The Newfoundland aggregate of neuronal ceroid-lipofuscinosis

Publisher Website
Google Scholar
Abstract
We have found a group of individuals with the late infantile, the early juvenile variant, and juvenile neuronal ceroid-lipofuscinosis (NCL) in Newfoundland, an island with a population of 500,000. In the past 25 yr, we have ascertained 44 cases of NCL in 32 sibships: 32 cases of late infantile NCL (LINCL) in 24 sibships, 11 cases of the early juvenile variant in 7 sibships, and one patient with the juvenile form (JNCL). The clinical presentation of the LINCL patients is very characteristic, with onset of seizures at age 2½ to 3½ yr, frequently with drop attacks and myoclonic jerks, followed by mental deterioration, ataxia, visual loss, and death by the end of the first decade. Typical curvilinear profiles are seen on electron microscopy (EM). The second group of patients mainly have the early juvenile variant with onset of seizures at age 5 to 6 yr and fingerprint profiles with occasional curvilinear profiles on EM. However, a child with the juvenile form presenting with blindness was also encountered. In both of these types, death occurs in the second decade of life. There is no overlap of these three clinical forms within sibships, although both late infantile and early juvenile variant types may occur in the same small fishing village. All three forms appear to be inherited as autosomal recessive traits. Although the early juvenile variant has been postulated to represent a double heterozygote between LINCL and JNCL, this cannot be confirmed on the basis of the present study. Most patients originate form small isolated fishing communities of Anglo-Saxon origin on the south and east coasts of Newfoundland, some of which can still be reached only by water. Based on the number of new patients born in Newfoundland (1 to 2 NCL cases per yr), the birth rate, and the population size, the heterozygote frequency is estimated at approximately 1 in 30. Although accurate diagnosis and genetic counseling have decreased or eliminated families with multiple cases, carrier detection is still a great need in this population.