Characterization of Neuronal Ceroid-Lipofuscinosis in 3 Cats

Abstract

Three young domestic shorthair cats were presented for necropsy with similar histories of slowly progressive visual dysfunction and neurologic deficits. Macroscopic examination of each cat revealed cerebral and cerebellar atrophy, dilated lateral ventricles, and slight brown discoloration of the gray matter. Histologically, there was bilateral loss of neurons within the limbic, motor, somatosensory, visual, and, to a lesser extent, vestibular systems with extensive astrogliosis in the affected regions of all 3 cases. Many remaining neurons and glial cells throughout the entire central nervous system were distended by pale yellow to eosinophilic, autofluorescent cytoplasmic inclusions with ultrastructural appearances typical of neuronal ceroid-lipofuscinoses (NCLs). Differences in clinical presentation and neurological lesions suggest that the 3 cats may have had different variants of NCL. Molecular genetic characterization in the 1 cat from which DNA was available did not reveal any plausible diseasecausing mutations of the CLN1 (PPT1), CLN3, CLN5, CLN8, and CLN10 (CTSD) genes. Further investigations will be required to identify the mutations responsible for NCLs in cats.

A major facilitator superfamily domain 8 frameshift variant in a cat with suspected neuronal ceroid lipofuscinosis

“…Although not pathognomonic for the disease, the identification on MRI of cerebral and cerebellar atrophy with widened cerebral sulci, cerebellar folia, and increased volume in the ventricular system further increases the antemortem suspicion. Similar clinical and imaging findings have been reported in cats . Because the clinical signs and the imaging findings can overlap with other lysosomal storage diseases, identification of accumulation of autofluorescent ceroid storage material in neurological tissues is required for confirmation .…”

“…The clinical features of 8 cats with NCL confirmed by histopathology have been reported since 1974 . Domestic shorthair (7/9) cats and Siamese (2/9) are the 2 reported breeds.…”

“…The NCLs also have been reported in dogs but only rarely in cats . So far, causative genetic variants in dogs are known for CLN1, 2, 5, 6, 7, 8, 10, and 12, whereas none have been reported in cats.…”

Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions

“…Most forms of NCL are autosomal recessive in inheritance. In addition to affecting people, NCL-like disorders have been reported to occur naturally in a number of other mammalian species including dogs, cats, cattle, horses, sheep, mice, and monkeys, as well as in some non-mammalian species (Bildfell et al, 1995; Bond et al, 2013; Broom et al, 1998; Cesta et al, 2006; Chalkley et al, 2014; Evans et al, 2012; Fiske and Storts, 1988; Frugier et al, 2008; Gao et al, 2002; Green and Little, 1974; Hafner et al, 2005; Houweling et al, 2006; Jasty et al, 1984; Jolly et al, 1994a; Jolly and Palmer, 1995; Kay Read and Bridges, 1969; Nakayama et al, 1993; Nibe et al, 2011; Ranta et al, 1999; Reece and MacWhirter, 1988; Tammen et al, 2006; Tyynela et al, 2000; Url et al, 2001; Weissenbock and Rossel, 1997; Wheeler et al, 2002; Woods et al, 1993). Mouse, pig, fish, and insect models of the NCLs have also been created through genetic engineering (Bond et al, 2013; Bouchelion et al, 2014; Faller et al, 2015; Miller et al, 2015; Schultheis et al, 2013).…”

Neuronal Ceroid Lipofuscinosis in a Domestic Cat Associated with a DNA Sequence Variant That Creates a Premature Stop Codon inCLN6

“…The neuronal ceroid lipofuscinoses (NCLs) are hereditary progressive neurological diseases that occur in humans and a number of animal species including dogs, cats, sheep, and cattle ( Nakayama et al 1993 ; Bildfell et al 1995 ; Jolly 1995 ; Weissenböck and Rossel 1997 ; Houweling et al 2006 ; Tammen et al 2006 ; Frugier et al 2008 ; Kuwamura et al 2009 ; Mole et al 2011 ; Chalkley et al 2014 ; Katz et al 2017 ). These disorders are characterized by apparently normal development followed by progressive declines in cognitive and motor functions, visual impairment, seizures, and in most cases culminate in premature death.…”