Symptoma

Adult Neuronal Ceroid Lipofuscinosis

ANCL

Kufs disease is an inherited neurodegenerative disorder known as adult neuronal ceroid lipofuscinosis (ANCL). It is caused by the accumulation of lipopigments in the nerve cells resulting in progressive atrophy of certain regions of the brain characterized by cognitive and motor deficits.

Symptoms of Kufs disease may onset anywhere between adolescence and adulthood. However, signs and symptoms typically onset about 30 years of age. Common presenting features include ataxia, myoclonus, parkinsonism, chorea, spasticity, and cognitive impairment.

There are two subtypes of Kufs disease: Type A and Type B [1]. The symptoms of the subtypes often overlap and make it difficult to make a distinction between the two subtypes of Kufs disease [2] [3]. Regardless of the subtype, symptoms are progressive and worsen over time.

  • Short Stature

    However, in these conditions, one would expect ragged red fibers within muscle, elevated CSF protein, external ophthalmoplegia, short stature, and hearing loss. These features were not present in our patients. [onlinelibrary.wiley.com]

  • Spastic Paralysis

    Kufs, German psychiatrist, 1871-1955 an adult form of hereditary cerebral sphingolipidosis (amaurotic familial idiocy) characterized by cerebromacular degeneration, hypertonicity, and progressive spastic paralysis. [medical-dictionary.thefreedictionary.com]

    Kufs Disease: Description, Causes and Risk Factors: Any one of a group of inherited diseases characterized by failure to thrive, hypertonicity, progressive spastic paralysis, loss of vision and occurrence of blindness, usually with macular degeneration [medigoo.com]

  • Apraxia

    In her 30s, the patient developed cognitive impairment, ideomotor apraxia, cerebellar dysarthria and inappropriate laughter. Her sight was spared. [bmcneurol.biomedcentral.com]

  • Truncal Ataxia

    ataxia as well as a similar age of onset. [kufs-disease.wikia.com]

  • Monotonous Speech

    Case reports Index case On neurologic examination, this 30‐year‐old right‐handed man had a mini‐mental status examination (MMSE) of 29 out of 30, mild dysarthria, with low‐volume and monotonal speech, mild tremor of the hands, and occasional myoclonic [onlinelibrary.wiley.com]

  • Shuffling Gait

    Parkinsonism occurred a few years after disease onset, with stooped posture, shuffling gait, bradykinesia, and mask face. Four subjects deteriorated to a state of severe handicap, with severe dementia, contractures, dysphagia, and dysarthria. [onlinelibrary.wiley.com]

The diagnosis of Kufs disease is based on the recognition of symptoms, a patient and family history, psychiatric evaluation, clinical testing including a neurologic exam and specialized tests (e.g., enzyme assays and molecular genetic tests). Since Kufs disease is inherited, the patient should be asked about family members who may have had similar symptoms.

Enzyme assays can be useful for making a diagnosis. For example, Kufs disease is characterized by reduced enzyme activity of certain substances such as cathepsin F, the enzyme produced by the CTSF gene [7]. Recent studies have shown an association between certain enzyme defects and 8 primary genetic forms of Kufs disease [8].

Microscopic exam (using an electron microscope) of skin or tissue biopsies may show the buildup of storage material within the affected tissue. Lipopigment inclusions, while most frequently described in neuron cytoplasm, have also been found in vascular smooth muscle cells, Schwann cells and sweat gland epithelial cells. In Kufs disease, the deposits display a fingerprint-type pattern [9].

Molecular genetic testing permits a diagnosis of Kufs disease. It can reveal mutations in genes known to cause the various subtypes (e.g., CLN/CLN13 or PPT1 genes). It is important to note that a lack of mutations in these genes does not exclude the diagnosis of the disease since Kufs disease may be a result of genetic mutations in other, undocumented or unknown, genes [10].

An electroencephalogram can be used to examine the frequency and type of epileptic seizures.

Magnetic resonance imaging (MRI) scan may facilitate diagnosis of Kufs disease. During the early stages of behavioral changes associated with the disease, MRI images show hyperintensities in the white matter that indicate volume reduction of the corpus callosum [10].

Treatment: There is no cure for Kufs. Treatment is limited to reducing or controlling the symptoms of this disorder. Neurologists can assist in keeping seizures or nervous system complications under control. [medigoo.com]

TREATMENT There is no treatment to cure or slow down the progression of Kufs disease. Anticonvulsive drugs are helpful to control seizures and myoclonic jerking. [secure.ssa.gov]

Written by an international collection of authorities in the field, it provides invaluable advice on their diagnosis, patient care, and new treatments that are available. [books.google.ro]

One important symptoms that can distinguish the two is eye problems, in that there is decreased eye movements and whereas in Kufs the eyes are uneffected. [15] Also, HD is caused by having two copies of the Huntington gene. [15] Treatment and Prognosis [kufs-disease.wikia.com]

Prognosis Affected children suffer increasing mental impairment, worsening seizures, and progressive loss of sight and motor skills. Eventually, children with Batten disease become blind, bedridden and demented. [brainfoundation.org.au]

Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Diagnostic Criteria History and Symptoms Because vision loss is often an early sign, Batten disease/NCL may be first suspected during an eye exam. [wikidoc.org]

They are organised into groups, and further divided into clinical, etiological or histopathological sub-types. [orpha.net]

