Abstract
Secondary cerebral folate deficiency (CFD) has been described in various neurodegenerative
diseases, for example, Aicardi–Goutieres syndrome, Kearns–Sayre syndrome, and other
mitochondriopathies. The importance of associated CFD lies in the possibility that
treatment with folinic acid may improve the outcome of these diseases, or its presence
may affect the course of the disease. We describe a patient with neuronal ceroid lipofuscinosis
(NCL) type 2 due to tripeptidyl-peptidase I (TPP1) deficiency with an atypical presentation
of chorea and dystonia. She was subsequently found to have low cerebrospinal fluid
(CSF) 5-methyltetrahydrofolate (5-MTHF). TPP1 level in skin fibroblast cultures was < 0.1
nmol/min/mg protein (normal range: 0.7–2.2 nmol/min/mg protein), confirming the diagnosis
of NCL. CSF 5-MTHF was 36 nmol/L (normal range: 40–150 nmol/L) while red blood cell
folate was slightly elevated at 1,902 nmol/L (normal range: 776–1,784 nmol/L). Oral
folinic acid was administered with no clear amelioration of the movement disorder.
This is the first documented case of low CSF folate levels in NCL. Given the unusual
clinical presentation of dyskinesia, it is possible that low CSF 5-MTHF levels may
have contributed to this. It is important to evaluate CSF 5-MTHF levels in patients
with NCL as low cerebral folate levels may aggravate the neurodegenerative process.
Keywords
neuronal ceroid lipofuscinosis - methyltetrahydrofolate - folate deficiency
