Hereditary progressive neurodegenerative disorders
with mental retardation, visual loss (retinitis pigmentosa), and seizures. Neuronal ceroid
lipofuscinoses are probably the most common class of neurodegenerative
disease in children.
Four types of neuronal ceroid
lipofuscinoses are described in the literature. They are characterized by
intralysosomal accumulations of autofluorescent lipopigment in various
Type I: Infantile Neuronal Ceroid Lipofuscinosis (Finnish Infantile Neuronal Ceroid Lipofuscinosis Type; Infantile Neuronal
Ceroid Lipofuscinoses; Santavuori Disease; Santavuori-Haltia Disease).
Type II: Late Infantile Neuronal Ceroid Lipofuscinosis (Jansky-Bielschowsky Disease; Late Infantile Type of Amaurotic Idiocy; Late
Infantile Batten Disease): A few variants of this form of neuronal ceroid
lipofuscinosis are determined by the mutation on the gene map locus
15q21-q23. Three variants have been described: (A) neuronal ceroid lipofuscinosis variant 6, which corresponds to
mutations in the CLN6 gene; (B) Turkish neuronal ceroid lipofuscinosis variant 8 (also called northern progressive epilepsy
with mental retardation syndrome), which is caused by mutation in the CLN8
gene; and (C) Finnish neuronal ceroid lipofuscinosis variant 5, which is caused by mutation in the CLN5 gene.
Type III: Juvenile Neuronal Ceroid Lipofuscinosis (Infantile Batten Disease; Vogt-Spielmeyer Disease; Amaurotic Familial
Idiocy of the Juvenile Type): One genetic variant of the Batten juvenile
form of neuronal ceroid lipofuscinosis has been described and consists of
the presence of granular osmiophilic deposits (GROD) and the absence of
fingerprint curvilinear bodies. Clinically, these patients demonstrate
learning disabilities beginning at ages 6 and 10 years but visual failure is
delayed until age 14 years.
Type IV: Adult Neuronal Ceroid Lipofuscinosis (Kufs Disease; Autosomal Recessive Kufs Disease): Autosomal dominant form
has been described for the Kufs disease and is characterized by progressive
neurodegenerative diseases but absence of ocular involvement.
1:20,000 in the general population of Finland for early
infantile and juvenile forms to 1:150,000 in the general population.
All neuronal ceroid lipofuscinoses are
autosomal recessive and are genetically independent.
Precise pathogenesis and etiology of this group of
diseases are elusive. The common defect underlying all neuronal ceroid
lipofuscinoses affects lysosomal function characterized by intralysosomal
accumulation of an autofluorescent lipopigment in the perikaryon of
different neuronal cell types in granula, curvilinear, or fingerprint
patterns. Clinically, this results in a profound degenerative impact on the
central nervous system. In addition to the diseases outlined, numerous
atypical variants indicated in the classification of neuronal ceroid
lipofuscinoses account for approximately 10 to 20% of patients. Several
eponymous names are associated with these disorders, which are sometimes
collectively known as Batten disease.
Young patients with gradual onset of blindness and
neurologic signs, retinitis pigmentosa, and epilepsy should be examined for
neuronal ceroid lipofuscinosis. Urinary dolichol level is raised, and biopsy
of the skin or conjunctiva demonstrates characteristic lipofuscin storage.
The early juvenile form results in death within
the first decade of life. The later-onset forms are associated with dementia
and a slower decline.