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Glutathione Synthetase Deficiency via the GSS Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
GSS 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8205GSS81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Glutathione synthetase deficiency is the most common inborn error of the synthesis of glutathione. According to clinical severity, the disease has been classified as mild, moderate or severe (Njålsson 2005; Ristoff and Larsson. 2007). The mild form is alternatively termed hemolytic anemia due to glutathione synthetase deficiency, with only the presentation of hemolytic anemia. The moderate form usually presents with severe chronic metabolic acidosis and 5-oxoprolinuria with mild or moderate hemolytic anemia in the neonatal stage. In addition to all manifestations of the moderate form, patients with severe glutathione synthetase deficiency typically develop progressive neurological symptoms including psychomotor retardation, mental retardation, seizures, spasticity, ataxia, and intention tremor. Some patients also have recurrent bacterial infections. Retinal dystrophy has been also found in some adult patients. Other less frequent clinical manifestations include antenatal cerebral haemorrhage, low levels of cysteinyl leukotrienes and multiple malformations. Age at onset of the disease ranges from the first days of life to childhood (Simon et al. 2009). Early death in the neonatal stage due to infection and electrolyte imbalance has been reported in about 25% of patients with glutathione synthetase deficiency.


Glutathione synthetase deficiency is an autosomal recessive disorder caused by defects in the GSS gene (Shi et al. 1996). GSS has 12 coding exons that encode glutathione synthetase, the enzyme catalyzing the last step of glutathione synthesis. The majority of GSS defects are missense and splicing site mutations, accounting for approximately 60% and 28% of all documented pathogenic alleles respectively (Human Gene Mutation Database). Small deletion/insertions and one nonsense mutation have been also found in GSS, but much less frequently. Although GSS defects have been found across the whole coding region of the gene, the majority of missense mutations are clustered at the region of exons 5 to 10 (Dahl et al. 1997; Njålsson 2005). The mild form of the disease is correlated with pathogenic mutations affecting enzymatic stability (Njålsson 2005).

Clinical Sensitivity - Sequencing with CNV PGxome

Biallelic GSS mutations were found in the coding exons and exon-intron boundaries of the gene in about 77% (23 out of 30) of patients with glutathione synthetase deficiency (Njålsson et al. 2003).

Testing Strategy

This test provides full coverage of all coding exons of the GSS gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

In addition, we also target-sequence the following documented pathogenic mutations that cannot be detected via the above sequencing: c.-9+5G>A and c.129+1663 A>G (Human Gene Mutation Database).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with glutathione synthetase deficiency. Testing is also indicated for family members of patients who have known GSS mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GSS.


Official Gene Symbol OMIM ID
GSS 601002
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Dahl N, Pigg M, Ristoff E, Gali R, Carlsson B, Mannervik B, Larsson A, Board P. 1997. Missense mutations in the human glutathione synthetase gene result in severe metabolic acidosis, 5-oxoprolinuria, hemolytic anemia and neurological dysfunction. Human molecular genetics 6: 1147–1152. PubMed ID: 9215686
  • Human Gene Mutation Database (Bio-base).
  • Njålsson R, Carlsson K, Winkler A, Larsson A, Norgren S. 2003. Diagnostics in patients with glutathione synthetase deficiency but without mutations in the exons of the GSS gene. Human Mutation 22: 497–497. PubMed ID: 14635114
  • Njålsson R. 2005. Glutathione synthetase deficiency. Cellular and Molecular Life Sciences 62: 1938–1945. PubMed ID: 15990954
  • Ristoff E, Larsson A. 2007. Inborn errors in the metabolism of glutathione. Orphanet Journal of Rare Diseases 2: 16. PubMed ID: 17397529
  • Shi ZZ, Habib GM, Rhead WJ, Gahl WA, He X, Sazer S, Lieberman MW. 1996. Mutations in the glutathione synthetase gene cause 5-oxoprolinuria. Nat. Genet. 14: 361–365. PubMed ID: 8896573
  • Simon E, Vogel M, Fingerhut R, Ristoff E, Mayatepek E, Spiekerkötter U. 2009. Diagnosis of glutathione synthetase deficiency in newborn screening. Journal of Inherited Metabolic Disease 32: 269–272. PubMed ID: 19728142


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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View Ordering Instructions

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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