LAUSR

Dear Editor-in-Chief, A 7-year-old boy presented with a 2-month subtle onset, progressive lower limb weakness with marked difficulty in getting up from the ground. Creatine kinase (CK) level at presentation was 10,000 U/L. No previous infection was reported, and family history was apparently negative for neuromuscular disorders. Neurological exam revealed proximal weakness of all limbs (Medical Research Council [MRC] grade 4, more pronounced at the level of iliopsoas muscles, MRC grade 3) and need for one-hand support to get up from the ground. Multiplex Ligation-Dependent Probe Amplification (MLPA) analysis of Duchenne Muscular Dystrophy (DMD) gene showed no deletion or duplication. Therefore, the patient underwent muscle biopsy (left biceps brachii), which showed a dystrophic pattern with numerous necrotizing and rare regenerating fibers (Fig. 1). In immunohistochemistry analyses, dystrophin and beta-sarcoglycan binding alterations were observed in rare fibers, but western blot analyses highlighted dystrophin, alpha-dystroglycan, calpain-3, dysferlin, and αto δ-sarcoglycans normal molecular weights and amounts. Fukutin-related protein and acid alphaglucosidase genetic investigation also resulted normal. Limbgirdle muscular dystrophy (LGMD) next generation sequencing (NGS) panel did not reveal any known pathogenic mutations. Lower limb muscle magnetic resonance imaging (MRI) showed relative hypotrophy of proximal muscles (i.e., gluteus maximus, thigh adductors, and posterior compartment of thigh) with only mild fibro-adipose substitution but without significant signs of edema (Fig. 2). Echocardiography was normal. During the next 4 months, while work-up results were pending, no therapy was administered. However, the patient complained of rapidly progressive fatigue, weight reduction with mild swallowing dysfunction, difficulty in climbing stairs, and loss of running ability. Simultaneously, the patient developed dermatologicmanifestations characterized by small bald patches of alopecia on the scalp, self-limiting recurring roughening, and cracking of hand fingertips and erythematous papular lesions on ears and extensor surface of elbows and knees (Fig. 1). Four months after the first assessment, neurological examination evidenced four limb muscles weakness (MRC grade between 3 and 4) and diffuse loss of muscular tone involving axial muscles of trunk and head, along with complete Gowers’ sign. Spirometry showed restrictive ventilatory defect of moderate severity (FVC 65%, FEV1 76%, FEV1/FVC 100% of predicted). The patient scored 18/34 at the North Star Ambulatory Assessment (NSAA) and reached 375 m at the 6 Minutes Walking Test (6MWT). CK level was only slightly reduced (8501 U/L, reference values 38-247). Re-evaluation of muscle biopsy highlighted sarcolemmal and sarcoplasmic positivity of anti-major histocompatibility complex (MHC)-I antibodies in some fibers and complement deposition on muscle fiber membranes and capillaries (Fig. 1). Autoimmune serologic screening revealed anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody positivity (268 arbitrary units [AU], reference level < 20), while all the other myositis-specific and myositis-associated autoantibodies tested were negative (i.e., anti-Jo1, anti-PL-7, antiPL-12, anti-Mi-2, anti-SRP-S4, anti-Scl70, anti-Ro/SSA, anti-La/SSB, anti-PM/Scl, and anti-Ku). Four limbs MRI showed the appearance of short-tau inversion-recovery (STIR) signal hyperintensity, particularly at the level of distal leg muscles (i.e., triceps surae, tibial posterior, and peroneus * Daniele Velardo [email protected]