Persistent asymptomatic or mild symptomatic hyperCKemia due to mutations in ANO5: the mildest end of the anoctaminopathies spectrum

Fecha de publicación: 01/09/2020 Fecha Ahead of Print: 01/05/2020

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

Panades-de Oliveira, L
Bermejo-Guerrero, L
de la Hoz, CPD
Montenegro, DC
Lain, AH
Dominguez-Gonzalez, C

Grupos

Patología Neuromuscular y Ataxias

Investigador Principal

Teresa Sevilla Mantecón

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.

Datos de la publicación

ISSN/ISSNe:: 0340-5354, 1432-1459
Tipo:: Article
Páginas:: 2546-2555
DOI:: 10.1007/s00415-020-09872-7
Factor de Impacto:: 1,541 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Panades-de Oliveira, L:: Hosp Univ 12 Octubre, Dept Neurol, Avda Cordoba S-N, Madrid 28041, Spain
Bermejo-Guerrero, L:: Hosp Univ 12 Octubre, Dept Neurol, Avda Cordoba S-N, Madrid 28041, Spain
de la Hoz, CPD:: Hosp Univ 12 Octubre, Dept Neurol, Avda Cordoba S-N, Madrid 28041, Spain

Hosp Univ 12 Octubre, Dept Neurol, Neuromuscular Disorders Unit, Madrid, Spain
Montenegro, DC:: Hosp Univ 12 Octubre, Dept Neuropathol, Madrid, Spain
Lain, AH:: Hosp Univ 12 Octubre, Dept Neuropathol, Madrid, Spain
Marti, P:: Hosp Univ & Politecn La Fe, Dept Neurol, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Neuromuscular Reference Ctr ERN EURO NMD, Valencia, Spain

Instituto de Investigación. Hosp Univ & Politecn La Fe, IIS La Fe, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Neuromuscular Reference Ctr ERN EURO NMD, Valencia, Spain
Muelas, N:: Hosp Univ & Politecn La Fe, Dept Neurol, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Neuromuscular Reference Ctr ERN EURO NMD, Valencia, Spain

Instituto de Investigación. Hosp Univ & Politecn La Fe, IIS La Fe, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Neuromuscular Reference Ctr ERN EURO NMD, Valencia, Spain
VILCHEZ, JJ:: Hosp Univ & Politecn La Fe, Dept Neurol, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Neuromuscular Reference Ctr ERN EURO NMD, Valencia, Spain

Instituto de Investigación. Hosp Univ & Politecn La Fe, IIS La Fe, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Neuromuscular Reference Ctr ERN EURO NMD, Valencia, Spain
Dominguez-Gonzalez, C:: Hosp Univ 12 Octubre, Dept Neurol, Avda Cordoba S-N, Madrid 28041, Spain

Hosp Univ 12 Octubre, Dept Neurol, Neuromuscular Disorders Unit, Madrid, Spain

Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain

Hosp 12 Octubre, Res Inst Imas12, Madrid, Spain