Assay of heparan-N-sulfamidase in dried leukocytes impregnated in filter paper: A new tool for the identification of Mucopolisaccharidosis IIIA and potentially other lysosomal disorders

Civallero, Gabriel; Mari, J. De; Camelier, M.; Burin, Maira Graeff; Giugliani, Roberto

doi:10.1016/j.ymgme.2013.02.001

Cited by 7 publications

(6 citation statements)

References 9 publications

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“…The definitive diagnosis is generally obtained by analyzing the enzymatic activity of the different enzymes in blood serum, leukocytes or fibroblasts. Given that some lysosomal enzymes, such as heparan‐ N ‐sulfamidase, cannot be measured in dried blood spots, a new assay involving dried leukocytes impregnated in filter paper has been developed . In general, MPS symptoms develop when residual enzyme activity falls below a threshold of 15%, but in some cases of MPS III residual activity did not exceed 3% .…”

Section: Diagnosismentioning

confidence: 99%

Sanfilippo syndrome: Overall review

Andrade

Aldámiz‐Echevarría

Llarena

et al. 2015

Pediatrics International

104

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Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of the four enzymes involved in the catabolism of glycosaminoglycan heparan sulfate. It is characterized by progressive cognitive decline and severe hyperactivity, with relatively mild somatic features. This review focuses on clinical features, diagnosis, treatment, and follow-up of MPS III, and provides information about supplementary tests and differential diagnosis. Given that few reviews of MPS III have been published, several studies were compiled to establish diagnostic recommendations. Quantitative urinary glycosaminoglycan analysis is strongly recommended, and measurement of disaccharides, heparin cofactor II-thrombin complex and gangliosides is also used. Enzyme activity of the different enzymes in blood serum, leukocytes or fibroblasts, and mutational analysis for SGSH, NAGLU, HGSNAT or GNS genes are required to confirm diagnosis and differentiate four subtypes of MPS III. Although there is no global consensus for treatment, enzyme replacement therapy and gene therapy can provide appropriate results. In this regard, recent publications on treatment and follow-up are discussed.

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Section: Diagnosismentioning

confidence: 99%

Sanfilippo syndrome: Overall review

Andrade

Aldámiz‐Echevarría

Llarena

et al. 2015

Pediatrics International

104

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“…These studies aim to determine total concentration of specific metabolites and to measure specific enzyme activities. 2,3,[7][8][9][10][11][12][13][14][15][16][17][18][22][23][24] Chitotriosidase activity can be used for screening, as it is increased in plasma and DBS in several LSDs. Creatinine and protein determinations are generally performed as parameters to normalize other biochemical assays that refer its results to creatinine or protein concentrations, such as organic acids, GAGs, sialic acid, enzyme assays in tissues or leucocytes, and so on.…”

Section: Spectrophotofluorometric Studiesmentioning

confidence: 99%

“…The use of this type of samples facilitates its transportation from remote areas to specialized centers and could be extended to other metabolite studies, since their effectiveness was truly demonstrated. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] Despite these advances, an important deficiency is still evident. The number of laboratories dedicated to the study of IEM is very limited worldwide, and more laboratories performing IEM screening and diagnosis are required for a more efficient detection and therapy of patients.…”

Section: Introductionmentioning

confidence: 99%

High-Risk Screening and Diagnosis of Inborn Errors of Metabolism

Civallero

Kremer

Giugliani

2018

Journal of Inborn Errors of Metabolism and Screening

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Inborn errors of metabolism (IEM) are a large and heterogeneous group of genetic diseases. In most of these conditions, the presence of variants in specific genes leads to enzyme deficiencies that affect a particular metabolic step. The number of laboratories dedicated to the study of IEM is very limited worldwide, and its multiplication is urgently required for a more effective diagnosis. With the scarcity of specialized centers, the diagnosis of affected individuals comes too late or does not happen at all. Moreover, the biological samples have to travel long distances, compromising its quality and delaying still more the diagnosis. In this work, we suggest a practical guide for a basic biochemical laboratory to get involved in the study of IEM. This proposal was based on already described metabolic tests and involves the need of just a few, simple, and affordable instruments that can give an enormous quantity of information about the possible metabolic defect faced, such as a spectrophotofluorometer and a gas chromatography/mass spectrometry (GC/MS) instrument. The procedures proposed can be customized and adapted to particular needs and situations, which make it especially useful for developing countries.

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“…The assays also require long incubation times. Some lysosomal enzymes such as heparan N-sulphamidase, the enzyme deficient in MPS IIIA, cannot be assayed in this way but can be assayed in material eluted from leukocytes dried on filter paper (Civallero et al 2013b). These limitations on the use of dried blood spots for diagnostic assays can be overcome using two different technologies.…”

Section: Identification Of Mps Sub-type By Analysis Of Non-reducing Ementioning

confidence: 99%

Lysosomal diseases: diagnostic update

Winchester

2014

J of Inher Metab Disea

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Technological developments in newborn and population screening, biomarker discovery for monitoring treatment and rapid high throughput DNA sequencing are having a great impact on the diagnostic procedure for symptomatic patients with lysosomal storage diseases. The use of dried blood spots, initially for newborn screening, has stimulated the introduction of automated, rapid and more sensitive methods for the assay of lysosomal enzymes, including the synthesis of novel substrates. Storage products and secondary metabolites in urine and cells can be identified and measured very accurately and sensitively by high performance liquid chromatography and tandem mass spectrometry. This has enhanced the preliminary metabolite screen for LSDs and facilitated the diagnosis of transport defects. Fast, reliable and affordable high throughput DNA sequencing, such as whole or selected exome sequencing, is helping to make diagnoses in difficult cases, to reveal novel gene defects, to widen the clinical spectrum of diseases and possibly to identify modifying genetic factors. Bioinformatics will be necessary to handle the data generated by these new technologies. Notwithstanding, these technical innovations, accurate and reliable diagnosis will still depend on the knowledge and experience of skilled laboratory staff.

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Assay of heparan-N-sulfamidase in dried leukocytes impregnated in filter paper: A new tool for the identification of Mucopolisaccharidosis IIIA and potentially other lysosomal disorders

Cited by 7 publications

References 9 publications

Sanfilippo syndrome: Overall review

Sanfilippo syndrome: Overall review

High-Risk Screening and Diagnosis of Inborn Errors of Metabolism

Lysosomal diseases: diagnostic update

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