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arylsulfatase B

Biochemistry/GeneticsMusculoskeletalCardiovascularOphthalmologicHepaticConnective tissue

Summary

Arylsulfatase B (ARSB, N-acetylgalactosamine-4-sulfatase) is a lysosomal enzyme required for the stepwise degradation of glycosaminoglycans (GAGs), specifically dermatan sulfate and chondroitin-4-sulfate. Deficiency causes Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome), an autosomal recessive lysosomal storage disease. Unlike other MPS disorders, intelligence is typically normal.

Detail

Arylsulfatase B removes sulfate groups from N-acetylgalactosamine-4-sulfate residues within dermatan sulfate and chondroitin-4-sulfate, allowing further lysosomal degradation of these glycosaminoglycans. Deficiency of this enzyme results in accumulation of dermatan sulfate within lysosomes of multiple tissues, leading to Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome), inherited in an autosomal recessive pattern due to mutations in the ARSB gene on chromosome 5q13-14.

Clinical features resemble other MPS disorders (coarse facial features, corneal clouding, hepatosplenomegaly, joint stiffness, short stature, skeletal dysplasia/dysostosis multiplex, cardiac valve disease, and hearing loss), but a key distinguishing feature is normal intelligence, since CNS involvement is typically spared (unlike MPS I Hurler or MPS II Hunter). Diagnosis is confirmed by demonstrating elevated urinary dermatan sulfate and decreased arylsulfatase B enzyme activity in leukocytes or fibroblasts.

Treatment involves enzyme replacement therapy with recombinant human arylsulfatase B (galsulfase), which can improve mobility, endurance, and organ size, though it does not reverse skeletal abnormalities already present. Hematopoietic stem cell transplantation has also been used in some cases.

Board relevance: Know to distinguish MPS VI from MPS I (Hurler, due to α-L-iduronidase deficiency) and MPS II (Hunter, due to iduronate-2-sulfatase deficiency, X-linked). MPS VI is unique among the severe MPS disorders for normal cognitive development, making it a classic 'gotcha' on exams testing lysosomal storage disease differentiation.

Sources

  • First Aid for the USMLE Step 1
  • Harper's Illustrated Biochemistry
  • OMIM - Mucopolysaccharidosis Type VI
  • Nelson Textbook of Pediatrics

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