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Test ID: MHDZ Methylmalonic Aciduria and Homocystinuria, cblD Type, Full Gene Analysis, Varies

Useful For

Confirmation of diagnosis of disorders belonging to the cblD complementation group


Distinguishing between cblC, cblD, and cblF types when methylmalonic aciduria and homocystinuria are identified


Distinguishing between cblA, cblB, and cblD variant 2 when methylmalonic aciduria is identified


Distinguishing between cblD variant 1, cblE, and cblG when homocystinuria is identified


Carrier screening in cases where there is a family history of methylmalonic aciduria or homocystinuria, but disease-causing mutations have not been identified in an affected individual

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes No
CRYOB Cryopreserve for Biochem Studies No No

Testing Algorithm

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reporting Name

MMADHC Gene, Full Gene Analysis

Specimen Type


Shipping Instructions

Specimen preferred to arrive within 96 hours of draw.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.


Submit only 1 of the following specimens:



Specimen Type: Whole blood


Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated/Frozen


Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours


Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient


Specimen Type: Blood spot

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


Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper, or Blood Spot Collection Card (T493)

Specimen Volume: 2 to 5 Blood Spots on collection card (Whatman Protein Saver 903 Paper; Ahlstrom 226 filter paper; or Blood Spot Collection Card, T493)

Collection Instructions:

1. An alternative blood collection option for a patient >1 year of age is finger stick.

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

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

4. Do not stack wet specimens.

5. Keep specimen dry

Specimen Stability Information: Ambient (preferred)/Refrigerated

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.

Specimen Minimum Volume

Blood: 1 mL
Blood Spots: 5 punches, 3-mm diameter

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

Several causes of inborn errors of cobalamin (cbl; better known as vitamin B12) metabolism have been identified. These disorders have been classified into 8 distinct complementation classes (cblA-cblH). Complementation analysis utilizes cells from the patient to determine at what stage of the cbl metabolism pathway an error is occurring, and uses this information to differentiate between the various complementation class disorders. Depending on the complementation class involved, errors in cbl metabolism can result in methylmalonic aciduria, homocystinuria, or both.


cblD type is a rare autosomal recessive disorder with variable clinical presentations. It can present as cblD variant 1, associated with isolated homocystinuria; cblD variant 2, associated with isolated methylmalonic aciduria; or as cblD combined, associated with both methylmalonic aciduria and homocystinuria. cblD variant 1 is associated with clinical features of isolated homocystinuria, including megaloblastic anemia and neurological abnormalities, as well as developmental delays. cblD variant 2 is associated with clinical features of isolated methylmalonic aciduria, including metabolic decomposition, which can result in lethargy, failure to thrive, feeding problems, and hypotonia. cblD combined is associated with clinical features of both methylmalonic aciduria and homocystinuria. Biochemical presentation includes methylmalonic aciduria and/or homocystinuria in urine organic acid or plasma amino acid analysis.(1) Other complementation class disorders can result in a similar biochemical phenotype, and complementation testing or molecular testing is utilized to distinguish between these different types.


Mutations in the MMADHC gene are responsible for the cblD type disorder. To date, 9 mutations in 7 individuals have been identified.(2) Three missense mutations identified in exons 6 and 8 have been associated with cblD variant 1. One nonsense mutation, 1 in-frame duplication, and 1 frame-shift deletion in exons 3 and 4 have been associated with cblD variant 2. One nonsense mutation, 1 frame-shift duplication, and 1 splice-site deletion in exons 5 and 8 and intron 7 have been associated with cblD combined.

Reference Values

An interpretive report will be provided.


All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Suormala T, Baumgartner MR, Coelho D, et al: The cblD Defect Causes Either Isolated or Combined Deficiency of Methylcobalamin and Adenosylcobalamin Synthesis. J Biol Chem 2004;279(41):42742-42749

3. Coelho D, Suormala T, Stucki M, et al: Gene Identification for the cblD Defect of Vitamin B12 Metabolism. N Engl J Med 2008;358:1454-1464

4. Goodman SI, Moe PG, Hammond KB, et al: Homocystinuria with methylmalonic aciduria: two cases in a sibship. Biochem Med 1970;4(5):500-515

5. Cooper BA, Rosenblatt DS, Watkins D: Methylmalonic Aciduria Due to a New Defect in Adenosylcobalamin Accumulation by Cells. Am J Hematol 1990;34:115-120

Day(s) Performed


Report Available

14 to 20 days

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 US Food and Drug Administration.

CPT Code Information

81479-Unlisted molecular pathology procedure


Fibroblast Culture for Genetic Test

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MHDZ MMADHC Gene, Full Gene Analysis 94207-8


Result ID Test Result Name Result LOINC Value
53992 Result Summary 50397-9
53993 Result 82939-0
53994 Interpretation 69047-9
53995 Additional Information 48767-8
53996 Specimen 31208-2
53997 Source 31208-2
53998 Released By 18771-6


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

3. If not ordering electronically, complete, print, and send a Benign Hematology Test Request Form (T755) with the specimen.

Mayo Clinic Laboratories | Hematology Catalog Additional Information: