Differential natural history of late infantile CLN6 and CLN2 diseases of Neuronal Ceroid Lipofuscinoses

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

Congreso; SLEIMPN 2019; 2019

CLN6 and CLN2 diseases show onset ages at late infantile (LI) and adult (A) ages.CLN2 has also a juvenile or protracted form (1). The clinical course of LI-CLN6 andLI-CLN2 needs to be carefully differentiated to facilitate early diagnoses.OBJECTIVES: To point out the differences among the natural history of LI-CLN6and LI-CLN2 diseases. Three Argentine individuals suspected of a NCL wereevaluated under clinical, biochemical, morphological and genetic criteria. Other 27were formerly published as affected of CLN2 disease (1). The 3 CLN6 cases showedTPP1 values in the control´s range. Onset symptoms of LI-CLN2 cases were speechdelay or failure at 2-4y, and short after that seizures, visual failure, movementdisorder, early death. CLN6 cases showed symptoms onset at 2-3.3y withdecreased motor function; frequent falls 2-4.5y; assisted march 4.4-6.11y; totalprostration 5.11-9.6y; language delay 3.3-4y; speech difficulties 4.4-4.5y, speechloss 5.11-9.6y; visual loss 3-7y; blindness (only reported in 1/3 cases) 5y;refractory seizures with generalized atonic myoclonic movements andlateralization of the trunk 3-5.9y; early death: 1/3 15y, 1/3>18y 1/3 living at 10.3y.In the CLN6 disease the electron microscopy of skin biopsies showed densefingerprint profiles and some curvilinear bodies (CV). The LI-CLN2 skin morphologywas mostly CV. Genetic variants; CLN6: Case 1, E4c.486 + 8C> T / E7 c.755G> A;Case 2, E4c.307 C> T / E6 c.556dupC; Case 3, E4c.461_463delTCA/E3 c.250T>A.DNA variants in CLN2, as published (1). The natural history of LI-CLN6 disease wasstated in 3 Argentine cases and crucial differences with the LI-CLN2 disease werefound at clinical, morphological and biochemical levels. Clinically LI-CLN6 disease isan early movement disorder in contrast to CLN2 that initiates frequently withspeech delay or failure, followed by seizures. The suspicion of CLN6 disease can beemitted on the base of the movement disorder at onset and lacking TPP1deficiency. No A-CLN6 disease (Kufs) was recognized up to date in Argentina, thusa study of the differences with adult and juvenile CLN2 disease is pending. (1)Kohan R, Pesaola F, et al 2015. BBActa. 1852: 2301 -2311.