Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience
Abstract Background Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodege...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-01-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-021-02162-z |
| _version_ | 1819006858183049216 |
|---|---|
| author | R. Badilla-Porras A. Echeverri-McCandless J. M. Weimer A. Ulate-Campos A. Soto-Rodríguez A. Gutiérrez-Mata L. Hernández-Con S. Bogantes-Ledezma A. Balmaceda-Meza J. Brudvig A. Sanabria-Castro |
| author_facet | R. Badilla-Porras A. Echeverri-McCandless J. M. Weimer A. Ulate-Campos A. Soto-Rodríguez A. Gutiérrez-Mata L. Hernández-Con S. Bogantes-Ledezma A. Balmaceda-Meza J. Brudvig A. Sanabria-Castro |
| author_sort | R. Badilla-Porras |
| collection | DOAJ |
| description | Abstract Background Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population. Objective To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations. Methods DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants’ sociodemographic and clinical characteristics were also obtained from their medical records. Results Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens. Conclusions This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies. |
| first_indexed | 2024-12-21T00:15:21Z |
| format | Article |
| id | doaj.art-149f6e5ef7d8453fbcc750d90deb2354 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-21T00:15:21Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-149f6e5ef7d8453fbcc750d90deb23542022-12-21T19:22:15ZengBMCOrphanet Journal of Rare Diseases1750-11722022-01-011711910.1186/s13023-021-02162-zNeuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experienceR. Badilla-Porras0A. Echeverri-McCandless1J. M. Weimer2A. Ulate-Campos3A. Soto-Rodríguez4A. Gutiérrez-Mata5L. Hernández-Con6S. Bogantes-Ledezma7A. Balmaceda-Meza8J. Brudvig9A. Sanabria-Castro10Clinical Genetic and Metabolism Department, National Children’s Hospital, CCSSResearch Unit, Hospital San Juan de Dios, CCSSPediatrics and Rare Diseases Group, Sanford ResearchNeurology Department, National Children’s Hospital, CCSSResearch Unit, Hospital San Juan de Dios, CCSSNeurology Department, National Children’s Hospital, CCSSNeurology Department, National Children’s Hospital, CCSSNeurology Department, National Children’s Hospital, CCSSCENDEISSS, CCSSPediatrics and Rare Diseases Group, Sanford ResearchResearch Unit, Hospital San Juan de Dios, CCSSAbstract Background Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population. Objective To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations. Methods DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants’ sociodemographic and clinical characteristics were also obtained from their medical records. Results Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens. Conclusions This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.https://doi.org/10.1186/s13023-021-02162-zNeuronal ceroid lipofuscinosisBatten diseaseCNL6Variant late infantile NCLvLINCLLysosomal storage disease |
| spellingShingle | R. Badilla-Porras A. Echeverri-McCandless J. M. Weimer A. Ulate-Campos A. Soto-Rodríguez A. Gutiérrez-Mata L. Hernández-Con S. Bogantes-Ledezma A. Balmaceda-Meza J. Brudvig A. Sanabria-Castro Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience Orphanet Journal of Rare Diseases Neuronal ceroid lipofuscinosis Batten disease CNL6 Variant late infantile NCL vLINCL Lysosomal storage disease |
| title | Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience |
| title_full | Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience |
| title_fullStr | Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience |
| title_full_unstemmed | Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience |
| title_short | Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience |
| title_sort | neuronal ceroid lipofuscinosis type 6 cln6 clinical findings and molecular diagnosis costa rica s experience |
| topic | Neuronal ceroid lipofuscinosis Batten disease CNL6 Variant late infantile NCL vLINCL Lysosomal storage disease |
| url | https://doi.org/10.1186/s13023-021-02162-z |
| work_keys_str_mv | AT rbadillaporras neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT aecheverrimccandless neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT jmweimer neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT aulatecampos neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT asotorodriguez neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT agutierrezmata neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT lhernandezcon neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT sbogantesledezma neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT abalmacedameza neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT jbrudvig neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience AT asanabriacastro neuronalceroidlipofuscinosistype6cln6clinicalfindingsandmoleculardiagnosiscostaricasexperience |