Correspondence

Case 27-2002: Late-Onset Infantile Neuronal Ceroid Lipofuscinosis

N Engl J Med 2003; 348:2159May 22, 2003

Article

To the Editor:

Rust and Karluk (Aug. 29 issue)1 discuss the case of a child with a neurodegenerative disorder who was found to have curvilinear lysosomal inclusion bodies on electron-micrographic analysis of a muscle-biopsy specimen. Late-onset infantile neuronal ceroid lipofuscinosis was diagnosed. The approach to confirming this diagnosis is puzzling.

The authors mention that subsequent molecular testing for the two common mutations of CLN2 failed to identify a mutation, but no enzyme testing was performed. Given that only 66 percent of patients with a clinical diagnosis of late-onset infantile neuronal ceroid lipofuscinosis are found to have mutations in CLN2, 2 a more prudent approach would have been first to document enzyme deficiency of tripeptidyl-peptidase I (TPP-I), the protein product of CLN2. DNA-based testing for CLN2 could then be performed in order to document any deficiency. Molecular testing of CLN1 and CLN3 could be performed if enzyme sufficiency was demonstrated, since mutations in these genes have been identified in patients with a clinical diagnosis of late-onset infantile neuronal ceroid lipofuscinosis.3 Clinical features of CLN6 and CLN7 (the Gypsy–Indian and Turkish variants, respectively) are not easily distinguishable from those of CLN2; testing is available for mutations in these two genes. If mutational testing is performed first, a negative result unfortunately leaves one in the position of not knowing whether the right gene has been found (although the mutation cannot be located) or whether the wrong gene is being studied. Initial enzyme testing can obviate this problem.

Kim L. McBride, M.D.
Baylor College of Medicine, Houston, TX 77030
kimm@bcm.tmc.edu

3 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 27-2002). N Engl J Med 2002;347:672-680
   Full Text | Web of Science | Medline

2. 2

   Zhong NA, Wisniewski KE, Ju W, et al. Molecular diagnosis of and carrier screening for the neuronal ceroid lipofuscinoses. Genet Test 2000;4:243-248
   CrossRef | Web of Science | Medline

3. 3

   Zhong N, Moroziewicz DN, Ju W, et al. Heterogeneity of late-infantile neuronal ceroid lipofuscinosis. Genet Med 2000;2:312-318
   CrossRef | Web of Science | Medline

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