A novel patient presenting late-onset Polyglucosan Body myopathy due to GYG1 mutations: a case report and review of the literature

Elenco Abstract

Nicola Molitierno

A novel patient presenting late-onset Polyglucosan Body myopathy due to GYG1 mutations: a case report and review of the literature

Autori

NICOLA MOLITIERNO (DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MILAN, MILAN, ITALY – SPECIALIZZANDO IN NEUROLOGIA)
DANIELE VELARDO (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY – NEUROLOGIA)
ELENA ABATI (DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MILAN, MILAN, ITALY; 3) IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY – NEUROLOGIA)
SARA ANTOGNOZZI (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY – BIOLOGIA)
MICHELA RIPOLONE (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY – BIOLOGIA)
SIMONA ZANOTTI (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY – BIOLOGIA)
LAURA NAPOLI (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY – BIOLOGIA)
PATRIZIA CISCATO (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY – TECNICO DI LABORATORIO)
MONICA SCIACCO (IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY – NEUROLOGIA)
GIACOMO PIETRO COMI (DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MI-LAN, MILAN, ITALY; 3) IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY – NEUROLOGIA)
STEFANIA PAOLA CORTI (DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MI-LAN, MILAN, ITALY; 2) IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROMUSCULAR AND RARE DISEASE UNIT, MILAN, ITALY – NEUROLOGIA)
DARIO RONCHI (DINO FERRARI CENTER, DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION, UNIVERSITY OF MI-LAN, MILAN, ITALY; IRCCS FONDAZIONE CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, NEUROLOGY UNIT, MILAN, ITALY – BIOLOGIA)

Presentatore

NICOLA MOLITIERNO

Modalità

Poster Session

Abstract

“Polyglucosan bodies (PBs) are deposits of amylopectin-like polysaccharides, detected in muscles of patients affected with glycogenoses-like branching enzyme and phosphofructokinase deficiencies. Pathogenic variants with an autosomal recessive inheritance in GBE1, RBCK1 and GYG1, encoding for glycogenyn-1, have been previously associated with a skeletal PBs myopathy. So far, only few cases with mutations in GYG1 have been reported. GYG1-mutated patients are characterized by variable age at onset (from childhood to 7th decade), mainly proximal weakness, normal creatine kinases levels and myopathic electromyography.
We discuss the clinical, histological, and molecular findings in a novel Italian patient presenting with PBs myopathy.
Our patient is a 79-year-old woman with subacute onset of diffuse soreness, weakness in the upper limbs and diffuse muscle atrophy without cardiac or respiratory involvement. Electromyography showed myopathic features.
Muscle biopsy revealed several type I muscle fibers containing intensely PAS-positive, diastase-resistant vacuoles of variable dimension. Ultrastructural analysis showed vacuoles with granular-fibrillar storage material localized in subsarcolemmal and intermyofibrillar areas, small amounts of free glycogen and jagged Z-line appearance of some sarcomeres. These findings were consistent with polyglucosan body disease.
Clinical exome sequencing revealed two heterozygous variants in GYG1: c.143+3G>C and c.487delG. The variants were rare and classified as Pathogenic according the ACMG criteria. Each variant had been previously found in homozygosis in patients with type 2 PBs myopathy.
Our findings provide clinical and molecular characterization of a novel case of GYG1‐related PBs myopathy and highlight the histological clues leading to the diagnosis of this rare clinical phenotype.”