An affected male relative [3,16].

Sequence analysis of the entire IDS coding
An affected male relative [3,16]. Sequence analysis of the entire IDS coding region may be necessary if a family-specific mutation is not known. An alternative is first to sequence the exons with the highest prevalence of mutations (e.g. exon IX) or search for recurrent mutations (e.g. p. S333L). Complex rearrangements between IDS and its pseudogene, IDS2, can also be detected by PCR.method for screening, as no heparin is needed and very little blood is required. Dry blood spots are stable for several days at room temperature so transportation of samples is easy [15], and this may extend testing to areas some distance from diagnostic centres, which are not widely available. Documentation of normal enzyme activity of at least one other sulfatase is critical, as low levels of I2S activity are also characteristic of multiple sulfatase deficiency [11]. Finally, molecular genetic testing of IDS to confirm the diagnosis may be useful in male patients with an unusual phenotype PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/23410069 or in whom the results of I2S testing are inconclusive [16]. Molecular genetic testing of IDS is also important for genetic counselling, especially if there is no known family history of MPS II. Once the disease-causing mutation has been identified, a detailed pedigree analysis should be carried out to identify family members who may be carriers of a disease-causing mutation or at risk of the disease, and genetic counselling should be offered to all family members. Prenatal diagnosis and pre-implantation genetic diagnosis can be useful for identifying affected embryos inAssessing disease severity The advent 2-Bromo-4-fluoro-5-methylbenzoic acid of an effective treatment for MPS II has highlighted the need for a standardised method for monitoring the progression of patients with this disease and their response to therapy. There is currently no standardised severity scoring system for MPS II. Biomarkers such as urinary GAGs and heparin cofactor IIthrombin complex [26] PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/4155310 have been proposed, but neither has been found to be a specific marker of disease severity in patients with MPS II [2,27]. Standard functional tests, such as the Pediatric Evaluation of Disability Inventory (PEDI) and a test developed by the Pediatric Orthopedic Society of North America (POSNA) [28,29], may be applicable to patients with MPS II, but this requires confirmation in a relevant population [30]. The validation of a scoring system for such a rare disease as MPS II represents a significant challenge. In the absence of a suitable severity scoring system for MPS II, it is recommended that patients are monitored closely and undergo a comprehensive physical, biochemical, and behavioural evaluation following diagnosis and at least every 6-12 months thereafter (CO). More frequent assessment may be necessary in patients in whom signs and symptoms are progressing rapidly. Where possible, this should take place at a centre with experienceScarpa et al. Orphanet Journal of Rare Diseases 2011, 6:72 http://www.ojrd.com/content/6/1/Page 4 ofPatient with suspected MPS II(Early) clinical signsNoCheck for alternative diagnosisYes Check urinary GAGsDermatan sulfate + heparan sulfate increased Yes MPS II blood enzyme testingNo Key = Start/finish = Next testing step = Decision pointIduronate-2-sulfatase tert-Butyl 2,2-difluoro-3-(methacryloyloxy)pentanoate low Yes Analyse second sulfataseNoOther MPS? Other LSD?Second sulfatase deficiency If molecular gene analysis available NoYesMultiple sulfatase deficiencyIf molecular gene analysis unavailableMolecular analysis of the IDS geneSecond blood enzyme test (e.g. l.