem abnormalities. A detailed developmental history was obtained to assess attainment and regression of developmental milestones. Family history was also explored because MPS I is inherited in an autosomal recessive pattern, and genetic counselling and carrier evaluation are important for affected families.

Clinical Findings

On clinical examination, the child demonstrated characteristic phenotypic features consistent with Hurler syndrome. The facial appearance was coarse, with macrocephaly and other typical dysmorphic features. Abdominal examination suggested hepatosplenomegaly, while musculoskeletal examination revealed joint stiffness and skeletal abnormalities. The child was assessed for developmental and neurological status because severe MPS I can cause progressive central nervous system involvement. Cardiovascular assessment was performed to identify possible valvular disease or myocardial involvement, while respiratory assessment focused on airway obstruction, recurrent respiratory symptoms, and sleep-related breathing abnormalities. Ophthalmological and auditory assessments were also considered because corneal clouding and hearing impairment are common manifestations. MPS I guidelines emphasize comprehensive baseline evaluation of neurological, ophthalmological, auditory, cardiac, respiratory, gastrointestinal, and musculoskeletal systems.

Investigations and results

Investigations were directed toward confirming MPS I and determining the extent of systemic involvement. Urinary glycosaminoglycan analysis was performed as an initial biochemical investigation, with elevated glycosaminoglycan levels supporting the possibility of mucopolysaccharidosis. Confirmation was obtained through measurement of alpha-L-iduronidase activity in an appropriate biological specimen, demonstrating deficient enzyme activity. Molecular genetic testing of the IDUA gene can identify pathogenic variants on both alleles and provides definitive genetic confirmation. Additional investigations were undertaken to assess disease burden and complications, including echocardiography for cardiac involvement, hearing assessment, ophthalmological examination, skeletal radiographs, respiratory evaluation, neurological assessment, developmental assessment, and abdominal ultrasonography for hepatosplenomegaly. These investigations are important for establishing baseline and planning individualized treatment and long-term follow-up.

Diagnosis

Based on the characteristic clinical phenotype and confirmatory biochemical, enzymatic, and genetic investigations, the child was diagnosed with Hurler syndrome (Mucopolysaccharidosis type I-H). The diagnosis is supported by deficient alpha-L-iduronidase activity in combination with elevated glycosaminoglycans and/or identification of biallelic pathogenic variants in the IDUA gene. The severe Hurler phenotype is distinguished from attenuated forms of MPS I by its early onset, rapid progression, and significant central nervous system involvement.

Management

Management was planned through a multidisciplinary team. Enzyme replacement therapy with recombinant human alpha-L-iduronidase, laronidase, may be used to reduce systemic glycosaminoglycan storage and improve several somatic manifestations. However, Laronidase does not adequately cross the blood-brain barrier and therefore cannot be relied upon to prevent neurological deterioration in severe Hurler syndrome. For appropriately selected children with severe MPS I, hematopoietic stem cell transplantation is the major disease-modifying treatment because donor-derived cells can provide the deficient enzyme and may preserve neurological function when transplantation is performed early. Current recommendations emphasize early transplantation, particularly before significant cognitive impairment develops. Supportive management included monitoring and treatment of respiratory problems, cardiac disease, hearing and visual impairment, skeletal abnormalities, joint stiffness, developmental difficulties, and nutritional concerns. Physiotherapy, occupational therapy, speech and developmental support were incorporated according to the child’s needs. Particular caution was required during any surgical or anesthetic procedure because airway and cervical spine abnormalities can increase anesthetic risk in children with MPS.

Outcome

The child’s outcome was assessed through regular multidisciplinary follow-up. Response to disease-modifying treatment was monitored through clinical examination, developmental assessment, urinary glycosaminoglycan measurements where appropriate, cardiac and respiratory evaluation, and assessment of skeletal, ophthalmological, and auditory manifestations. Treatment cannot completely reverse established storage-related abnormalities; therefore, the primary goals are to slow disease progression, preserve neurological function, reduce systemic complications, and improve quality of life. Early HSCT in severe MPS I can improve survival and modify the progression of neurological disease, although some skeletal, ocular, and cardiac manifestations may continue to require long-term management.

 

Discharge

Following stabilization and completion of the initial evaluation and treatment plan, the child was discharged with a detailed multidisciplinary follow-up plan. The caregivers were educated regarding the chronic and progressive nature of Hurler syndrome, the importance of treatment adherence, scheduled enzyme replacement therapy when prescribed, and follow-up investigations. Parents were advised to monitor respiratory difficulty, recurrent respiratory infections, feeding problems, changes in activity, developmental concerns, seizures, sleep disturbances, cardiac symptoms, and other signs of clinical deterioration. Genetic counselling was recommended for the family to explain the autosomal recessive inheritance pattern, carrier testing, and reproductive options. Long-term follow-up with the metabolic, pediatric, cardiac, respiratory, neurological, ophthalmological, audiological, and rehabilitation teams were emphasized.

Conclusion

Hurler syndrome is a rare but serious inherited lysosomal storage disorder characterized by progressive accumulation of glycosaminoglycans and multisystem involvement. Early recognition of characteristic clinical features followed by urinary glycosaminoglycan testing, enzyme assay, and molecular genetic confirmation is essential for establishing the diagnosis. Treatment requires a coordinated multidisciplinary approach. Laronidase enzyme replacement therapy provides important systemic benefits, while early hematopoietic stem cell transplantation remains the principal disease-modifying treatment for appropriately selected children with severe MPS I, particularly when undertaken before significant neurological impairment. Comprehensive nursing care, regular monitoring, rehabilitation, family education, genetic counselling, and lifelong follow-up are essential components of care. Early diagnosis and timely intervention provide the best opportunity to preserve neurological function, reduce complications, and improve the child’s overall quality of life.

References

  1. Muenzer, J., Wraith, J. E., Clarke, L. A., & International Consensus Panel on Management and Treatment of MPS I. (2009). Mucopolysaccharidosis I: Management and treatment guidelines. Pediatrics, 123(1), 19–29.
  2. De Ru, M. H., Boelens, J. J., Das, A. M., Jones, S. A., van der Lee, J. H., Mahlaoui, N., … Jones, S. A. (2011). Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: Results of a European consensus procedure. Orphanet Journal of Rare Diseases, 6, 55.

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