Pre- and postnatal enzyme analysis for infantile, late infantile and adult neuronal ceroid lipofuscinosis (CLN1 and CLN2).
The recent development of simple, fluorogenic enzyme assays for infantile and late infantile neuronal ceroid lipofuscinosis (INCL and LINCL; CLN1 and CLN2) has greatly facilitated the diagnostic process for these diseases. In leucocytes and fibroblasts from INCL (n = 38) patients we found profound deficiencies of palmitoyl-protein thioesterase I (PPT1), the residual activity was < 5% of mean control activity. In fibroblasts from LINCL patients we found a similar deficiency of tripeptidyl-peptidase I activity (TPP-I), with < 2% activity in 16 patients. The residual TPP-I activity in leucocytes from LINCL patients seemed substantially higher. We also showed the feasibility of reliable prenatal enzyme analysis. In five first-trimester and two second-trimester prenatal analyses for INCL, four affected foetuses were detected (PPT activity 3-6%). Two first trimester pregnancies at risk for LINCL were analysed and a clear TPP-I deficiency was detected in both cases (TPP-I activity 3-4%). The first patient with adult neuronal ceroid lipofuscinosis (ANCL) due to a deficiency of PPT is presented; her present age is 53 years and the onset of the disease was at 38 years with psychiatric symptoms.
Van Diggelen
O P
OP
Department of Clinical Genetics, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands. vandiggelen@kgen.fgg.eur.nl
Keulemans
J L
JL
Kleijer
W J
WJ
Thobois
S
S
Tilikete
C
C
Voznyi
Y V
YV
D000328:Adult; D000626:Aminopeptidases; D002478:Cells, Cultured; D015193:Chorionic Villi Sampling; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008875:Middle Aged; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis* / Q000201:enzymology*; D011247:Pregnancy; D057057:Serine Proteases; D013869:Thiolester Hydrolases / Q000172:deficiency* / Q000378:metabolism; D000091346:Tripeptidyl-Peptidase 1
D000091346:Tripeptidyl-Peptidase 1; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase; D010450:Endopeptidases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human