Test Catalog

Test Id : HCMM

Homocysteine (Total), Methylmalonic Acid, and Methylcitric Acid, Blood Spot

Useful For
Suggests clinical disorders or settings where the test may be helpful

Second-tier assay of newborn screening specimens when abnormal propionyl carnitine or methionine concentrations are identified in a primary newborn screen

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

HCMM, BS

Aliases
Lists additional common names for a test, as an aid in searching

HCY

Homocystinuria

Methyl Citric Acid

Methylmalonic Acidemia

Methylmalonic Aciduria (MMA)

MMA (Methylmalonic Aciduria)

PA (Propionic Acidemia)

Propionic Aciduria

Propionic Acidemia (PA)

Specimen Type
Describes the specimen type validated for testing

Whole blood

Ordering Guidance

The preferred test for evaluating adults for an inherited disorder of methionine, cobalamin, or propionate metabolism is CMMPP / Cobalamin, Methionine, and Methylmalonic Acid Pathways, Plasma or CMMPS / Cobalamin, Methionine, and Methylmalonic Acid Pathways, Serum.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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

Container/Tube:

Preferred: Card-Blood Spot Collection (Filter Paper) from heel or finger stick

Acceptable: Local newborn screening card, Whatman Protein Saver 903 paper

Specimen Volume: 2 Blood spots

Collection Instructions:

1. Do not use device or capillary tube containing EDTA or ACD to collect specimen. Sodium heparin is acceptable, but must be spotted on card the same day as collected.

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

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

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

5. Do not stack wet specimens.

6. Keep specimen dry.

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.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 Blood spot

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Shows serum rings; Insufficient specimen Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole blood Ambient (preferred) FILTER PAPER
Frozen FILTER PAPER
Refrigerated FILTER PAPER

Useful For
Suggests clinical disorders or settings where the test may be helpful

Second-tier assay of newborn screening specimens when abnormal propionyl carnitine or methionine concentrations are identified in a primary newborn screen

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Homocystinuria is an autosomal recessive disorder caused by a deficiency of the enzyme cystathionine beta-synthase. The incidence of homocystinuria is approximately 1 in 200,000 to 335,000 live births. Classical homocystinuria is characterized by a normal presentation at birth followed by failure to thrive and developmental delay. Untreated homocystinuria can lead to ophthalmological problems, mental retardation, seizures, thromboembolic episodes, and skeletal abnormalities. The biochemical phenotype is characterized by increased plasma concentrations of methionine and homocysteine (free and total) along with decreased concentrations of cystine.

 

Methylmalonic acidemia (MMA) and propionic acidemia (PA) are defects of propionate metabolism caused by deficiencies in methylmalonyl-CoA mutase and propionyl-CoA carboxylase, respectively. The clinical phenotype includes vomiting, hypotonia, lethargy, apnea, hypothermia, and coma. The biochemical phenotype for MMA includes elevations of propionyl carnitine, methylmalonic acid, and methylcitric acid. Patients with PA will have elevations of propionyl carnitine and methylcitric acid with normal methylmalonic acid concentrations as the enzymatic defect is upstream of methylmalonic-CoA mutase.

 

Newborn screening for inborn errors of methionine and propionic acid metabolism relies on elevations of methionine and propionyl carnitine. These analytes are not specific for these conditions and are prone to false-positive results, leading to increased cost, stress, and anxiety for families who are subjected to follow-up testing. Homocysteine, methylmalonic acid, and methylcitric acid are more specific markers for inborn errors of methionine and propionic acid metabolism. Molecular genetic testing can be used to confirm a biochemical diagnosis for homocystinuria, methylmalonic acidemia, and propionic acidemia.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

HOMOCYSTEINE:

<9.0 nmol/mL

 

METHYLMALONIC ACID:

<4.0 nmol/mL

 

METHYLCITRIC ACID:

<1.0 nmol/mL

 

An interpretive report will also be provided.

Interpretation
Provides information to assist in interpretation of the test results

Elevated homocysteine, methylcitric acid, or methylmalonic acid concentrations are indicative of an underlying metabolic disorder.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Normal levels may be seen in affected individuals undergoing treatment.

Supportive Data

In a Mayo study that analyzed specimens from 200 unaffected neonates, clear clinical discrimination was observed when compared to patients with defects of propionate or methionine metabolism. The 99.5 percentile, determined from the analysis of 200 dried blood spots of unaffected controls, for methylmalonic acid (MMA), methylcitric acid (MCA), and homocysteine (HCY), are 1.58 nmol/mL, 0.62 nmol/mL, and 9.9 nmol/mL, respectively, providing clear clinical discrimination from patients with defects of propionate or methionine metabolism (eg, methylmalonic acidemia: MMA=31.9 nmol/mL; propionic acidemia: MCA=12.8 nmol/mL; homocystinuria: HCY=189 nmol/mL).

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Pasquali M, Longo N: Newborn screening and inborn errors of metabolism. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:1697-1730

2. Tortorelli S, Turgeon CT, Lim JS, et al: Two-tier approach to the newborn screening of methylenetetrahydrofolate reductase deficiency and other remethylation disorders with tandem mass spectrometry. J Pediatr. 2010;157(2):271-275

3. Harvey Mudd S, Levy HL, Kraus JP: Disorders of transsulfuration. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed September 17, 2020. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225084718

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Total homocysteine, 2-methylcitric acid,  and methylmalonic acid are measured by stabile isotope dilution microflow liquid chromatography tandem mass spectrometry.(Turgeon CT, Magera MJ, Cuthbert CD, et al: Determination of total homocysteine, methylmalonic acid, and 2-methylcitric acid in dried blood spots by tandem mass spectrometry. Clin Chem. 2010 Nov; 56[11]:1686-1695)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Thursday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 4 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

1 year

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83090

83918

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports