Test Code CLADP Congenital Lactic Acidosis Panel, Varies

Ordering Guidance

The recommended first-tier tests to screen for an underlying biochemical etiology for congenital lactic acidosis (CLA) are a combination of the following:

Lactic acid in blood

LASF1 / Lactic acid, Spinal Fluid

ACRN / Acylcarnitines, Quantitative, Plasma

OAU /Organic Acids Screen, Random, Urine

AAQP / Amino Acids, Quantitative, Plasma

PDHC / Pyruvate Dehydrogenase Complex, Fibroblasts

Pyruvate carboxylase activity

Customization of this panel and single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

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

Container/Tube:

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. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

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.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

Specimen Type: Cultured fibroblast

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

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

Specimen Type: Blood spot

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

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 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. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

2. For collection instructions, see Blood Spot Collection Instructions

3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)

4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)

Forms

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 Biochemical Genetics Test Request (T798) with the specimen.

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing/Long-Range Polymerase Chain Reaction (L-RPCR) followed by Next-Generation Sequencing (NGS)

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type	Temperature	Time
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Congenital lactic acidosis (CLA) is a rare, but serious, condition that presents in newborns with extreme elevations of lactic acid and is caused by a variety of biochemical disorders, resulting in impaired mitochondrial activity. Elevated lactate in multiple specimen types such as blood and cerebrospinal fluid (CSF) are typically observed. However, additional symptoms are extremely variable, as any high-energy organ or tissue may be impaired, resulting in a need for multisystem screening that may involve biopsies and biochemical analysis. CLA can be caused by pathogenic variants in genes encoding enzymes involved in gluconeogenesis, pyruvate oxidation, the Krebs cycle, and mitochondrial function.

A comprehensive gene panel with mitochondrial genome analysis is an essential tool to establish a diagnosis for patients with congenital lactic acidosis. As biomarker testing and multisystem organ assessments are not specific and can yield complex results, genetic testing is required to distinguish among the spectrum of conditions that can cause CLA. This panel analyzes a combination of nuclear genes for single-gene biochemical disorders known to cause CLA, as well as analysis of the mitochondrial genome.

Reference Values

An interpretive report will be provided.

Performing Laboratory

Mayo Clinic Laboratories in Rochester

CPT Code Information

81443

81460

81465

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

88240-Cryopreservation (if appropriate)

81479 (if appropriate for government payers)

Day(s) Performed