Table 2.
Diagnostic Algorithm for NCL Diseases
| Clinical presentation | Necessary diagnostic tests | Possibly affected genes |
|---|---|---|
|
Newborn
With epilepsy and microcephaly |
Enzyme testing for cathepsin D (CtsD) (leucocytes fibroblasts) | CtsD deficient: CLN10 |
|
Young child
(>6months) with developmental or regression and/or newly 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 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 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 behavioral 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) |