1. Persistent asymptomatic or mild symptomatic hyperCKemia due to mutations in ANO5: the mildest end of the anoctaminopathies spectrum
- Author
-
Luísa Panadés-de Oliveira, Laura Bermejo-Guerrero, Aurelio Hernández Lain, Nuria Muelas, Juan J. Vílchez, Diana Cantero Montenegro, Cristina Domínguez-González, Carlos Pablo de Fuenmayor-Fernández de la Hoz, and P Martí
- Subjects
Weakness ,medicine.medical_specialty ,Neurology ,Exercise intolerance ,Calf hypertrophy ,Anoctamins ,Asymptomatic ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Muscular Diseases ,Chloride Channels ,Internal medicine ,medicine ,Myocyte ,Humans ,030212 general & internal medicine ,Muscle, Skeletal ,Neuroradiology ,Retrospective Studies ,Muscle biopsy ,medicine.diagnostic_test ,business.industry ,ANO5 gene ,Magnetic resonance imaging ,Asymptomatic hyperCKemia ,Middle Aged ,STIR sequences ,Mutation ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Inflammatory biopsy - Abstract
Background The ANO5 gene encodes for anoctamin-5, a chloride channel involved in muscle cell membrane repair. Recessive mutations in ANO5 are associated with muscular diseases termed anoctaminopathies, which are characterized by proximal or distal weakness, or isolated hyperCKemia. We present the largest series of patients with asymptomatic/paucisymptomatic anoctaminopathy reported so far, highlighting their clinical and radiological characteristics. Methods Twenty subjects were recruited retrospectively from the Neuromuscular Disorders Units database of two national reference centers. All had a confirmed genetic diagnosis (mean age of diagnosis was 48 years) established between 2015 and 2019. Clinical and complementary data were evaluated through clinical records. Results None of the patients complained about weakness or showed abnormal muscular balance. Among paucisymptomatic patients, the main complaints or findings were generalized myalgia, exercise intolerance and calf hypertrophy, occasionally associated with calf pain. All patients showed persistent hyperCKemia, ranging from mild-moderate to severe. Muscle biopsy revealed inflammatory changes in three cases. Muscle magnetic resonance imaging revealed typical signs (preferential involvement of adductor and gastrocnemius muscles) in all but one patient. In two cases, abnormal findings were detectable only in STIR sequences (not in T1). Three patients showed radiological progression despite remaining asymptomatic. Twelve different mutations in ANO5 were detected, of which seven are novel. Conclusions Recessive mutations in ANO5 are a frequent cause of undiagnosed asymptomatic/paucisymptomatic hyperCKemia. Patients with an apparent indolent phenotype may show muscle involvement in complementary tests (muscle biopsy and imaging), which may progress over time. Awareness of anoctaminopathy as the cause of nonspecific muscular complaints or of isolated hyperCKemia is essential to correctly diagnose affected patients.
- Published
- 2020