Musculoskeletal manifestations of lysosomal storage disorders

Abstract

Lysosomal storage disorders (LSDs), a heterogeneous group of inborn metabolic disorders, are far more common than most doctors presume. Although patients with a severe LSD subtype are often readily diagnosed, the more attenuated subtypes are frequently missed or diagnosis is significantly delayed. The presenting manifestations often involve the bones and/or joints and therefore these patients are frequently under specialist care by (paediatric) rheumatologists, receiving inadequate treatment. Since effective disease-specific treatments, including enzyme replacement therapy and stem cell transplantation, have become available for certain LSDs and timely initiation of these treatments is necessary to prevent the development of severe, disabling and irreversible manifestations, early diagnosis has become essential. The challenge is to raise awareness for better recognition of the presenting signs and symptoms of LSDs by all doctors who may encounter these patients, including rheumatologists.

Pitfalls in Diagnosing Neuraminidase Deficiency: Psychosomatics and Normal Sialic Acid Excretion

“…This traditional diagnostic test should thus remain part of screening panels for storage disorders. Avascular osteonecrosis is well described in a variety of LSDs, including Gaucher's disease (Aldenhoven et al 2009) and to a lesser extent Fabry disease (Lien and Lai 2005;Sacre et al 2010) and Niemann-Pick type B (Wasserstein et al 2013). Thus far, it has not been considered a clinical sign of neuraminidase deficiency.…”

Therapies for the bone in mucopolysaccharidoses

“…However, skeletal disease, including genu valgum, thoracolumbar kyphosis and hip dysplasia, still develops after HSCT and consequently this treatment provides a limited impact to ADL because of pain and loss of ambulation. Skeletal deformity is less responsive to HSCT compared with favorable effects related to other important clinical outcome parameters including CNS involvement [25,[87][88][89][90][91][92][93][94]. The skeletal abnormalities lead to a need for orthopedic corrective surgeries.…”

Lysosomale Speicherkrankheiten

“…Betrachtet man alle zusammen als Gruppe, findet sich eine Prävalenz von einer Erkrankung auf 7100 bis 7700 Lebendgeborene. Die tatsächliche Häufigkeit könnte jedoch durchaus noch höher liegen, da milde Verlaufsformen leicht initial übersehen werden können [5].…”