Sign in →

Test ID: LSD6 Lysosomal Storage Disorders Newborn Screen, Blood Spot

Useful For

First-tier newborn screen for the lysosomal disorders: Fabry, Gaucher, Krabbe, mucopolysaccharidosis I (MPS-I), Niemann-Pick types A and B, and Pompe (Glycogen storage disorder type II)

Testing Algorithm

First-tier results will be reviewed and second-tier screening performed at clinical biochemical geneticist discretion at no additional charge. This minimizes the false-positive rate and maximizes the positive predictive value of screening for these lysosomal storage disorders.


The following algorithms are available in Special Instructions:

-Newborn Screen Follow-up for Gaucher Disease

-Newborn Screen Follow-up for Infantile Krabbe Disease

-Newborn Screen Follow-up for Mucopolysaccharidosis Type I

-Newborn Screen Follow-up for Niemann Pick Type A and B

-Newborn Screen Follow-up for Pompe Disease


For more information, see the following Newborn Screening ACT Sheets:

-Newborn Screening Act Sheet Fabry Disease: Decreased Alpha-Galactosidase A

-Newborn Screening Act Sheet Gaucher Disease: Decreased Acid Beta-Glucosidase

-Newborn Screening Act Sheet Krabbe Disease: Decreased Galactocerebrosidase

-Newborn Screening Act Sheet Mucopolysaccharidosis Type I: Decreased Alpha-L-Iduronidase

-Newborn Screening Act Sheet Niemann-Pick A/B Disease: Decreased Acid Sphingomyelinase

-Newborn Screening Act Sheet Pompe Disease: Decreased Acid Alpha-Glucosidase

Method Name

Flow Injection Analysis-Tandem Mass Spectrometry (FIA-MS/MS)

Reporting Name

Lysosomal Newborn Screen, BS

Specimen Type

Whole blood

Necessary Information

Birth weight, time of birth, and gestational age are required.

Specimen Required

Patient must be older than 24 hours and less than 1 week of age.


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


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

Acceptable: Ahlstrom 226 filter paper, Munktell filter paper, Whatman Protein Saver 903 Paper, or blood collected in tubes containing ACD, EDTA, or heparin and dried on filter paper

Specimen Volume: 2 blood spots

Collection Instructions:

1. Completely fill at least 2 circles on the filter paper card (approximately 100 microliters blood per circle).

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

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

4. Do not stack wet specimens.

5. Keep specimen dry.

Additional Information:

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

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

Specimen Minimum Volume

1 blood spot

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Refrigerated (preferred) 60 days
  Frozen  60 days
  Ambient  30 days

Clinical Information

Lysosomes are intracellular organelles that contain hydrolytic enzymes that degrade a variety of macromolecules. Lysosomal storage disorders are a diverse group of inherited diseases characterized by the intracellular accumulation of macromolecules due to defects in their transport mechanisms across the lysosomal membrane or due to defective lysosomal enzyme function. The accumulation of these macromolecules leads to cell damage and, eventually, organ dysfunction. More than 40 lysosomal storage disorders have been described with a wide phenotypic spectrum.


Gaucher disease is an autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme, beta-glucosidase. Beta-glucosidase facilitates the lysosomal degradation of glucosylceramide (glucocerebroside) and glucopsychosine (glucosylsphingosine). Gaucher disease is caused by mutations in the GBA gene. There are 3 described types of Gaucher disease with varying clinical presentations and age of onset from a perinatal lethal disorder to an asymptomatic type. Features of all types of Gaucher disease include hepatosplenomegaly and hematological abnormalities.


Treatment is available in the form of enzyme replacement therapy, substrate reduction therapy, and chaperone therapy for types 1 and 3. Currently, only supportive therapy is available for type 2.


 Niemann-Pick types A and B are caused by a deficiency of sphingomyelinase due to mutations in the SMPD1 gene. The result is extensive storage of sphingomyelin and cholesterol in the liver, spleen, lungs, and, to a lesser degree, brain. Classification of type A versus type B is based on the age of onset as well as the severity of symptoms. Niemann-Pick type A disease is more severe and characterized by early onset with feeding problems, dystrophy, persistent jaundice, cherry red maculae, development of hepatosplenomegaly, neurological deterioration, deafness, and blindness, leading to death  by age 3. Niemann-Pick type B disease is limited to visceral symptoms with survival into adulthood. Some patients have been described with intermediary phenotypes. Characteristic of the disease are large lipid-laden foam cells on bone marrow biopsy. The combined prevalence of the two types is estimated to be 1 in 250,000. Treatment is supportive, although there are clinical trials in place.


Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA; acid maltase) due to mutations in the GAA gene. The estimated incidence is 1 in 40,000 live births. In Pompe disease, glycogen that is taken up by lysosomes during physiologic cell turnover accumulates, causing lysosomal swelling, cell damage, and, eventually, organ dysfunction. The clinical presentation of Pompe disease ranges from a rapidly progressive infantile variant, which is uniformly lethal if untreated, to a more slowly progressive late-onset variant. All disease variants are eventually associated with progressive muscle weakness and respiratory insufficiency. Cardiomyopathy is associated almost exclusively with the infantile form. Enzyme replacement therapy is available for all variants and should be started as soon as possible for patients with the infantile variant and at the first signs of muscle weakness in the later onset variants.


Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive disorder caused by mutations in the GALC gene resulting in a deficiency of galactocerebrosidase (GALC, galactosylceramide beta-galactosidase). Galactosylceramide (as with sulfated galactosylceramide) is a lipid component of myelin. The absence of GALC results in globular, distended, multinucleated bodies in the basal ganglia, pontine nuclei, and cerebral white matter. There is severe demyelination throughout the brain with progressive cerebral degenerative disease affecting primarily the white matter. Patients with this early infantile onset variant of Krabbe disease (<1 in 250,000 live births) die within 2 years. Late infantile-onset Krabbe disease manifests between 6 and 12 months of life and leads to death within a few years as well. Juvenile and adult onset variants present later in life, progress more slowly and, based on newborn screening experience in New York, appear to be more common than the earlier onset variants. Of note, Krabbe disease variants, including pseudodeficiency, may not be discriminated by enzyme activity measurement. Molecular genetic analysis of the GALC gene may provide information on expected age of first symptoms. Psychosine has been shown to be elevated in patients with clinical signs and symptoms of disease and therefore, may be a useful biomarker for the presence of disease or disease progression. The only available therapy is hematopoietic stem cell transplantation that is best performed prior to the onset of clinical symptoms. Early infantile Krabbe disease must therefore be considered a critical, time sensitive newborn screening condition.


Fabry disease, caused by mutations in the GLA gene, is an X-linked recessive disorder with an incidence of approximately 1 in 50,000 males. Symptoms result from a deficiency of the enzyme alpha-galactosidase A (GLA; ceramide trihexosidase). Reduced GLA activity results in accumulation of glycosphingolipids in the lysosomes of both peripheral and visceral tissues. Severity and onset of symptoms are dependent on the residual GLA activity. Males with less than 1% GLA activity have the classic form of Fabry disease. Symptoms can appear in childhood or adolescence and usually include acroparesthesias (pain crises), multiple angiokeratomas, reduced or absent sweating, and corneal opacity. Renal insufficiency, leading to end-stage renal disease and cardiac and cerebrovascular disease, generally occur in middle age. Males with more than 1% GLA activity may present with a variant form of Fabry disease. The renal variant generally has onset of symptoms in the third decade. The most prominent feature in this form is renal insufficiency and, ultimately, end-stage renal disease. Individuals with the renal variant may or may not share other symptoms with the classic form of Fabry disease. Individuals with the cardiac variant are often asymptomatic until they present with cardiac findings such as cardiomyopathy or mitral insufficiency in the fourth decade. The cardiac variant is not associated with renal failure. Females who are carriers of Fabry disease can have clinical presentations ranging from asymptomatic to severely affected. Pseudodeficiency alleles may also be detected by newborn screening. Treatment with enzyme replacement therapy (ERT) is available for both males and females with Fabry disease.


Mucopolysaccharidosis I (MPS-I) is an autosomal recessive disorder caused by a reduced or absent activity of the alpha-L-iduronidase (IDUA) enzyme. MPS-I is caused by mutations in the IDUA gene and has an estimated incidence of approximately 1 in 100,000 live births. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.

Reference Values

Not applicable


An interpretive report is provided.


The quantitative measurements of informative metabolites and related ratios and their bioinformatic evaluation using the Collaborative Laboratory Integrated Reports (CLIR) system support the initial interpretation of the complete profile and may suggest the need to perform the measurement of more specific biomarkers using the original newborn screen specimen (second-tier test). Nevertheless, abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis, independent biochemical (ie, in vitro enzyme assay) or molecular genetic analyses are required, many of which are offered within Mayo Clinic's Division of Laboratory Genetics and Genomics.


The reports are in text form only. In a case with a completely normal profile, where the interpretation is reported as negative for all of the listed groups of conditions, no values are provided. A report for an abnormal screening result includes a quantitative result for the relevant abnormal biomarkers including those of a second-tier test when applicable, the CLIR score indicating the similarity of the newborn’s results to those derived from known patients with the relevant disease, a detailed interpretation of the results, and recommendations for additional biochemical testing and confirmatory studies (enzyme assay, molecular analysis).

Clinical Reference

1. DeJesus VR, Zhou H, Vogt RF, Hannon WH: Changes in solvent composition in tandem mass spectrometry multiplex assay for lysosomal storage disorders do not affect assay results. Clin Chem 2009;55(3):596-598

2. Li Y, Scott CR, Chamoles NA, et al: Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin Chem 2004;50(10):1785-1796

3. Matern D, Gavrilov D, Oglesbees D, et al: Newborn screening for lysosomal storage disorders. Semin Perinatol. 2015 Apr;39(3):206-216

4. Part 16 Lysosomal Disorders. In Scriver's The Online Metabolic and Molecular Basis of Inherited Disease (OMMBID). Edited by D Valle, AL Beaudet, B Vogelstein, SE Antonarakis, et al. McGraw-Hill Medical Division. Accessed 11/20/2017. Available at

5. Minter Baerg M, Stoway SD, Hart J, et al: Precision newborn screening for lysosomal disorders. Genet Med. 2017 Nov 9. doi:10.1038/gim.2017.194

Day(s) and Time(s) Performed

Monday through Sunday; 11:30 a.m.

Analytic Time

2 days

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 U.S. Food and Drug Administration.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
LSD6 Lysosomal Newborn Screen, BS 62301-7


Result ID Test Result Name Result LOINC Value
38341 Lysosomal Newborn Screen Result 62301-7
38522 Reviewed By 18771-6
BG679 Birth Weight (grams, XXXX) 8339-4
BG680 Time of Birth (24hr Time, XX:XX) 57715-5
BG681 Gestational Age (weeks, XX.X) 76516-4
BG683 Reviewed By 59462-2


Biochemical Genetics Patient Information (T602) in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information: