A Family with Adult Type Ceroid Lipofuscinosis (Kufs' Disease) and Heart Muscle Disease: Report of Two Autopsy Cases.

Sakajiri, Kenichi; Matsubara, Nae; Nakajima, Takashi; Fukuhara, Nobuyoshi; Makifuchi, Takao; Wakabayashi, Masatoshi; Oyanagi, Shinsaku; Kominami, Eiki

doi:10.2169/internalmedicine.34.1158

Cited by 14 publications

(14 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[21][22][23][24] Results of preliminary studies have indicated that the storage bodies from the cerebella of affected Tibetan Terriers do not contain appreciable amounts of this protein. The mechanisms that underlie the accumulation of subunit c protein in some forms of CL are not known; therefore, the absence of large amounts of this protein in storage bodies from Tibetan Terriers does not rule out the possibility that the canine disease and one of the CLs in humans have a common genetic basis.…”

Section: Discussionmentioning

confidence: 99%

Assessment of retinal function and characterization of lysosomal storage body accumulation in the retinas and brains of Tibetan Terriers with ceroid-lipofuscinosis

Katz¹,

Narfström²,

Johnson³

et al. 2005

ajvr

View full text Add to dashboard Cite

Behavioral assessments of the affected dogs revealed moderate visual impairment in low-light conditions but good vision in bright light. On funduscopic evaluation of these dogs, abnormalities detected ranged from none to signs of moderately advanced retinal degeneration. Compared with findings in the control dog, electroretinography revealed depressed rod cell function with some impairment of cone cell function in the affected dogs. Morphologically, disease-specific storage bodies were detected in retinal Müller cells and neurons, particularly in ganglion cells, and in cells of the cerebral cortex and cerebellum in affected dogs. Substantial photoreceptor cell loss and disruption of photoreceptor outer segment morphology appeared to develop late in the disease. IMPLICATIONS FOR HUMAN MEDICINE: The similarities between ceroid-lipofuscinosis in Tibetan Terriers and some forms of ceroid-lipofuscinosis in humans suggest that the canine disease may have a genetic and biochemical basis similar to that of one of the ceroid-lipofuscinosis disorders in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Assessment of retinal function and characterization of lysosomal storage body accumulation in the retinas and brains of Tibetan Terriers with ceroid-lipofuscinosis

Katz¹,

Narfström²,

Johnson³

et al. 2005

ajvr

View full text Add to dashboard Cite

show abstract

“…Indeed, accumulation of lysosomal storage material occurs in many tissues and organs outside of the CNS in CLN2 disease and other NCLs both in both human patients 1, 11–14 and in canine models 4, 5, 15–18 . Progressive development of cardiac pathology has also been reported in at least some forms of NCL, including CLN2 19–22 . Once CSF administration of recombinant TPP1 or TPP1 gene therapy administered via the CSF is adopted as the treatment for CLN2 disease, it appears quite possible that when neurological signs are ameliorated by these treatments and survival is extended, pathology in other tissues and organs will become apparent.…”

Section: Introductionmentioning

confidence: 88%

Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression

et al. 2017

View full text Add to dashboard Cite

CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1 which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of lifespan. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function, and development of histopathological myocardial lesions. Progressive increases in plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system.

show abstract

“…These result from the accumulation of storage materials in the cardiac tissue and have been histopathologically confirmed in Pompe disease, mucopolysaccharidosis, Fabry disease, mucolipidosis, Gaucher disease, GM1/GM2 gangliosidosis, and juvenile and adult forms of NCL 12 . Cardiac complications have been reported in 21 cases of juvenile/adult NCL (Table I) and include ventricular hypertrophy, sinus bradycardia, atrial fibrillation, and supraventricular and ventricular tachycardia 4–8 . Conduction system abnormalities ( n =8) and repolarization disturbances ( n =6) have been observed on ECG in 19 examined individuals 4–8 .…”

Section: Discussionmentioning

confidence: 99%

“…The accumulation of these lipopigments is most abundant in neurons but can also be detected in almost all tissues, including the skin and heart 1 . This may be linked to the cardiomyopathic complications and conduction system abnormalities that are common in juvenile and adult NCLs 4–8 . Here we present the first case of LINCL that manifested with a progressive conduction block, eventually leading to cardiac death at 28 years of age.…”

mentioning

confidence: 89%

Progressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis

Fukumura

Saito

et al. 2011

Develop Med Child Neuro

View full text Add to dashboard Cite

LINCL Late infantile neuronal ceroid lipofuscinosis NCL Neuronal ceroid lipofuscinosisThis article reports the case of a female with late infantile neuronal ceroid lipofuscinosis who developed right and left anterior bundle branch blocks and episodic bradycardia at 23 years of age. Several episodes of supraventricular tachycardia manifested at 23 and 27 years of age. In addition, a transient second-degree atrioventricular conduction block also emerged at 27 years of age. Atrial fibrillation and aggravation of the atrioventricular conduction block resulted in progressive bradycardia and cardiac death at the age of 28 years. Cardiac involvement and accumulation of lipopigments in the myocardium and cardiac conduction system have been recognized in juvenile neuronal ceroid lipofuscinosis, but this is the first report to describe progressive conduction defects in a case of late infantile neuronal ceroid lipofuscinosis.

show abstract

A Family with Adult Type Ceroid Lipofuscinosis (Kufs' Disease) and Heart Muscle Disease: Report of Two Autopsy Cases.

Cited by 14 publications

References 12 publications

Assessment of retinal function and characterization of lysosomal storage body accumulation in the retinas and brains of Tibetan Terriers with ceroid-lipofuscinosis

Assessment of retinal function and characterization of lysosomal storage body accumulation in the retinas and brains of Tibetan Terriers with ceroid-lipofuscinosis

Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression

Progressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis

Contact Info

Product

Resources

About