Consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency

Disclaimer: This diagnostic guideline is intended as an educational resource and represents the opinions of the authors, and is not representative of recommendations or policy of the American College of Medical Genetics and Genomics (ACMG). The information should be considered a consensus based on expert opinion, as more comprehensive levels of evidence were not available in the literature in all cases. Background: Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, and often fatal lysosomal storage disease. The underlying metabolic defect is deficiency of the enzyme acid sphingomyelinase that results in progressive accumulation of sphingomyelin in target tissues. ASMD manifests…

Methods for a prompt and reliable laboratory diagnosis of Pompe disease : report from an international consensus meeting

Pompe disease is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). It presents at any age, with variable rates of progression ranging from a rapidly progressive course, often fatal by one-year of age, to a more slowly, but nevertheless relentlessly progressive course, resulting in significant morbidity and premature mortality. In infants, early initiation of enzyme replacement therapy is needed to gain the maximum therapeutic benefit, underscoring the need for early diagnosis. Several new methods for measuring GAA activity have been developed. The Pompe Disease Diagnostic Working Group met to review data gener…

Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes-possibility for newborn screening.

Pompe disease is a rare, autosomal-recessive disorder which results from a defect in the lysosomal enzyme acid alpha-glucosidase (GAA). The onset of this disease is highly variable, with infantile types being the most severe. Traditionally, lymphocytes, fibroblasts or muscle biopsies were necessary for enzyme activity measurement, because these materials do not express maltase-glucoamylase (MGA) that interferes with the assay. Recently, acarbose was found to inhibit MGA activity selectively, so that dried blood became accessible for GAA assessment.To evaluate the diagnostic efficacy of GAA measurement in dried blood specimens (DBSs) in comparison with lymphocytes. If DBSs provided reliable …

Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD)

Abstract Background Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, results from mutations in SMPD1, the gene encoding acid sphingomyelinase (ASM). As a result, sphingomyelin accumulates in multiple organs including spleen, liver, lung, bone marrow, lymph nodes, and in the most severe form, in the CNS and peripheral nerves. Clinical manifestations range from rapidly progressive and fatal infantile neurovisceral disease, to less rapidly progressing chronic neurovisceral and visceral forms that are associated with significant morbidity and shorter life span due to respiratory or liver disease. Objectives To provide a contemporary guide of clinical assessments for di…

Consensus recommendation on a diagnostic guideline for acid sphingomyelinase deficiency