Natural history of CLN6- disease in Argentina

PESAOLA FAVIO; CISMONDI INÉS ADRIANA; BECERRA ADRIANA; LEYES CLAUDIA; VENIER ANA CLARA; GUELBERT NORBERTO; NOHER INES

Congreso; NCL 2018 London; 2018

CLN6 disease is a type of Neuronal Ceroid Lipofuscinosiswith onset at late infantile / adult ages. The etiologicaldiagnosis may be delayed due to the overlappingphenotypical features with other NCL diseases. Thenatural history of this disease is poorly known and showsvariations of the clinical evolution around the World. ThreeArgentine individuals were clinically followed with theintegrated evaluation of the phenotypes / genotypes. Outof these, 2/3 was genotyped by successive PCR of genesand Sanger sequencing, and 1/3 was genotyped throughWES. Clinical time table: symptoms onset 2-3.3y withdecreased motor function; frequent falls 2-4.5y; assistedmarch 4.4-6.11y; total prostration 5.11-9.6y; language delay3.3-4y; speech difficulties 4.4-4.5y, speech loss 5.11-9.6y;visual loss 3-7y; blindness (only reported in 1/3 cases) 5y;refractory seizures with generalized atonic myoclonicmovements and lateralization of the trunk 3-5.9y; earlydeath: 1 / 3 15y, 1/3>18y 1/3 living with 10.3y. Electronmicroscopy of a skin biopsy: dense structure ceroidlipofuscin type bodies with fingerprint profiles combinedwith curvilinear bodies 2/3; curvilinear bodies 1/3. variantsof the CLN6 gene: Case 1, PCR + Sanger: E4c.486 + 8C>T / E7 c.755G> A; Case 2, PCR + Sanger: E4c.307 C> T /E6 c.556dupC; Case 3, WES: E4c.461_463delTCA / E3c.250T> A. Record of the lapse of time from the onset ofsymptoms to the etiological diagnoses: Case 1, 21.3y;Case, 2.8y; Case 3, 6.8y. Concluding remarks: the naturalhistory of the CLN6 disease was stated in 3 Argentinecases with late infantile onset ages. Seven DNA variantswere recognized in heterozygous combinations, out ofthese 5 were pathological, 1 probably pathological and 1without pathological significance. The time interval for theetiological diagnosis decreased ~ 75% integrating WESand the clinical characteristics. To further shorten thediagnostic time interval it is needed to develop asystematized WES screening methodology, or to find aspecific biomarker for this orphan disease. A fastendiagnosis is a necessity if a specific therapy will becomeavailable.