Clinical presentation, diagnosis and treatment of acid sphingomyelinase deficiency in children

Abstract:

Disease caused by acid sphingomyelinase deficiency (ASMD) is a progressive, autosomal recessive inherited lysosomal storage disease, caused by pathogenic variants of the SMPD1 gene. Decreased sphingomyelinase activity leads to accumulation of sphingomyelin in hepatocytes, spleen, lungs, brain cells, lymph nodes and other cells of monocytemacrophage lineage. Clinical presentation is variable, depending primarily on the type of mutations of the SMPD1 gene, but also on disease phase and numerous other factors. In children, it is characterized in various combinations by primarily hepatosplenomegaly and her consequences, interstitial lung disease, growth retardation and in neurological forms of the disease by hypotonia, later cerebellar symptoms and signs, extrapiramidal symptoms, mental regression, epilepsy, psychiatric and other disorders. The visceral signs and symptoms are etiologically treatable by enzyme replacement therapy, but the outcome significantly depends on the phase of disease at the time of the treatment onset. Therefore, specific tests for revealing the cause should be performed as soon as possible in children with mentioned unexplained signs and symptoms.

Key words:
acid sphingomyelinase deficiency; enzyme replacement therapy; children; diagnosis; Niemann-Pick disease