[…] in the case with late infantile neuronal ceroid lipofuscinoses: The sleep record shows generalized synchronous high-amplitude spike wave discharges recurring at an interval of 1–6 s Click here to view Neuronal ceroid lipofuscinoses (NCL) is a common etiology [neurologyindia.com]

Further research is needed to elucidate the genes and proteins involved in the etiology of this type of adult‐onset neuronal ceroid lipofuscinosis. [onlinelibrary.wiley.com]

A second report has also located this disease to this gene. [3] As you can see in the picture there is only a 25% chance that the child would contract the disease if each parent had one copy of the recessive mutation of the PPT gene Epidemiology Edit [kufs-disease.wikia.com]

Página 67 - Socioeconomic characteristics of childhood seizure disorders in the New Haven area: an epidemiologic study ‎ Página 67 - Epilepsy after penetrating head injury. I. Clinical correlates: a report of the Vietnam Head Injury Study. [books.google.es]

Fig. 1 Types of neuronal ceroid lipofuscinosis Kufs Disease (Type A and B); Oct 2012 Neuronal Ceroid Lipofuscinosis; Sep 2013 Neuronal Ceroid Lipofuscinosis; Jan 2014 Epidemiology Collectively, all forms of NCL affect an estimated 1 in 100.000 individuals [flipper.diff.org]

No References No Citations No Supplementary Data No Article Media No Metrics Keywords: NCL epidemiology ; NCL genes ; NCL pathogenesis ; NCL pathology ; NCL phenotypes ; NCL treatments Document Type: Research Article Publication date: 01 September 2014 [ingentaconnect.com]

Causes Differentiating Neuronal ceroid lipofuscinosis from Other Diseases Epidemiology and Demographics Batten disease /NCL is relatively rare, occurring in an estimated 2 to 4 of every 100,000 births in the United States. [wikidoc.org]

Identification of other protein constituents of the storage material could provide useful insights into the pathophysiology of disease and the natural substrates for TPP1. [biochemj.org]

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Neuronal ceroid lipofuscinoses (NCLs) are a subset of lysosomal storage diseases that involve defective cellular processing of [mayomedicallaboratories.com]

There were 14 cases where pathophysiological findings suggested LINCL but the specimens had detectable pepinase activity and there were no mutations found. [clinchem.aaccjnls.org]

Pathophysiology Genetics Childhood NCLs are autosomal recessive disorders; that is, they occur only when a child inherits two copies of the defective gene, one from each parent. [wikidoc.org]

Medical Therapy Surgery Primary Prevention Secondary Prevention References v t e Metabolic pathology / Inborn error of metabolism ( E70-90, 270-279 ) Amino acid Aromatic ( Phenylketonuria, Alkaptonuria, Ochronosis, Tyrosinemia, Albinism, Histidinemia [wikidoc.org]

However, these treatments did not prevent the fatal outcome of the disease. Prognosis Affected children suffer increasing mental impairment, worsening seizures, and progressive loss of sight and motor skills. [brainfoundation.org.au]

We know the cause, can pinpoint the gene but there is no preventative vaccine and once diagnosed premature death is the inevitable outcome. [medic8.com]

Fernandez-Chacon R, Wolfel M, Nishimune H, Tabares L, Schmitz F, et al. (2004) The synaptic vesicle protein CSP-alpha prevents presynaptic degeneration. Neuron 42: 237–251. View Article Google Scholar [journals.plos.org]

  1. Wisniewski KE, Kida E, Golabek AA, Kaczmarski W, Connell F. Neuronal Ceroid Lipofuscinoses: Classification and diagnosis. Advances in Genetics 45:1-33
  2. Martin JJ, Gottlob I, Goebel HH, Mole SE (1999) CLN 4. Adult NCL. In The Neuronal Ceroid Lipofuscinosis (Batten Disease). Goebel, H.H et al (ed.) Amsterdam: IOS Press (Publishers),2001; 77-90.
  3. Burneo J.G., Arnold T, Palmer CA, Kuzniecky R I, Oh S J, Faught E. Adult-onset Neuronal Ceroid Lipofuscinosis (Kufs Disease) with Autosomal Dominant Inheritance in Alabama, Epilepsia. 2003; 44:841-846.
  4. Sadzot B, Reznik M, Arrese-Estrada JE, Franck G. Familial Kufs' disease presenting as a progressive myoclonic epilepsy. J Neurol. 2000;247:447-54.
  5. Smith KR, Dahl HH, Canafoglia L, et al. Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis. Hum Mol Genet. 2013;22:1417-23.
  6. Velinov M, Dolzhanskaya N, Gonzalez M, et al. Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a proportion of cases: study of the Parry family and 8 other families. PLoS One. 2012;7:e29729.
  7. Arsov T, Smith KR, Damiano J, et al. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am J Hum Genet. 2011;88:566-73.
  8. Haltia M. The neuronal ceroid-lipofuscinoses. J Neuropathol Exp Neurol. 2003; 62:1-13.
  9. Lewandowska E, Lipczyńska-Łojkowska W, Modzelewska J, et al. Kufs’ disease: diagnostic difficulties in the examination of extracerebral biopsies. Folia Neuropathol 2009; 47: 259-67.
  10. Di Fabio R, Colonnese C, Santorelli FM, Pestillo L, Pierelli F. Brain imaging in Kufs disease type B: case reports. BMC Neurol. 2015;15:102.