Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients.
To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA).



73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology.



Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed.



Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients.
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Giorgia
G
Querin
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Cinzia
C
Bertolin
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Elisa
E
Da Re
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Marco
M
Volpe
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Gabriella
G
Zara
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Elena
E
Pegoraro
Department of Medicine, Centre for Human Reproduction Pathology, University of Padova, Padova, Italy.
Nicola
N
Caretta
Department of Medicine, Centre for Human Reproduction Pathology, University of Padova, Padova, Italy.
Carlo
C
Foresta
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy.
Maria
M
Silvano
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy.
Domenico
D
Corrado
Department of Oncological and Surgical Sciences, Urology Clinic, University of Padova, Padova, Italy.
Massimo
M
Iafrate
Department of Oncological and Surgical Sciences, Urology Clinic, University of Padova, Padova, Italy.
Lorenzo
L
Angelini
Department of Medical and Surgical Sciences, University of Padova, Padova, Italy.
Leonardo
L
Sartori
Dulbecco Telethon Institute Lab of Neurodegenerative Diseases, Centre for Integrative Biology (CIBIO), University of Trento, Trento, Italy.
Maria
M
Pennuto
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Alessandra
A
Gaiani
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Luca
L
Bello
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Claudio
C
Semplicini
Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences-IRCCS Foundation, "C. Besta" Neurological Institute, Milan, Italy.
Davide
D
Pareyson
Departments of Neurology and Laboratory of Neuroscience, and Pathophysiology and Transplantation, IRCCS Istituto Auxologico Italiano, "Dino Ferrari" Centre, Universita' degli Studi di Milano, Milan, Italy.
Vincenzo
V
Silani
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Mario
M
Ermani
Department of Medicine, Centre for Human Reproduction Pathology, University of Padova, Padova, Italy.
Alberto
A
Ferlin
Department of Neurosciences, Neuromuscular Center, University of Padova, Padova, Italy.
Gianni
G
Sorarù
D000328:Adult; D000368:Aged; D013734:Androgen-Insensitivity Syndrome / Q000150:complications; D001786:Blood Glucose / Q000378:metabolism; D015519:Bone Density; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000097:blood; D006801:Humans; D007558:Italy; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D014570:Urologic Diseases / Q000150:complications
D001786:Blood Glucose; D008055:Lipids; D003402:Creatine Kinase