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Test ID: SUMFZ Multiple Sulfatase Deficiency, Full Gene Analysis, Varies

Reporting Name

SUMF1 Gene, Full Gene Analysis

Useful For

Confirmation of multiple sulfatase deficiency for patients with clinical features


Identification of SUMF1 mutation to allow for genetic testing in family members

Clinical Information

Multiple sulfatase deficiency (MSD) is a rare autosomal recessive lysosomal storage disorder (LSD) caused by mutations in the sulfatase-modifying factor 1 (SUMF1) gene. SUMF1 encodes for a formylglycine-generating enzyme (FGE) that performs a critical posttranslational modification of the catalytic residue necessary for activation of all human sulfatases.


MSD is often confused for a single sulfatase deficiency because it is characterized by deficiency of all known sulfatases, which results in tissue accumulation of sulfatides, sulfated glycoaminoglycans, sphingolipids, and steroid sulfates. Indeed, the clinical phenotype encompasses symptoms of every single sulfatase deficiency, including metachromatic leukodystrophy (MLD), the mucopolysaccharidoses, X-linked ichthyosis, and chondrodysplasia punctata type I. Age of onset and clinical severity are variable and correspond with the level of residual FGE enzyme activity. A severe neonatal form of MSD closely overlaps the clinical presentation of the mucopolysaccharidoses but it is often fatal within 1 year. Late-infantile MSD (onset 0-2 years) accounts for most cases and is characterized by a clinical presentation similar to MLD. Patients show progressive cognitive and motor impairment as well as skeletal changes. More rarely, MSD presents in late childhood (juvenile-onset) with more mild symptoms and slower progression. Patients with late-infantile or juvenile-onset MSD may have less severe sulfatase deficiency.


Patients with a clinical suspicion of MLD, a mucopolysaccharidosis, X-linked ichthyosis, or chondrodysplasia should be investigated for possible FGE deficiency. Urine sulfatide analysis is the recommended first tier biochemical test (CTSA / Ceramide Trihexoside/Sulfatide Accumulation in Urine Sediment, Urine). If positive, iduronate sulfatase and arylsulfatase A and B enzyme levels should be assayed and are typically decreased in patients with MSD.


While enzyme replacement therapy has been used to treat a subset of single LSD, its effectiveness is not well established for patients with MSD. Therefore, confirmation or exclusion of a diagnosis of MSD has important implications for patient management as well as prognosis.


All detected alterations will be evaluated according to the American College of Medical Genetics and Genomics (AMCG) recommendations.(1) Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes No
CRYOB Cryopreserve for Biochem Studies No No

Testing Algorithm

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.


See Lysosomal Storage Disorders Diagnostic Algorithm, Part 2 in Special Instructions.

Report Available

14 to 20 days

Day(s) Performed


Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Dierks T, Schlotawa L, Frese MA, et al: Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease-Lysosomal storage disorders caused by defects of non-lysosomal proteins. Biochim Biophys Acta 2009 Apr;1793(4):710-725

3. Schlotawa L, Ennemann EC, Radhakrishnan K, et al: SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency. Eur J Hum Genet 2011 Mar;19(3):253-261

Method Name

Polymerase Chain Reaction (PCR) Amplification/DNA Sequencing

Specimen Type


Shipping Instructions

Specimen preferred to arrive within 96 hours of draw.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.


Submit only 1 of the following specimens:



Specimen Type: Whole blood


Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated


Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 flask or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours


Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient



Specimen Type: Blood spot

Supplies: Card - Blood Spot Collection (Filter Paper) (T493)


Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper or Blood Spot Collection Card (T493)

Specimen Volume: 2 to 5 blood spots on collection card

Collection Instructions:

1. An alternative blood collection option for a patient >1 year of age is finger stick.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. For collection instructions, see Blood Spot Collection Instructions in Special Instructions.

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.

Specimen Minimum Volume

Blood: 1 mL
Blood Spots: 5 punches, 3-mm diameter

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reference Values

An interpretive report will be provided.

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81479-Unlisted molecular pathology procedure code


Additional tests:

Fibroblast Culture for Genetic Testing

88233-Tissue culture, skin, or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SUMFZ SUMF1 Gene, Full Gene Analysis 89997-1


Result ID Test Result Name Result LOINC Value
54027 Result Summary 50397-9
54028 Result 89997-1
54029 Interpretation 69047-9
54030 Additional Information 48767-8
54031 Specimen 31208-2
54032 Source 31208-2
54033 Released By 18771-6


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions