In other species: Mallard , crab-eating macaque , dog , domestic ferret , horse , pig , taurine cattle , goat , sheep , peach-faced lovebird

Categories: Lysosomal storage disease , Nervous system phene

Mendelian trait/disorder: unknown

Disease-related: yes

Cross-species summary: The neuronal ceroid lipofuscinoses (NCLs) are a heterogenous group of inherited neurodegenerative diseases characterised by brain and retinal atrophy and the accumulation of autofluorescent lipopigment in neurons and many other cells within the body. Clinical features of NCL are abnormal behavior, dementia, loss of vision, motor disturbances and seizures, and premature death. See also gene specific entries including OMIA:001504 (PPT1-related), OMIA:001472 (TPP1-related), OMIA:002432 (CLN3-related), OMIA:001482 (CLN5-related), OMIA:001443 (CLN6-related), OMIA:001962 (CLN7/MFSD8-related), OMIA:001506 (CLN8-related), OMIA:001505 (CTSD10-related) and OMIA:001552 (ATP13A2-related).

Species-specific name: neuronal ceroid lipofuscinosis

Species-specific symbol: NCL

Species-specific description: There are several publications describing the naturally occuring feline NCL: 2 independent cases identified in domestic short haired cats (Weissenböck and Rössel 1997 and Bildfell et al. 1995), 1 in a Japanese domestic cat (Nakayama et al. 1993) and 2 unrelated Siamese cats (Green and Little 1974). In all cases, clinical signs and pathology findings were characteristic of NCL. Weissenböck and Rössel 1997 identified subunit c of mitochondrial ATP synthase as the storage material, a protein recognised as the main component of the storage material in most NCLs. Parentage and genetic background of the affected cats were unknown; therefore, mode of inheritance could not be established. However, the studies suggested an autosomal recessive mode of inheritance. None of the feline NCLs have been characterised on a molecular level.

Clinical features: Clinical onset varied between 7 months and 2 years of age. In all cases, NCL affected cats were presented with various neurological signs such as convulsion, uncoordinated gait, seizures and altered mentation. Several generalized signs were observed including hind leg weakness and behavioural changes such as mania and less alertness. Reduced visual perception was seen in 2 of the domestic cats with 1 cat progressing to complete blindness (Bildfell et al.. 1995) and another cat's eyesight severely reduced within weeks of onset (Weissenböck and Rössel 1997). The 3 domestic cats showed a progressively deteriorating state and were euthanized within months (Nakayama et al. 1993, Bildfell et al. 1995) or weeks (Weissenböck and Rössel 1997) of clinical onset. The Siamese cat died within a month of clinical onset due to severe convulsion that led to a comatose state and death (Green and Little 1974).

Pathology: Gross examination revealed marked atrophy of the brain, particularly of the cerebral hemispheres, with moderate enlargement of the lateral ventricles (Weissenböck and Rössel 1997, Nakayama et al. 1993). No gross abnormality was observed in the other 2 cases. Nakayama et al. (1993) reported brown discolouration with presence of nodulus on the liver and spleen surface. In all cases, multiple eosinophilic cytoplasmic storage bodies of various sizes were reported in neurons throughout the brain and spinal cord. Only the Japanese domestic cat showed additional storage materials in liver, spleen and lymph nodes (Nakayama et al. 1993). The storage bodies stained deep blue with Luxol fast blue (LFB), black with Sudan black B (SB), pink with Periodic acid Schiff (PAS) and emitted yellowish green autofluorescence under fluorescent microscopy. Fluorescence was not mentioned in the Siamese cats (Green and Little 1974). Only 1 case reported a diffuse retinal degeneration (Bildfell et al. 1995) even though 2 cats were reported to show a progressive visual deterioration (Weissenböck and Rössel 1997 and Bildfell et al. 1995). Differences were found in the ultrastructure of the storage material. In the Siamese cat it was described as "interwoven pattern with straight and curved elements" (Green and Little 1974), the material in the domestic cats was membrane bound and multilamellar (Bildfell et al. 1995, Weissenböck and Rössel 1997), whereas Nakayama et al. (1993) reported aggregates of electron dense granular materials. Immunohistochemistry (IHC) demonstrated storage of subunit c of mitochondrial ATP synthase (SCMAS) in the cytoplasm of many neurons of one domestic cat (Weissenböck and Rössel 1997). Nakayama et al. (1993) and Bildfell et al. (1995) did not characterise the storage material, however the ultrastructural profiles of the substance may suggest SCMAS.