• Test code: 06189
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Multiple Sulfatase Deficiency Test

Test description

The Invitae Multiple Sulfatase Deficiency test analyzes the SUMF1 gene, which is associated with multiple sulfatase deficiency (MSD). This test is useful for the diagnosis of patients in whom MSD is suspected due to clinical symptoms or biochemical findings.

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Primary panel (1 gene)
Add-on Mucolipidosis and Mucopolysaccharidosis Genes (15 genes)

The phenotypic and/or biochemical features of MSD can overlap with those observed in the mucopolysaccharidoses (MPSs) or mucolipidoses. Given the similarities between these conditions, analyzing the genes associated with the MPSs or the mucolipidoses may be appropriate. These genes can be included at no additional charge.


  • multiple sulfatase deficiency (MSD)
    • neonatal, late-infantile and juvenile subtypes

Multiple sulfatase deficiency (MSD) is a rare metabolic disorder, characterized by deficient activity of all cellular sulfatase enzymes. Affected individuals display combined clinical features from several individual sulfatase deficiencies, including metachromatic leukodystrophy, the mucopolysaccharidoses (MPSs) and X-linked ichthyosis. MSD has a broad phenotypic spectrum and three primary subtypes have been described, based on age of onset and severity: neonatal, infantile and juvenile.

The neonatal type is the most severe, with an onset of symptoms in the first few months of life. Affected individuals exhibit a wide range of clinical manifestations including leukodystrophy, psychomotor delay, neurodegeneration, ichthyosis, dysmorphic/coarse facial features, organomegaly, skeletal anomalies, corneal clouding, hydrocephalus, heart malformations, seizures, hypotonia, respiratory distress, hearing loss, retinitis pigmentosa, ataxia and growth retardation. This form is rapidly progressive, and individuals rarely survive beyond the first year of life.

The late-infantile type is the most common type, and may be further classified as either severe or mild. Onset of symptoms is usually between 1 and 2 years of age. Early cognitive development may be normal, but affected individuals go on to experience psychomotor regression. They also exhibit many of the clinical features observed in the neonatal form. Progression is variable and individuals may survive to late adolescence

The juvenile type is the rarest form of MSD. Early cognitive development is normal, but individuals develop psychomotor regression in mid-to-late childhood. Clinical symptoms are attenuated and progression is slower; individuals may survive to early adulthood.

Individuals with MSD have deficiency of multiple sulfatases, and elevated levels of urinary mucopolysaccharides and sulfatides.

SUMF1 is the only gene known to cause MSD. Due to the small number of individuals in which pathogenic variants in the SUMF1 gene have been identified, an accurate value for detection rate is not available.

MSD is inherited in an autosomal recessive manner.

MSD is a rare condition with less than 50 reported cases to date.

Any individual with deficient activity of multiple sulfatases, elevation of urinary mucopolysaccharides and sulfatides, or a suspected diagnosis of MSD based on clinical presentation, should be tested. Clinical signs that may indicate testing include psychomotor delay and regression, ichthyosis, coarse facial features, organomegaly and skeletal anomalies.

  1. Sabourdy, F, et al. Natural disease history and characterisation of SUMF1 molecular defects in ten unrelated patients with multiple sulfatase deficiency. Orphanet J Rare Dis. 2015; 10:31. PMID: 25885655
  2. Dierks, T, et al. Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme. Cell. 2003; 113(4):435-44. PMID: 12757705
  3. Eto, Y, et al. Pathochemistry, pathogenesis and enzyme replacement in multiple-sulfatase deficiency. Enzyme. 1987; 38(1-4):273-9. PMID: 2894304
  4. Nur, BG, et al. Neonatal multiple sulfatase deficiency with a novel mutation and review of the literature. Turk. J. Pediatr. 2014; 56(4):418-22. PMID: 25818962
  5. Burch, M, et al. Multiple sulphatase deficiency presenting at birth. Clin. Genet. 1986; 30(5):409-15. PMID: 3100114
  6. Garavelli, L, et al. Multiple sulfatase deficiency with neonatal manifestation. Ital J Pediatr. 2014; 40:86. PMID: 25516103
  7. Cosma, MP, et al. Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency. Hum. Mutat. 2004; 23(6):576-81. PMID: 15146462
  8. Schlotawa, L, et al. SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency. Eur. J. Hum. Genet. 2011; 19(3):253-61. PMID: 21224894
  9. Blanco-Aguirre, ME, et al. Unusual clinical presentation in two cases of multiple sulfatase deficiency. Pediatr Dermatol. 2001; 18(5):388-92. PMID: 11737681
  10. Schlotawa, L, et al. Rapid degradation of an active formylglycine generating enzyme variant leads to a late infantile severe form of multiple sulfatase deficiency. Eur. J. Hum. Genet. 2013; 21(9):1020-3. PMID: 23321616

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ARSB NM_000046.3
GALNS NM_000512.4
GLB1 NM_000404.2
GNPTAB NM_024312.4
GNPTG NM_032520.4
GNS NM_002076.3
GUSB NM_000181.3
HGSNAT NM_152419.2
HYAL1 NM_153281.1
IDS* NM_000202.6
IDUA NM_000203.4
MCOLN1 NM_020533.2
NAGLU NM_000263.3
NEU1 NM_000434.3
SGSH NM_000199.3
SUMF1 NM_182760.3

IDS: Detection of complex rearrangements not offered (PMID: 7633410, 20301451).