No 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.

ABSTRACT. Objectives. Children with generalized hypermobility of the joints and musculoskeletal complaints frequently visit pediatric clinics, but many show no currently known collagen or other possibly related diseases. Whether the symptoms are confined to the musculoskeletal system is unknown. We assessed whether such children have detectable differences in laxity of connective tissue present in organ systems other than joints. We also assessed whether children with generalized joint hypermobility and musculoskeletal complaints have more profound systemic changes in connective tissue of various organ systems as compared with children with generalized joint hypermobility without musculoskeletal complaints.Methods. Anthropometrics, range of joint motion, muscle strength, skin extensibility, blood pressure, quantitative ultrasound measurements of bone, and degradation products of collagen were studied in 15 prepubertal children with generalized joint hypermobility and musculoskeletal complaints and compared with a population-based reference group of 95 nonsymptomatic prepubertal children. Symptomatic hypermobile children were also compared with children of the population-based reference group who had asymptomatic hypermobility of the joints (n ‫؍‬ 16).Results. Children with symptomatic generalized joint hypermobility had significantly higher skin extensibility (5.6 mm/15 kPa, 95% confidence interval [CI]: 4.0 -7.1), lower quantitative ultrasound measurements (speed of sound: ؊26.8 m/s; 95% CI: ؊41.1 to ؊12.6) in bone, and lower systolic and diastolic blood pressure (؊8.0 mmHg, 95% CI: ؊13.3 to ؊2.8; and ؊6.0 mmHg, 95% CI: ؊10.0 to ؊2.2, respectively) as compared with the total reference group. Also, they had significantly lower excretion of urinary hydroxylysylpyridinoline crosslinks (mean difference: ؊51.3 mol/mmol; 95% CI: ؊92.2 to ؊10.4) as well as lysylpyridinoline cross-links (؊18.7 mol/mmol; 95% CI: ؊36.9 to ؊0.5). Age, gender, body weight, height, and particularly cross-links excretion did not explain group differences in clinical and bone characteristics. After adjustment for age, gender, body weight, and height, children with symptomatic generalized joint hypermobility (n ‫؍‬ 15) had significantly higher total range of joint motion (117.8 degrees; 95% CI: 77.7-158.0), skin extensibility (3.5 mm/15 kPa; 95% CI: 1.6 -5.3), lower quantitative ultrasound measurements in bone (speed of sound: ؊27.9 m/s; 95% CI: ؊48.4 to ؊7.5), borderline lower diastolic blood pressure (؊4.9 mmHg; 95% CI: ؊10.7-0.9), and significantly higher degradation products in urine (hydroxyproline/creatinine: 21.2 mol/ mmol; 95% CI: 2.3-40.1) as compared with asymptomatic hypermobile children of the total reference group (n ‫؍‬ 16). After adjustment for possible confounders, children with generalized joint hypermobility without musculoskeletal complaints had a significantly higher total range of joint motion and more profound skin extensibility, as compared with the reference group (n ‫؍‬ 79).Conclusions. Clinically manifested symptoms i...