Schulz et al. (2004) described a ninth variant of juvenile-onset neuronal ceroid lipofuscinosis in 2 Serbian sisters and 2 German brothers. The sisters, whose great-grandmothers came from adjacent villages, developed declining vision, progressive ataxia, and seizures by age ... Schulz et al. (2004) described a ninth variant of juvenile-onset neuronal ceroid lipofuscinosis in 2 Serbian sisters and 2 German brothers. The sisters, whose great-grandmothers came from adjacent villages, developed declining vision, progressive ataxia, and seizures by age 4 years. By age 10 years, they could not walk independently and became mute. The 2 brothers showed a similar course as the sisters, presenting at age 4 years with declining vision and seizures. Cognitive decline was apparent at age 6 years, ataxia and rigidity occurred at age 9 years, and they were mute by age 12 years. The younger brother died at age 15 years following pneumonia, and the older brother, who later had hallucinations and dysphagia, died at age 19 years. All patients had slowed EEGs with polyspike wave discharges. Laboratory studies in 1 of the brothers showed neurons ballooned with autofluorescent fine granular material. A brain biopsy from 1 sister showed neurons with granular and curvilinear bodies. Fibroblasts from all patients were small and rounded with prominent nucleoli, attached poorly, and were highly apoptotic. They showed increased DNA synthesis and increased expression of several cyclins. Patient fibroblasts also showed a decrease in ceramide, sphingomyelin, lactosylceramide, ceramide trihexoside, and globoside, indicating a perturbation of sphingolipid metabolism. Enzyme screening and genetic testing ruled out other NCL types and lysosomal storage disorders. Schulz et al. (2006) found that fibroblasts derived from patients with neuronal ceroid lipofuscinosis-9 showed markedly decreased levels of dihydroceramide and decreased dihydroceramide synthase activity. The cells showed partial correction of growth defects and apoptosis when transfected with CLN8 (607837) and several human LASS genes (see, e.g., LASS1; 606919), all of which increase dihydroceramide synthase activity. Schulz et al. (2006) concluded that the CLN9 protein may be a regulator of dihydroceramide synthase.