PB1975 CHRONIC FATIGUE, ANAEMIA AND MUSCULOSKELETAL AFFECTATION IN GAUCHER DISEASE

Abstract

Background:Chronic fatigue is the most prevalent symptom in type 1 Gaucher disease(GD1) (79%) and persists in spite of prolonged therapy which usually achieves the general goals (24.5%). It is mainly attributed to hypermetabolism, myopathy or increase in plasma cytokine concentration. There are several factors such as anaemia, pain, depression, anxiety, sleep disturbances, emotional distress, activity level or medication side effects that could be involved. Bone abnormalities are present in over 70% of the patients and peripheral neuropathy in about 11% of them, which contributes to the disabling and debilitating complications. Our hypothesis is that other factors including muscle‐tendinous weakness could have influence in the development of fatigue.Aims:The aim of the study is to evaluate for first time the study the fiber structure in muscle‐tendinous unit and compromised elasticity usefulness of real‐time tissue Strain‐Elastography in the assessment of the Achilles tendon fibres in GD patients with or without bone marrow infiltration by MRI and their influence in the chronic fatigue.Methods:We have study the fibrillar structure (rigidity) of muscletendinous tissues in Achilles tendon applying a noninvasive technique based on Strain‐Elastography (Hitachi system EUB‐8500, L54 M transducer, frequency 6‐13 MHz) and combined this exam with bone marrow burden study using Spanish‐MRI score and calcaneus ultrasound densitometry for bone mineral density evaluation. We have selected 21 GD1 and 2 type 3 patients (mean age: 46.9 y, 18‐65, 12 females) with chronic fatigue, on enzymatic replacement therapy (mean time 12.0 years, 2‐25). Non history of diabetes, endocrine diseases or concomitant steroid therapy were present. Control group: 20 healthy subjects matched by gender and age. Correlation study with blood cell counts, plasma biomarkers, genotype, concomitant diseases and SF36 quality of life scale (QoL) were performed. A longitudinal and axial scans was performed in each Achilles tendon in proximal, middle and distal third.Results:Mean Hb (g/dL) in females: 13.3 (12.2‐14.1), in males: 14.8 (13.0‐17.3), advanced bone disease 10 patients (43.5%), S‐MRI (5.1 points; 0‐18), Osteopenia 8 patients (34.7%), T‐score (mean ‐0.76, ‐2.68‐1.51), Z‐score (mean ‐0.53, ‐2.43‐1.45), genotype N370S/L444P (47.8%), N370S/other (34.7%), L444P/other (17.4%), Ferritin: 310.7 (30‐2000), Chitotriosidase (1,813 nmol/mL/h 50‐6,575). CCL18/PARC (256.3 ng/mL 55‐553), Lyso‐Gb1 (32.9 ng/mL 0‐144). All patientes have a normal tendinous structure (mode B). Intratendinuous alteration in Strain‐elastography (S‐ELA) grade 2‐3 was found in 14 /23 (61%) patients and bilateral in 9/23 (21.7%). There are not correlation between S‐ELA grade to other variables. QoL evaluation showed a low score in physical and emotional roles and general health and high in pain. There are a significant correlation between the degree of tendon hardness and the low score on the QoL scales, (p = 0.0035).Summary/Conclusion:In Achilles tendon Strain‐elastography is a sensitive method to detect subclinical disfunction of muscle‐tendinous that could contribute to fatigue symptom in GD. Intratendinuous alteration is one independent variable in GD patients. The cause of this disfunction probably has a mechanical origen and can be a risk factor for the development of skeletal complications. A project based on physical activity has been developed to Increase the functional strength of the lower limbs achieve greater stability, power and improvement in physical activities, as well as the reduction of fatigue.