Authors: Juan Manuel Sánchez-Vargas, Lina Johanna Moreno Giraldo
Introduction: Niemann-Pick A and B diseases (NPD), are part of the group of lysosomal storage diseases caused by acid sphingomyelinase (ASM) deficiency, which catalyzes the hydrolysis of sphingomyelin (SM) to ceramide and phosphocholine. As a result, SM and its precursor lipids accumulate in lysosomes in cells of the reticuloendothelial system, leading to loss of the ability to degrade macromolecules, forming intracellular inclusions that are deposited in organs. NPD-A/B are caused by deleterious variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, leading to defective formation of this enzyme and preventing the movement of lipids out of the cells.
Case report: 20-month-old infant with neurodevelopmental delay, malnutrition, dysmorphic facies and hepatosplenomegaly. The initial approach ruled out infectious and lymphoproliferative diseases. A targeted clinical exome was performed which showed two variants of the SMPD1 gene (compound heterozygous), one of pathogenic clinical significance and the other probably pathogenic. In the enzymatic activity, it was found increased biomarker lyso-SM-509 and decreased ASM activity, with which phenotype-genotype correlation with NPD-A/B is performed.
Discussion and Conclusion: With a defined and precise diagnosis it is possible to guide health actions, follow-up guidelines, risk assessment of the inheritance model through an index case in order to find possible carriers, perform a complete genetic counseling, implement and initiate targeted treatments to reduce morbidity and mortality associated with this pathology.