Test ID: HCMM
Homocysteine (Total), Methylmalonic Acid, and Methylcitric Acid, Blood Spots
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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 and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Homocystinuria
Methyl Citric Acid
Methylmalonic Acidemia
Methylmalonic Aciduria (MMA)
MMA (Methylmalonic Aciduria)
PA (Propionic Acidemia)
Propionic Academia (PA)
Propionic Aciduria
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: Local newborn screening card
Specimen Volume: 2 blood spots
Collection Instructions:
1. Do not use device or capillary tube containing EDTA to collect specimen.
2. At least 1 spot should be complete, unpunched.
3. An alternative blood collection option for patients >1 year of age is fingerstick. Include type of feeding information on the collection card.
4. Do not expose specimen to heat or direct sunlight.
5. Do not stack wet specimens.
6. Keep specimen dry.
7. If collection of a new specimen is necessary, let blood dry on the Supplemental Newborn Screening Card (Supply T493) at ambient temperature in a horizontal position for 3 hours.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole blood | Ambient (preferred) | |
| Frozen | ||
| Refrigerated | ||
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 in cystathionine beta-synthase. This enzyme is involved in the condensation of homocysteine and serine to form cystathionine as part of methionine metabolism. The incidence of homocystinuria is approximately 1 in 350,000 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.
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: <15.0 nmol/mL
Methylmalonic acid: <5.0 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.
In a Mayo study that analyzed 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).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A metabolic specialist should always be involved in the care of an affected patient
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Rinaldo P, Hahn S, Matern D: Tietz Textbook of Clinical Chemistry. 5th Edition. Edited by CA Burtis, ER Ashwood, DE Burns. St. Louis MO, Elsevier Sanders Company, 2006, pp 2207-2247
2. Watkins D, Rosenblatt DS: Cobalamin and inborn errors of cobalamin absorption and metabolism. Endocrinologist 2001;11:98-104
Method Description Describes how the test is performed and provides a method-specific reference
A single 3/16-inch dried blood spot punch is extracted with an acidified acetonitrile and water solution containing dithiotheritol, d3-methylmalonic acid, d3-methycitric acid, and d8-homocystine. During 1 hour of agitation, free homocystine, protein-bound homocysteine, and the added d8-homocystine internal standard are reduced to homocysteine. The extract is transferred and then evaporated under heated nitrogen. Dried residue is treated with 3 N HCl in n-butanol to form butylesters. After evaporation of the butanol, the residue is reconstituted, centrifuged, and the supernatant is transferred to microvials and subjected to liquid chromatography-tandem mass spectrometry analysis. (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;56(11): in press PMID: 20807894)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday at 8 a.m., Thursday at 11 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83090-Homocysteine
83918-Methylmalonic acid and methylcitric acid
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 50246 | Specimen | 31208-2 |
| 50247 | Specimen ID | N/A |
| 50248 | Source | N/A |
| 50249 | Order Date | N/A |
| 50250 | Reason For Referral | 42349-1 |
| 50251 | Method | In Process |
| 50252 | Homocysteine | 13965-9 |
| 50253 | Methylmalonic Acid | 13964-2 |
| 50254 | Methylcitric Acid | 26904-3 |
| 50255 | Interpretation | 59462-2 |
| 50256 | Amendment | In Process |
| 50257 | Reviewed By | N/A |
| 50258 | Release Date | N/A |
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