Clinical and genetic features of a cohort of patients with myoadenilate deaminase deficiency: a new mutation

Elenco Abstract

CLAUDIA ALBERTI

Clinical and genetic features of a cohort of patients with myoadenilate deaminase deficiency: a new mutation

Autori

CLAUDIA ALBERTI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY. – NEUROLOGY)
SABRINA LUCCHIARI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY. – )
MARTINA RIMOLDI (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
FRANCESCO FORTUNATO (NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
DANIELE VELARDO (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY. – )
LAURA NAPOLI (NEUROMUSCULAR AND RARE DISEASES UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
MAURIZIO MOGGIO (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY.; NEUROMUSCULAR AND RARE DISEASES UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
NEREO BRESOLIN (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY.NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
GIACOMO PIETRO COMI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY.NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
STEFANIA CORTI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY.;NEUROMUSCULAR AND RARE DISEASES UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )
ELENA ABATI (DEPARTMENT OF PATHOPHYSIOLOGY AND TRANSPLANTATION (DEPT), DINO FERRARI CENTRE, NEUROSCIENCE SECTION, UNIVERSITY OF MILAN, MILAN, ITALY.;NEUROLOGY UNIT, FONDAZIONE IRCCS CA’ GRANDA OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY – )

Presentatore

CLAUDIA ALBERTI

Modalità

Poster Session

Abstract

Introduction: Myoadenylate deaminase deficiency is the predominant metabolic disorder affecting skeletal muscles in the Caucasian population, involving approximately 2% of individuals. While the majority of those with the deficiency remain asymptomatic, some experience symptoms induced by exercise, suggesting a link between reduced enzyme activity and muscle function.
Methods: We conducted a cross-sectional analysis on 8 patients harboring mutations in AMPD1 and exhibiting a biochemical deficiency of myoadenylate deaminase (MAD) at histopathological analyses.
Results: Evaluated patients demonstrated a variable age of onset and a broad phenotypic spectrum, with most presenting exercise-induced myalgia and proximal weakness. Routine blood tests showed no significant abnormalities, except for persistent elevation in serum creatine kinase (CK). DNA analysis revealed the nonsense mutation c.34C>T (p.Q45*) in all patients, except for one with a novel compound heterozygous mutations p.Arg494Ser and p.Met511Val. These mutations located at a highly conserved position were predicted to be pathogenic by in silico tools. In comparison to other patients, the carrier of the novel mutation exhibited an earlier onset within the first months of life and a more pronounced elevation of serum creatine kinase (CK) levels, which then progressed to proximal, limb-girdle type myopathy.
Discussion: In conclusion, our work expands the genetic spectrum of MAD deficiency, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with AMPD1 mutations. These findings support a pathogenic role for MAD deficiency, influencing not only energy metabolism but also the development of skeletal muscle.