When should a rheumatologist consider lysosomal storage diseases as a cause of musculoskeletal symptoms?
There are over 50 lysosomal storage diseases (LSDs). Some presenting in childhood may have musculoskeletal symptoms that are initially misdiagnosed as juvenile idiopathic arthritis. However, patients with attenuated LSD forms may look “normal” and present as a teenager or adult with rheumatic symptoms. The following are a list of LSDs that can occur in a mild or attenuated form (i.e., can present with rheumatic symptoms later in life) and the unusual extraarticular manifestations that should alert a clinician that the LSD that is the cause of the symptoms:
- • Mucopolysaccharidoses (MPS)
- • MPS I-Hurler–Scheie (HS): joint stiffness/contracture, claw-hand deformity, coarse facies, short stature, corneal clouding
- • MPS I-Scheie (S): hip dysplasia, joint stiffness/contracture, coarse facies, heart murmurs, corneal clouding
- • MPS II (Hunter): milder than Hurler–Scheie syndrome, hepatosplenomegaly, short stature, clear corneas
- • MPS IVA and IVB (Morquio syndrome): type IVB is the milder form, pectus carinatum, odontoid hypoplasia with cervical spine instability, kyphoscoliosis, joint laxity, genu valgum, heart murmurs, corneal clouding
- • MPS VI (Maroteaux–Lamy): joint stiffness/contracture, claw-hand deformity, heart murmurs, corneal clouding
- • Gaucher disease, type 1: bone pain, osteonecrosis, hepatosplenomegaly, growth retardation
- • Fabry disease: acroparesthesia, cold/heat intolerance, angiokeratoma, cornea verticillata, paternal history of early-onset renal failure
- • Farber disease: periarticular subcutaneous nodules, painful swollen joints, hepatosplenomegaly, nephropathy, ceramidase deficiency.
