Table 2.
Diagnostic algorithm for NCL diseases.
| Clinical presentation | Necessary diagnostic | 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 standstill or regression and/or newly occurring severe epilepsy of unknown cause | Enzyme testing for PPT1 and TPP1 (dry blood spots or leucocytes or fibroblasts) | |
| PPT1 deficient: | CLN1 | |
| TPP1 deficient: | CLN2 | |
| If PPT1 and TPP1 enzyme activities are normal: Electron microscopic examination (skin biopsy or lymphocytes). | ||
| If storage material is present: genetic testing. | CLN5, CLN6, CLN7, CLN8, CLN14 | |
| School child with visual loss and/or dementia and epilepsy | Search for lymphocyte vacuoles (light microscopy of blood smear, Fig. 2). | |
| If lymphocyte vacuoles are present: | 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 activities are normal: Electron microscopic examination (skin biopsy or lymphocytes). | ||
| If storage material is present: | CLN5, CLN6, CLN7, CLN8, CLN12 | |
| 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 | |
| CTSF deficient: | CLN13 | |
| If enzyme activities are 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 If autosomal recessive: CLN6, CLN11, CLN13 |