Hematopoietic stem cell transplantation in infantile neuronal ceroid lipofuscinosis.
OBJECTIVE
To study the effect of allogeneic hematopoietic stem cell transplantation (SCT) on the clinical course of infantile neuronal ceroid lipofuscinosis (INCL), a lysosomal storage disease.


BACKGROUND
INCL is a progressive encephalopathy with severe neuronal loss, especially in the cerebral and cerebellar cortex and retina. Autofluorescent lipopigments constitute the typical storage material in INCL. The disease is caused by recessive mutations in the palmitoyl protein thioesterase 1 (PPT1) gene. PPT1 is a depalmitoylating enzyme, which is transported to lysosomes through the mannose-6-phosphate receptor-mediated pathway, and participates in the lysosomal degradation of fatty acylated proteins.


METHODS
Three patients with INCL received transplants and were followed up after SCT at the Hospital for Children and Adolescents at the University of Helsinki. The first patient rejected the first graft at the age of 7 months and had mild symptoms of INCL at the second transplantation at 11 months. The two other patients were asymptomatic when they received their transplants at the age of 4 months.


RESULTS
PPT1 enzyme activity was normalized in peripheral leukocytes, but remained low in the CSF and resulted only in a mild and transient amelioration of the classic INCL. All patients who received transplants developed INCL by the age of 2 or 3 years.


CONCLUSIONS
More experimental animal and cell culture studies are needed to determine the in vivo function of PPT1. SCT currently cannot be recommended as therapy for INCL.
Lönnqvist
T
T
Hospital for Children and Adolescents, Department of Child Neurology, University of Helsinki, Finland. tuula.longqvist@hus.fi
Vanhanen
S L
SL
Vettenranta
K
K
Autti
T
T
Rapola
J
J
Santavuori
P
P
Saarinen-Pihkala
U M
UM
D002675:Child, Preschool; D005260:Female; D005312:Fetal Blood; D005387:Finland; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000628:therapy*; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics
D010170:Palmitoyl-CoA Hydrolase