Genetic and Metabolic Diseases: To Split or to Lump?

Background Neurodevelopmental disorders, hypotonia, microcephaly or macrocephaly, poor growth and distinctive facial traits are some of the most common reasons to refer a child to an expert consultant. But which expert? A priori response might not be always predictable. Clinical experience teaches that it is not unusual to come across a metabolic diagnosis in a patient suspected of a genetic condition and vice versa. Still, although phenotypically convergent, genetic and metabolic disorders strongly diverge on therapeutic availability. In such an entangled scenario, new sequencing technologies may bring to light further uncertainties, detecting variants that often need a clinical confirm to be interpreted. Methods. In order to explore clinical convergence among metabolic and genetic disorders we present a cases’ collection of patients wrongly referred to metabolic disorder clinic or to medical genetic service in a third level Center in the North of Italy. Results. Data gained from this retrospective review demonstrate the striking importance of multi-disciplinary management of complex pediatric cases. Conclusions. In Hub Hospitals and in rare diseases’ Centers, it appears mandatory to promote a side by side collaboration embracing pediatricians, clinical geneticists and laboratory in order to take an all-around point of view of undiagnosed patients. What falls out of our competence might fall out of our view as well.