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 . The symptoms of the subtypes often overlap and make it difficult to make a distinction between the two subtypes of Kufs disease  . Regardless of the subtype, symptoms are progressive and worsen over time.
- Type A disease is characterized by progressive, worsening seizures and muscle contractions (myoclonus). Some affected individuals also have difficulty coordinating voluntary movements (ataxia). Other signs and symptoms of Type A include tics, tremors, dysarthria (speech difficulties), confusion, dementia, and/or psychotic behavior.
- Symptoms of Type B disease are similar to those of Type A. However, in most cases, patients exhibit personality changes and facial tics. Other symptoms such as myoclonic epilepsy (seizures) or dysarthria occur less commonly than in Type A   .
Entire Body System
- Progressive Dementia
Firstly, their clinical presentation can mimic several other rare causes of progressive myoclonic epilepsy or dementia with motor deterioration. [jnnp.bmj.com]
Showing of 11 | 80%-99% of people have these symptoms Abnormal pyramidal sign 0007256 Abnormality of extrapyramidal motor function 0002071 Ataxia 0001251 Dementia Dementia, progressive Progressive dementia [ more ] 0000726 Generalized myoclonic seizures [rarediseases.info.nih.gov]
Kufs disease is a disorder presenting with rather non-specific features of progressive neurodegeneration including seizures, psychiatric manifestations and progressive dementia. [journals.plos.org]
- Visual Impairment
Patients with Batten disease suffer progressive neurological impairment because of their damaged cells. Symptoms like visual impairment and seizures are among the difficulties they will face. [bdsra.org]
Visual loss occurs but is not obvious because of profound cognitive impairment. [omicsonline.org]
She had never experienced visual impairment or shown electroretinographic abnormalities. [karger.com]
They currently comprise 14 genetically distinct disorders, mostly characterized by progressive cognitive, motor, and visual impairment with onset in childhood, adolescence, and even adulthood. [medlink.com]
Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients. Mol Genet Metab. 2019;126(2):188-95. doi: 10.1016/j.ymgme.2018.12.001. [ Links ] 3. [scielo.org.co]
- Psychiatric Symptoms
Patients presented at onset (31 and 38 years), with psychiatric symptoms only. At present (ages 56 and 54 years), visual, verbal, and cognitive losses have progressed and both patients have cerebellar ataxia and cannot walk without support. [onlinelibrary.wiley.com]
Psychiatric symptoms of children and adolescents with juvenile neuronal ceroid lipofuscinosis. J Intellect Disabil Res. 2005 Jan;49(Pt1):25-32. Boehme DH, Cottrell JC, Leonberg SC, et al. A dominant form of neuronal ceroid-lipofuscinosis. [beyondbatten.org]
Please note, if the patient’s primary presentation symptom is epilepsy but other NCL symptoms such as visual decline, behavioral/psychiatric symptoms, motor disturbances, or others are not present, consider choosing the Invitae epilepsy panel instead, [invitae.com]
- Psychiatric Manifestation
Secondly, psychiatric manifestations may be the first presentation in DNAJC5 positive individuals. The proband of the Parry family presented with such manifestations long before other symptoms were noted. [journals.plos.org]
Other symptoms such as myoclonic epilepsy (seizures) or dysarthria occur less commonly than in Type A. [symptoma.com]
Kufs type A presents with seizures, myoclonus (abrupt spasms), ataxia (loss of coordination of the muscles), dementia, and dysarthria (difficulties with articulation). [secure.ssa.gov]
Type A causes seizures, myoclonic epilepsy (muscle jerks), dementia, ataxia (compromised muscle coordination), tremors and tics, dysarthria (speech difficulties), confusion, and psychotic behaviour. [en.wikipedia.org]
Type B: Type B is not associated with epilepsy or dysarthria; however, as with Kufs disease type A, its characteristic features include dementia, ataxia, tics and tremors. [medigoo.com]
- Cerebellar Ataxia
At present (ages 56 and 54 years), visual, verbal, and cognitive losses have progressed and both patients have cerebellar ataxia and cannot walk without support. [onlinelibrary.wiley.com]
ataxia, bulbar symptoms, and extrapyramidal and pyramidal signs, but without retinal lesions and rapidly progressive dementia. [icd10data.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 . Recent studies have shown an association between certain enzyme defects and 8 primary genetic forms of Kufs disease .
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 .
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 .
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 .
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]
Innovative treatments led to some results in mouse models related to lysosome hydrolase defects. [ingentaconnect.com]
Food and Drug Administration today approved Brineura (cerliponase alfa) as a treatment for a specific form of Batten disease. Brineura is the first FDA-approved treatment to slow loss of... [evidence.nhs.uk]
There are no disease-specific treatments for ANCL yet. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]
What is the prognosis for an individual with Neuronal Ceroid Lipofuscinosis, CLN6-related? The prognosis for individuals with NCL, CLN6-related disorders is poor. [myriad.com]
Unfortunately, the long-term outlook ( prognosis ) for people with adult neuronal ceroid lipofuscinosis is generally poor. The symptoms tend to become worse over time, resulting in a shortened life expectancy. [rarediseases.info.nih.gov]
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]
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.  Also, HD is caused by having two copies of the Huntington gene.  Treatment and Prognosis [kufs-disease.wikia.com]
[…] with early deaths while juvenile and adult onset forms have a relatively better prognosis. [annalsofian.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]
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]
A second report has also located this disease to this gene.  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]
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]
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]
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]
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]
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]
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]
Typical clinical, ophthalmoscopic, EEG, and neuroimaging features can be suggestive of this rare disease preventing misdiagnosis, thus helping in genetic counseling. Axillary skin biopsy is of immense utility for diagnostic confirmation. 1. Zhong N. [annalsofian.org]
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]
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- 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.
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- 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.