Sign in →

Test ID: 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)

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: 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.

Useful For

Follow up for abnormal biochemical results suggestive of congenital lactic acidosis

 

Establishing a molecular diagnosis for patients with congenital lactic acidosis

 

Identifying variants within genes known to be associated with congenital lactic acidosis, allowing for predictive testing of at-risk family members

Genetics Test Information

This test utilizes next-generation sequencing (NGS) to detect single nucleotide and copy number variants in 28 genes associated with congenital lactic acidosis: ACAD9, AGK, DLD, ECHS1, FBXL4, FLAD1, FOXRED1, GFER, HADHA, HADHB, HLCS, MRPL3, MRPS22, NDUFB11, NDUFS4, OGDH, PC, PDHA1, PDHX, PDP1, SLC19A2, SLC19A3, SLC25A19, SUCLG1, TMEM70, TPK1, UQCRC2, VARS2.

 

See Targeted Genes and Methodology Details for Congenital Lactic Acidosis Panel in Special Instructions and Method Description for additional details.

 

Additionally, mitochondrial genome sequencing including amplification of the entire mitochondrial genome by long-range polymerase chain reaction (LRPCR) followed by sequencing on the NGS platform is included to evaluate for variants within the mitochondrial genome.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for disorders causing congenital lactic acidosis.

 

Additional first tier testing may be considered/recommended. For more information see Ordering Guidance.

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)

Reporting Name

Congenital Lactic Acidosis Panel

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

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.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) 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. Bravo-Alonso I, Navarrette R, Vega AI, et al: Genes and variants underlying human congenital lactic acidosis-from genetics to personalized treatment. J Clin Med. 2019;8(11):1811

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

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)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CLADP Congenital Lactic Acidosis Panel 105352-9

 

Result ID Test Result Name Result LOINC Value
608632 Test Description 62364-5
608633 Specimen 31208-2
608634 Source 31208-2
608635 Result Summary 50397-9
608636 Result 82939-0
608637 Interpretation 69047-9
608638 Resources 99622-3
608639 Additional Information 48767-8
608640 Method 85069-3
608641 Genes Analyzed 48018-6
608642 Disclaimer 62364-5
608643 Released By 18771-6

Day(s) Performed

Varies

Report Available

28 to 42 days

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Mayo Clinic Laboratories | Genetics and Genomics Additional Information:

mcl-moltechtestmenu