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

Categories: Lysosomal storage disease , Nervous system phene

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: no

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 description: In cattle, neuronal ceroid lipofuscinosis has been described in an inbreed herd of Beefmaster cattle in 1969 in the USA and in a herd of Devon cattle in Australia in 1988. The disease is characterised predominantly by blindness and behavioural changes. The clinical signs and the pathological findings are similar in both breeds, with less detailed records for the Beefmaster cattle. Nevertheless, NCL in Beefmaster and Devon cattle could represent different variants of this heterogenous group of diseases. In comparison to NCL in other species, brain atrophy in Devon cattle appears to be less severe and affected animals reach older ages (>9 years). A likely disease causing variant has been identified in Devon cattle: OMIA:001482-9913 : Neuronal ceroid lipofuscinosis, 5 in Bos taurus. [Imke Tammen: 21 Jan 2002]

Clinical features: Affected Beefmaster and Devon cattle are born normal and develop progressive blindness at an age of 9-14 month. When disturbed, they tend to walk or trot in circles and may show a mild head tilt. The affected Beefmaster reported by Read and Bridges (1969) became comatose interrupted by periodic clonic convulsions only six month after onset of disease. Affected Devon cattle are reported to die of misadventures but can live up to at least 9 years of age in a save environment. [Imke Tammen: 21 Jan 2002]

Pathology: At necropsy, brains of affected Devon cattle show mild atrophy and yellow brown discolouration. Histological findings include severe retinal atrophy (nearly complete loss of rods and cones) and mild atrophy of the brain with infiltration of macrophages and astrocytosis. Intracytoplasmic accumulation of storage material can be found in neurons and many extraneural cell types. The storage material can be strongly stained by luxol fast blue, PAS and Sudan black B methods and shows autofluorescence in ultraviolet light. The predominant component of the storage material was identified by amino acid sequencing and mass spectroscopy to be mitochondrial ATP synthase subunit c (Martinus et al. 1991). [Imke Tammen: 21 Jan 2002]