MPS VII - Extending the classical phenotype.

Area of Science:

• Biochemistry
• Genetics
• Rare Diseases

Background:

• Mucopolysaccharidosis VII (MPS VII), or Sly syndrome, stems from Beta-glucuronidase (GUSB) deficiency.
• This deficiency impairs glycosaminoglycan (GAG) degradation, leading to lysosomal accumulation and multisystem damage.
• MPS VII exhibits extreme clinical variability, complicating early diagnosis based on symptoms alone.

Observation:

• A 31-year-old male with a history of developmental delay, skeletal deformities, and sensory impairments was diagnosed with MPS VII at age 28.
• The patient's unusual presentation delayed diagnosis, despite multiple specialist consultations.
• Diagnosis was confirmed by GUSB deficiency in leukocytes and elevated urinary GAGs, with genetic sequencing revealing two novel GUSB mutations.

Findings:

• The patient presented with features overlapping severe non-classical MPS VII manifestations.
• Despite the presentation, his metabolic condition remained stable into adulthood.
• Genetic analysis identified compound heterozygous mutations in the GUSB gene: c.526C>T p.(Leu176Phe) and c.1820G>C p.(Gly607Ala).

Implications:

• This case expands the known phenotypic spectrum of MPS VII.
• It underscores the diagnostic challenges posed by the variable presentation of MPS VII.
• The findings emphasize the importance of considering MPS VII in patients with unexplained multisystemic symptoms, even with atypical features.