NCL Diagnostic Algorithm

Any samples for NCL diagnosis and any questions regarding diagnosis can be sent to the DEM-CHILD coordinator. Also, under the following phone numer, you can receive immediate advice regarding any patient or diagnosis related questions:

 

Dr. Angela Schulz

DEM-CHILD coordinator

Children's Hospital

University Medical Center Hamburg-Eppendorf

Martinistrasse 52

D-20246 Hamburg, Germany

 

Phone: +49-40-74105-6391

Fax: +49-40-74015-5137

Email: anschulz@uke.de

 

 

Clinical presentation

Necessary diagnostic tests

Possibly affected genes

Newborn

with epilepsy and microcephaly

 

Enzyme testing for cathepsin D (CtsD) (leucocytes of fibroblasts)

CtsD deficient: CLN10

Young child

(>6 months) with developmental stillstand or regression and / or newly occuring severe epilepsy of unknown cause

enzyme testing for PPT1 and TPP1 (dry blood spots; confirmation in leucocytes or fibroblasts)

 

 

PPT1

PPT1 deficient: CLN1

 

TPP1

TPP1 deficient: CLN2

 

If PPT1 and TPP1 enzyme activity is normal: Electron microscopic examination (skin biopsy or lymphocytes): If storage material is present: genetic testing.

CLN5

CLN6

CLN7

CLN8

CLN14 (KCTD7)

School child

with visual loss and / or dementia and epilepsy

Search for lymphocyte vacuoles (light microscopy of blood smear). If lymphocyte vacuoles are present: genetic testing of the CLN3 gene

 

CLN3

 

If no lymphocyte vacuoles, enzyme testing for PPT1, TPP1 and CtsD (see above)

PPT1 deficient: CLN1

TPP1 deficient: CLN2

CtsD deficient: CLN10

 

If PPT1 and TPP1 enzyme activity is normal: Electron microscopic examination  (skin biopsy or lymphocytes). If storage material is present: genetic testing.

CLN5

CLN6

CLN7

CLN8

CLN12 (ATP13A2)

Young adult

with non-specific mental, motor or behavioural abnormalities.

Enzyme testing for PPT1, TPP1 and CtsD (see above)

 

PPT1 deficient: CLN1

TPP1 deficient: CLN2

CtsD deficient: CLN10

 

 

If PPT1 and TPP1 enzyme activity is normal: Electron microscopic examination (skin biopsy or lymphocytes). If storage material is present: genetic testing (eventually in special cases even without detection of storage material), consider possible mode of inheritance.

 

If autosomal dominant:

CLN4 (DNAJC5)

If autosomal recessive :

CLN6

CLN11 (GRN)

CLN13 (CTSF)