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Test ID: NCLP Neuronal Ceroid Lipofuscinosis (NCL, Batten Disease) Panel by Next-Generation Sequencing

Useful For

Follow up for abnormal biochemical or electron microscopy results suspicious for neuronal ceroid lipofuscinoses (NCLs)

 

Identifying mutations within genes known to be associated with NCL, allowing for predictive testing of at-risk family members

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No
CULAF Amniotic Fluid Culture/Genetic Test Yes No
MATCC Maternal Cell Contamination, B Yes No

Testing Algorithm

See clinical information for recommended first-tier biochemical testing.

 

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

 

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

Method Name

Custom Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

Reporting Name

NCL (Batten Disease) Panel

Specimen Type

Varies


Advisory Information


Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing.



Additional Testing Requirements


All prenatal specimens must be accompanied by a maternal blood specimen.

-       Order MATCC / Maternal Cell Contamination, Molecular Analysis on the maternal specimen.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.

 

Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. CST on Friday in order to be processed appropriately.



Specimen Required


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.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

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

 

Prenatal Specimens

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

 

Acceptable

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

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. 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:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

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

Specimen Volume: 3 to 5 Blood Spots on collection card

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


Specimen Minimum Volume

Blood: 1 mL; Blood Spots: 3, 3-mm diameter; Amniotic Fluid: 10 mL; Chorionic Villi: 5 mg

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Neuronal ceroid lipofuscinoses (NCLs) are a subset of lysosomal storage diseases that involve defective cellular processing of lipids. NCLs are clinically characterized by epilepsy, intellectual and motor decline, and blindness. Electron microscopy typically shows a characteristic accumulation of granular osmophilic deposits (GROD), curvilinear profiles (CVB), or fingerprint profiles (FP). Enzymatic testing may show deficiency in palmitoyl-protein thioesterase 1 (PPT1), tripeptidyl-peptidase 1 l(TPP1), or cathepsin D (CTSD). Currently there are at least 14 genetically distinct forms.

 

Age of onset and clinical features can be variable, from congenital to adult onset. NCL is typically inherited in an autosomal recessive manner, although one adult onset form (ANCL; DNAJC5 gene) has been shown to be autosomal dominant.

 

First-tier biochemical testing is available for the 2 most common types of enzyme deficiency resulting in NCL: TPPTL / Tripeptidyl Peptidase 1 (TPP1) and Palmitoyl-Protein Thioesterase 1 (PPT1), Leukocytes; and TPPTF / Tripeptidyl Peptidase 1 (TPP1) and Palmitoyl-Protein Thioesterase 1 (PPT1), Fibroblasts.

 

Note: Testing for these 15 genes is also included in the LSDP / Lysosomal Storage Disease Panel by Next-Generation Sequencing.

 

Gene

Disease Name/Locus Name

OMIM

Inheritance

ATP13A2

Ceroid lipofuscinosis, neuronal, 12/Kufor-Rakeb syndrome

606693

AR

CLN3

Ceroid lipofuscinosis, neuronal, 3

204200

AR

CLN5

Ceroid lipofuscinosis, neuronal, 5

256731

AR

CLN6

Ceroid lipofuscinosis, neuronal, 6

601780

AR

CLN8

Ceroid lipofuscinosis, neuronal, 8

600143

AR

CTSD

Ceroid lipofuscinosis, neuronal, 10

610127

AR

CTSF

Ceroid lipofuscinosis, neuronal, 13, Kufs type

615362

AR

CTSK

Pycnodysostosis

265800

AR

DNAJC5

Ceroid lipofuscinosis, neuronal, 4, Parry type

162350

AD/AR

GRN

Ceroid lipofuscinosis, neuronal, 11

614706

AR

KCTD7

Ceroid lipofuscinosis, neuronal, 14

611726

AR

MFSD8

Ceroid lipofuscinosis, neuronal, 7

610951

AR

PANK2

HARP syndrome

606157

AR

PPT1

Ceroid lipofuscinosis, neuronal, 1

256730

AR

TPP1

Ceroid lipofuscinosis, neuronal, 2

204500

AR

AR=autosomal recessive

AD=autosomal dominant

Reference Values

An interpretive report will be provided.

Interpretation

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

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

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. Mole SE, Cotman SL: Genetics of the neuronal ceroid lipofuscinoses (Batten disease). Biochim Biophys Acta 2015;1852(10PtB):2237-2241

3. Cooper JD, Tarczyluk MA, Nelvagal HR: Towards a new understanding of NCL pathogenesis. Biochim Biophys Acta 2015;1852(10PtB):2256-2261

4. Williams RE, Mole SE: New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology 2012;79(2):183-191

5. Mole SE, Williams RE: Neuronal Ceroid-Lipofuscinoses. In Pagon RA, Edited by MP Adam, HH Ardinger. GeneReviews. Seattle, University of Washington, Seattle; 1993-2015. Available at www.ncbi.nlm.nih.gov/books/NBK1428/

Day(s) and Time(s) Performed

Performed weekly, Varies

Analytic Time

4 weeks

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

81406

81479

Fibroblast Culture for Genetic Test

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

88240-Cryopreservation (if appropriate)

 

Amniotic Fluid Culture/Genetic Test

88235-Tissue culture for amniotic fluid (if appropriate)

88240-Cryopreservation (if appropriate)

 

Maternal Cell Contamination, B

81265-Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (eg, pre-transplant recipient and donor germline testing, post-transplant non-hematopoietic recipient germline [eg, buccal swab or other germline tissue sample] and donor testing, twin zygosity testing or maternal cell contamination of fetal cells (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
NCLP NCL (Batten Disease) Panel In Process

 

Result ID Test Result Name Result LOINC Value
41768 Result Summary 50397-9
41769 Result In Process
41770 Interpretation In Process
41771 Additional Information 48767-8
41772 Specimen 31208-2
41773 Source 31208-2
41774 Released By No LOINC Needed

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

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-inherited-molecular