Differential Diagnosis of Mild Form of Mucopolysaccharidosis Type I (Scheie Syndrome) and Juvenile Systemic Scleroderma (Case Study)

Background. Mild forms of mucopolysaccharidosis type I (MPS I), Hurler – Scheie and Scheie syndromes, are characterized by late onset and non-specific symptoms. Particularly, the clinically dominant joint may lead to misdiagnosis of rheumatic disease. Case description. Girl S., at the age of 4 years 8 months, has shown limitation in hands' joints movements. Later at the age of 5 years and 1 month symmetrical polyarthritis with damage of large and small joints of upper and lower limbs with contractures was revealed; antinuclear factor was 1 : 160; and juvenile idiopathic arthritis was diagnosed. Then at the age of 5 years 2 months diagnosis has changed to limited form of juvenile systemic scleroderma due to additional symptoms onset: induration and elasticity decrease of hands, forearms, feet and lower legs skin, restriction of mouth opening, gastrointestinal tract lesions (cardia insufficiency, gastroesophageal reflux). Management with antirheumatic therapy (methylprednisolone, methotrexate) resulted in decreased skin density and increased amplitude of joints movements. Clinical features and disease course forced us to continue the diagnostic search. Enzyme diagnostics was performed: decrease in alpha-iduronidase activity to 0.06 μmol/L (normal range 1.00–25.00 μmol/L) was revealed. Quantitative analysis of glycosaminoglycans (GAG) in urine was performed: total GAG level was 20.0 mg/mmol creatinine (age limit 0.8–24.9 mg/mmol creatinine). One-dimensional GAG electrophoresis has revealed increased heparan sulfate and dermatan sulfate urinary excretion. Direct automatic sequencing of exons 2 and 7 of the IDUA gene revealed pathogenic variant c.208C>T (pGin70Term), from the father, and change in the nucleotide sequence c.878_889dup leading to the replacement of p.Thr293_Tyr2, from mother, in compound heterozygous state. The diagnosis of “MPS I, Sheie syndrome” was established.

Conclusion. Pediatricians and pediatric rheumatologists should include molecular genetic methods in the examination protocols for the timely detection of hereditary diseases, particularly mild forms of MPS I, when conducting differential diagnosis in patients with specific articular changes.

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