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Juvenile neuronal ceroid lipofuscinosis: clinical course and genetic studies in Spanish patients

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Background

Juvenile neuronal ceroid lipofuscinosis (JNCL, NCL3, Batten disease) is usually caused by a 1.02-kb deletion in the CLN3 gene. Mutations in the CLN1 gene may be associated with a variant form of JNCL (vJNCL). We report the clinical course and molecular studies in 24 patients with JNCL collected from 1975 to 2010 with the aim of assessing the natural history of the disorder and phenotype/genotype correlations.

Patients and methods

Patients were classified into the groups of vJNCL with mutations in the CLN1 gene and/or granular osmiophilic deposit (GROD) inclusion bodies (n = 11) and classic JNCL (cJNCL) with mutations in the CLN3 gene and/or fingerprint (FP) profiles (n = 13). Psychomotor impairment included regression of acquired skills, cognitive decline, and clinical manifestations of the disease. We used Kaplan-Meier analyses to estimate the age of onset of psychomotor impairment.

Results

Patients with vJNCL showed learning delay at an earlier age (median 4 years, 95% confidence interval [CI] 3.1–4.8) than those in the cJNCL group (median 8 years, 95% CI 6.2–9.7) (P = 0.001) and regression of acquired skills at a younger age. Patients with vJNCL showed a more severe and progressive clinical course than those with cJNCL. There may be a Gypsy ancestry for V181L missense mutation in the CLN1 gene.

Conclusions

The rate of disease progression may be useful to diagnose vJNCL or cJNCL, which should be confirmed by molecular studies in CLN1/CLN3 genes. Further studies of genotype/phenotype correlation will be helpful for understanding the pathogenesis of this disease.

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Acknowledgments

We are indebted to Drs Armstrong, Vernet, Vilaseca, Coll and Gort, and the families of the patients for the valuable support and indispensable cooperation, and Dr Marta Pulido for editing the manuscript and editorial assistance (medical editing services were provided on behalf of the authors).

Funding

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Author information

Authors and Affiliations

  1. Departments of Pediatric Neurology and Clinical Biochemistry and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Hospital de Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain

    María-Socorro Pérez-Poyato, Raquel Montero Sánchez & Mercè Pineda Marfà

  2. Biochemical and Molecular Genetics Department and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain

    Montserrat Milà Recansens & Laia Rodríguez-Revenga

  3. IDIBAPS, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain

    Montserrat Milà Recansens

  4. Department of Pathology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

    Isidre Ferrer Abizanda

  5. Department of Pathology, Hospital de Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain

    Victoria Cusí Sánchez

  6. Unit of Pediatric Neurology, Hospital de Figueres, Girona, Spain

    M. Mar García González

  7. Unit of Pediatric Neurology, Hospital Virgen de la Arrixaca, Murcia, Spain

    Rosario Domingo Jiménez

  8. Unit of Pediatric Neurology, Hospital Reina Sofía, Córdoba, Spain

    Rafael Camino León

  9. Service of Pediatric Neurology, Hospital La Paz, Madrid, Spain

    Ramón Velázquez Fragua & Antonio Martínez-Bermejo

  10. Department of Pediatric Neurology, Hospital Sant Joan de Déu, Passeig de Sant Joan de Déu 2, E-08950 Esplugues de Llobregat, Barcelona, Spain

    Mercè Pineda Marfà

Authors
  1. María-Socorro Pérez-Poyato
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  2. Montserrat Milà Recansens
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  3. Isidre Ferrer Abizanda
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  4. Raquel Montero Sánchez
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  5. Laia Rodríguez-Revenga
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  6. Victoria Cusí Sánchez
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  7. M. Mar García González
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  8. Rosario Domingo Jiménez
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  9. Rafael Camino León
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  10. Ramón Velázquez Fragua
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  11. Antonio Martínez-Bermejo
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  12. Mercè Pineda Marfà
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Corresponding author

Correspondence to Mercè Pineda Marfà.

Additional information

Communicated by: Sedel Frederic

Competing interest: None declared.

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Pérez-Poyato, MS., Milà Recansens, M., Ferrer Abizanda, I. et al. Juvenile neuronal ceroid lipofuscinosis: clinical course and genetic studies in Spanish patients. J Inherit Metab Dis 34, 1083–1093 (2011). https://doi.org/10.1007/s10545-011-9323-7

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  • DOI: https://doi.org/10.1007/s10545-011-9323-7

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