The Newfoundland aggregate of neuronal ceroid-lipofuscinosis

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 2 1/2 to 3 1/2 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.(ABSTRACT TRUNCATED AT 250 WORDS)