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

Categories: Lysosomal storage disease , Nervous system phene

Links to MONDO diseases: No links.

Mendelian trait/disorder: unknown

Considered a defect: 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 is only 1 report of NCL in equines to date, with 3 distantly related horses of an Austrian stud in cross-breds of Icelandic horse and Peruvian paso (Url et al 2001). All three horses showed developmental retardation, slow movements and loss of appetite at the age of six months; followed by an onset of neurological symptoms that steadily progressed from the age of 1 year. The horses condition deteriorated, and was euthanized 1� years after clinical onset. Macroscopic examination of the brain revealed slight flattening of the gyri in all 3 horses, with yellow-brownish discoloration observed in the brain of 2 horses (Url et al 2001). Microscopically, all 3 horses showed massive loss of neurons of all cortical layers of the cerebrum and a striking astrocytosis. An eosinophilic autofluorescence storage material was found mainly in neurons in the cerebral cortex and with less frequency in neurons of other brain regions, spinal cord, retina and submucous and myenteric ganglia. The storage material stained deep blue with Luxol-fast blue, (LFB) Nile blue A (NBA) and to a lesser degree, pink with periodic acid-Schiff (PAS) and black with Sudan black (SB). Immunohistochemistry (IHC) revealed large amounts of subunit c of mitochondrial ATP synthase (SCMAS) and small amounts of saponins (SAPs) storage bodies. Electron microscopy (EM) of the tissue samples revealed markedly enlarged lysosomes containing material arranged in fingerprint, curvilinear and rectilinear ultrastructural patterns. NCL in horses is suggested to be autosomal recessively inherited (Url et al 2001).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: All three horses showed developmental retardation, slow movements and loss of appetite at the age of six months (Url et al. 2001). This was followed by an onset of neurological symptoms at the age of 1 year; with characteristics of torticollis, ataxia, head tilt and visual failure (observed in 1 horse). The neurological disorders progressed, and the horses condition deteriorated. Affected horses have a reduced lifespan.

Pathology: Macroscopic examination of the brain revealed slight flattening of the gyri in all 3 horses, with yellow-brownish discoloration observed in the brain of 2 horses (Url et al 2001). No atrophy of retinal layers was observed. Microscopically, all 3 horses showed massive loss of neurons of all cortical layers of the cerebrum and a striking astrocytosis. An eosinophilic, autofluorescence storage material was found mainly in neurons in the cerebral cortex and with less frequency in neurons of other brain regions, spinal cord, retina and submucous and myenteric ganglia. The storage material stained deep blue with Luxol-fast blue, (LFB) Nile blue A (NBA) and to a lesser degree, pink with periodic acid-Schiff (PAS) and black with Sudan black (SB). Immunohistochemistry (IHC) using antiserum against subunit c of mitochondrial ATP synthase (SCMAS) revealed strong, granular immunostaining in neurons of brain and spinal cord of all horses, with some present in retinal neurons of 1 horse. IHC also revealed small amounts of saponins (SAPs) storage bodies. IHC results were positive for extraneural SCMAS and both neuronal and extraneural SAPs in tissues of control horses, but that is presumably due to certain equine tissues that physiologically contain a relatively high level of SCMAS and SAPs. Electron microscopy (EM) of the tissues sample revealed markedly enlarged neuronal lysosomes containing material arranged in fingerprint and rectilinear ultrastructural patterns. Storage material was also found in lysosomes of kidney tubular cells, and in lymphocytes and macrophages of lymph nodes; with the lamellar profiles for lymph nodes storage bodies revealing rectilinear and curvilinear formations (Url et al 2001).