Spino-cerebellar degeneration with polyneuropathy associated with ceroid lipofuscinosis in one family.
There are several clinically distinct forms of neuronal ceroid lipofuscinosis whose presentation and pathology are usually homogeneous within families. Several atypical variants have also been reported. We have studied an inbred sibship in which neuronal ceroid lipofuscinosis appeared to present in two completely different ways. In the proband, the course was compatible with a somewhat atypical juvenile variant. Ataxia and spasticity started at 4.5 years, followed by blindness with optic atrophy, intractable seizures, dementia, and death at 14 years. Atypical features included areflexia, hypotonia, and ataxia. Electron microscopic studies of her skin and her rectal ganglion cells showed lucent, dense, and fingerprint inclusions that were also found in the central nervous system at autopsy. Her brother and sister developed difficulty walking at ages 8.5 and 10.5 years and are alive at 24 and 18 years. They presented with slowly progressive spinocerebellar degeneration with sensorimotor neuropathy without dementia, seizures, or visual impairment. Lysosomal enzymes and lipoprotein analysis were normal in all three siblings and their parents. Elevated dolichol in the urine and lucent, dense, and fingerprint inclusions in skin, cutaneous nerve, buffy coat lymphocytes in both siblings and in the sural nerve of the brother suggest that their disease may represent a novel phenotype of neuronal ceroid lipofuscinosis. While it is possible that two different recessive genes may be segregating in this consanguineous family, we cannot dismiss the possibility that variability of gene expression may account for the divergent phenotypes.
New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
K E
KE
Wisniewski
R E
RE
Madrid
M
M
Dambska
I
I
Rapin
R
R
Pullarkat
S
S
Sklower
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D003241:Consanguinity; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000648:ultrastructure; D010375:Pedigree; D010525:Peripheral Nerves / Q000473:pathology; D011115:Polyneuropathies / Q000235:genetics* / Q000473:pathology; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000473:pathology