Fabry cardiomyopathy: missing links from genotype to phenotype

Fuller, Maria; Mehta, Atul

doi:10.1136/heartjnl-2019-316143

Cited by 5 publications

(1 citation statement)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Associating particular genetic variants with lysosomal disease is challenging and a notable example is provided with Fabry disease where a single base change at the same residue reportedly results in a spectrum of severity from asymptomatic -monosymptomatic -classical Fabry disease. 84 Biomarkers A biomarker is defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses . Amplification-refractory mutation system (ARMS) for the identification of the N370S molecular variant in a patient with Gaucher disease.…”

Section: Molecular Geneticsmentioning

confidence: 99%

Laboratory Diagnosis of Lysosomal Diseases: Newborn Screening to Treatment

Fuller

2020

CBR

View full text Add to dashboard Cite

The goal of screening programs for inborn errors of metabolism (IEM) is early detection and timely intervention to significantly reduce morbidity, mortality and associated disabilities. Phenylketonuria exemplifies their success as neonates are identified at birth and then promptly treated allowing normal neurological development. Lysosomal diseases comprise about 50 IEM arising from a deficiency in a protein required for proper lysosomal function. Typically, these defects are in lysosomal enzymes with the concomitant accumulation of the enzyme's substrate as the cardinal feature. None of the lysosomal diseases are screened at birth in Australia and in the absence of a family history, traditional laboratory diagnosis of the majority, involves demonstrating a deficiency of the requisite enzyme. Diagnostic confusion can arise from interpretation of the degree of residual enzyme activity causative of disease and is impractical when the disorder is not due to an enzyme deficiency per se. Advances in mass spectrometry technologies has enabled simultaneous measurement of the enzymes' substrates and their metabolites which facilitates the efficiency of diagnosis. Employing urine chemistry as a reflection of multisystemic disease, individual lysosomal diseases can be identified by a characteristic substrate pattern complicit with the enzyme deficiency. Determination of lipids in plasma allows the diagnosis of a further class of lysosomal disorders, the sphingolipids. The ideal goal would be to measure biomarkers for each specific lysosomal disorder in the one mass spectrometry-based platform to achieve a diagnosis. Confirmation of the diagnosis is usually by identifying pathogenic variants in the underlying gene, and although molecular genetic technologies can provide the initial diagnosis, the biochemistry will remain important for interpreting molecular variants of uncertain significance.

show abstract

Section: Molecular Geneticsmentioning

confidence: 99%