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

Categories: Lysosomal storage disease , Nervous system phene

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: 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: Neuronal ceroid lipofuscinoses have been described in several sheep breeds (South Hampshire, Rambouillet, Swedish Landrace and Merino sheep). CONCL in Swedish Landrace sheep with congenital onset is distinct to OCL (ovine ceroid lipofuscinose) in South Hampshire, Rambouillet and Merino sheep where first clinical signs occur at about four to eight month of age. [Imke Tammen: 21 Jan 2002]. Likely causal variants have been identified in Swedish Landrace sheep (see OMIA:001505-9940 : Neuronal ceroid lipofuscinosis, 10 in Ovis aries); in Merino and South Hamsphire sheep (see OMIA:001443-9940 : Neuronal ceroid lipofuscinosis, 6 in Ovis aries) and in Borderdale sheep (see OMIA:001482-9940 : Neuronal ceroid lipofuscinosis, 5 in Ovis aries). Genetically engineered CLN1 sheep with a variant in the PPT1 have been created (see OMIA:001504-9940).

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

Clinical features: Affected newborn lambs are weak, trembling, and unable to rise and support their body. Those who are able to support their head and suckle will only survive a few weeks with bottle feeding. [Imke Tammen: 21 Jan 2002]

Pathology: At autopsy, the brain of affected lambs is about halve the normal size. Histological studies of the brain show granular storage material in the cytoplasm of neurons, neuronal loss, reactive astrocytosis and infiltration of macrophages. Smaller amounts of similar storage material can be found in 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. Electron microscopy reveals granular osmiophilic deposits (GRODs) in the neuronal storage bodies. Immunohistochemical studies show that the storage material consists mainly of sphingoloipid activator proteins (SAPs) A and D. In sheep with OCL the predominant storage material is mitochondrial ATP synthase subunit c. [Imke Tammen: 21 Jan 2002]

Breed: Rambouillet (Sheep) (VBO_0001570).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below