S-Adenosylhomocysteine Hydrolase Deficiency via the AHCY 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
8183 AHCY 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8183AHCY81479 81479 $890 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.

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

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Defects in the S-Adenosylhomocysteine Hydrolase (AHCY) enzyme have been shown to lead to persistent, isolated hypermethioninemia, which is the elevation of methionine in plasma without accompanying homocystinemia. This hypermethioninemia persists beyond the first months of life (Mudd et al. 2001). A relatively small number of patients have been reported in the literature and thus a cohesive clinical picture has yet to develop, but thus far, all patients have been reported to present with hypotonia and myopathy, along with elevated creatine kinase (CK) levels. Other clinical features observed in affected patients have included severe developmental delays, contractures, poor head control, white matter or other brain abnormalities, microcephaly, behavioral difficulties (including obsessive behavior, severe attention deficit, aggression and self-injurious behavior), poor feeding, respiratory insufficiency, liver abnormalities, and in one family, fetal hydrops. Biochemically, patients present with elevated methionine levels and greatly increased S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) levels. In some cases, slight increases in plasma total homocysteine (tHcy), cystathionine and sarcosine were observed. In all patients, low activity of the S-adenosylhomocysteine hydrolase was confirmed (Baric et al. 2004; Buist et al. 2006; Grubbs et al. 2010; Honzík et al. 2012; Strauss et al. 2015).

Plasma methionine levels in reported patients have not always exceeded reference levels in early infancy, although they do increase with time. Therefore, AHCY deficient patients may or may not be detected via newborn screening (Mudd 2011). Treatment via dietary measures has been attempted, although there is no conclusive evidence that such treatment affects the clinical outcome (Baric et al. 2004; Buist et al. 2006). Liver transplantation has been reported to be beneficial in one case (Strauss et al. 2015).

Genetics

S-adenosylhomocysteine hydrolase deficiency is inherited in an autosomal recessive manner, and is caused by pathogenic variants in the AHCY gene located on chromosome 20 at 20q11.22. Fewer than 10 pathogenic variants have been reported in the AHCY gene. Thus far, all reported variants are missense variants, with the exception of one nonsense variant (Baric et al. 2004; Human Gene Mutation Database). The variants Arg49Cys and Tyr143Cys have both been reported in more than one family; all other variants reported to date have been observed only in a single family (Baric et al. 2004; Buist et al. 2006; Vugrek et al. 2009; Honzík et al. 2012; Strauss et al. 2015).

The S-adenosylhomocysteine hydrolase (AHCY) enzyme is responsible for the hydrolysis of S-adenosylhomocysteine (AdoHcy) to adenosine and homocysteine (Baric et al. 2004; Mudd 2011). This reaction is a part of the transmethylation and transsulfuration pathways, which are necessary for recycling methionine, generating methyl groups for methyltransfer reactions, and the generation of cysteine (Mudd et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, the sensitivity of this test is difficult to estimate due to the low number of cases reported in the literature. Analytical sensitivity may be high as the only reported causative variants are detectable by sequencing (Baric et al. 2004; Buist et al. 2006; Grubbs et al. 2010; Honzík et al. 2012; Strauss et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the AHCY 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with hypermethioninemia are good candidates for this test, particularly if they have elevated plasma AdoHcy and AdoMet levels and normal or only slightly elevated plasma homocysteine, tyrosine and sarcosine levels. Family members of patients known to have AHCY pathogenic variants are also good candidates, and we will also sequence the AHCY gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
AHCY 180960
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Baric et al. 2004. PubMed ID: 15024124
  • Buist et al. 2006. PubMed ID: 16736098
  • Grubbs et al. 2010. PubMed ID: 20852937
  • Honzík et al. 2012. PubMed ID: 22959829
  • Human Gene Mutation Database (Bio-base).
  • Mudd et al. 2001. PubMed ID: 11596649
  • Mudd et al. 2014. Disorders of Transsulfuration. In: Valle D, Beaudet AL, Vogelstein B, et al., editors.New York, NY: McGraw-Hill. OMMBID. 
  • Mudd. 2011. PubMed ID: 21308989
  • Strauss et al. 2015. PubMed ID: 26095522
  • Vugrek O. et al. 2009. Human Mutation. 30: E555-65. PubMed ID: 19177456

Ordering/Specimens

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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