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Test ID: HCMM Homocysteine (Total), Methylmalonic Acid, and Methylcitric Acid, Blood Spots

Reporting Name

HCMM, BS

Useful For

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

Specimen Type

Whole blood


Specimen Required


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

Container/Tube:

Preferred: Card-Blood Spot Collection (Filter Paper)

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.

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 room 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.


Specimen Minimum Volume

Blood Spots: 1

Specimen Stability Information

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

Reference Values

Homocysteine: <15.0 nmol/mL

Methylmalonic acid: <5.0 nmol/mL

Methylcitric acid: <1.0 nmol/mL

An interpretive report will also be provided.

Day(s) and Time(s) Performed

Monday, Thursday; 8 a.m.

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

83090-Homocysteine

83918-Methylmalonic acid and methylcitric acid

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HCMM HCMM, BS In Process

 

Result ID Test Result Name Result LOINC Value
50246 Specimen 31208-2
50247 Specimen ID 57723-9
50248 Source 31208-2
50249 Order Date 82785-7
50250 Reason For Referral 42349-1
50251 Method 49549-9
50252 Homocysteine 54301-7
50253 Methylmalonic Acid 82385-6
50254 Methylcitric Acid 82386-4
50255 Interpretation 59462-2
50256 Amendment In Process
50257 Reviewed By No LOINC Needed
50258 Release Date 82772-5

Clinical Information

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.

Interpretation

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).

Clinical Reference

1. Rinaldo P, Hahn S, Matern D: Tietz Textbook of Clinical Chemistry. Fifth 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

3. Turgeon CT, Magera MJ, Cuthbert CD, et al: Simultaneous Determination of Total Homocysteine, Methylmalonic Acid, and 2-Methylcitric Acid in Dried Blood Spots by Tandem Mass Spectrometry. Clin Chem 2010;56:1686-1695

4. 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;157:271-275

5. Harvey Mudd SS, Levy HL, Kraus JP, et al: Disorders of Transsulfuration. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, KW Kinzler, SE Antonarakis, A Ballabio, K Gibson, G Mitchell. New York, NY: McGraw-Hill;2014. Accessed May 08, 2017. Available from http://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62675596

Analytic Time

2 days

Method Name

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

Forms

1. 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 (T576) is available in Special Instructions.

2. Biochemical Genetics Patient Information (T602) in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical