LGMD-D2 TNPO3 related : a wide clinical spectrum Quality of Life and microRNAs study in two families (P6-8.011)

Abstract

<h3>Objective:</h3> To investigate clinical progression, quality of life and circulating microRNAs in patients with LGMD-D2. <h3>Background:</h3> LGMD-D2 is a rare dominant form of limb-girdle muscular dystrophy (LGMD), due to a mutation of TNPO3 gene, that encodes a nuclear protein Transportin-3. Muscle MRI has become a useful tool for diagnosis and to follow the muscle disease evolution in patients with LGMD. We analyse clinical disease evolution, MRI features, MiR-206 expression level in mother and daughter (Family 1) and mother and son (Family 2) with known mutation and a second family with a different mutation. <h3>Design/Methods:</h3> We obtained clinical data, including onset and progression of the disease, from the four patients in two different Italian-Spanish and Hungarian families. The onset of symptoms was characterized by difficulty in walking or climbing stairs, collected by a standard questinnaire, monitored by GSGC score. Muscle MRI was done with 1.5 Tesla Philips apparatus. Individualized Neuromuscular Quality of Life (INQoL) test was used to investigate four patients and two caregivers by telemedicine. Considering the small sample, we used Mann-Whitney U Test for domains of INQoL. <h3>Results:</h3> In 4 years there was substantial disease progress. In family 1 one female case was wheel-chair-bound, in the second family a male child lost ambulation at 14 years. All patients suffered from Covid-19 infection with consequent fatigue and depressive symptoms. This patients have elevated MiR −206 in comparison with healthy controls. Regarding the Quality of Life, we found that there are differences between caregivers and patients in the following domains: body image (p &lt; 0.05) and INQoL Score (p = 0.05). <h3>Conclusions:</h3> The caregiver in both families had a worst evaluation of both physical pain, consequence on Body Image and Social relationship It has been observed that INQoL Score domains (Activities, Independence, Relationships, Emotions and Body image) are worse in this LGMD-D2, than in previous limb-girdle-muscular-dystrophies observations. <b>Disclosure:</b> Miss Rodríguez has nothing to disclose. Valentina Pegoraro has nothing to disclose. Dr. Angelini has nothing to disclose.