2025/07/01 by Jean‐Marie Saudubray, Manuel Schiff · 1 voice
Biochemistry, Genetics and Molecular Biology · #Genomics and Rare Diseases #Metabolism and Genetic Disorders #Mitochondrial Function and Pathology
paper · pdf · doi:10.1002/jimd.70063
openalex publication_date 2025/07/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
The concept of IMDs has evolved over a century from rare deficits in amino acid catabolism diagnosed by the accumulation of biochemical markers such as phenylketonuria (PKU) to diseases affecting organelle metabolism, synthesis of complex molecules, and cellular trafficking. Small-molecule accumulation disorders form the major group of treatable IMDs. Do not miss these metabolic emergencies! IMDs currently number over 1800 and include all medical specialties. The specificity of true "molecular internists," metabolic specialists, lies in the in-depth knowledge of metabolic pathways and the understanding of the pathophysiology of the deficits underlying the treatments ("precision medicine"). Neurology is massively impacted, but cerebral metabolism remains largely misunderstood. Genetic analyses are becoming increasingly important for diagnosis but must be complemented by biochemical investigations, which sometimes have greater diagnostic specificity and provide functional information at the phenotype level. Biochemical analyses remain essential for monitoring treatment or even for diagnosis. Finally, contrary to early expectations, newborn screening such as that for phenylketonuria, leading to preventive therapy, could be extended to a significant though limited number of IMDs. Currently, there are numerous initiatives that include genetic screening combined with biochemical testing or that extend screening to lysosomal diseases potentially treatable by enzyme or gene therapy.