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.

• 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 [4] [5] [6].

• 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]

• Inappropriate Laughter

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

• Visual Hallucination

  Progressive dementia and psychotic symptoms as well as auditory and visual hallucinations and delusions emerged, causing anxiety. [kufs-disease.wikia.com]

• Denial

  Your lawyer will work with you each step of the way and if you do need to appeal a denial, your attorney will ensure that your appeal is given priority status under the Compassionate Allowances guidelines. [disabilitybenefitscenter.org]

• 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].

• Generalized Polyspikes

  Ictal recordings captured myoclonic jerks simultaneous with generalized polyspike and wave activity, followed by 1–2 s of attenuation of the background. EEG in bipolar montage. [onlinelibrary.wiley.com]

• Multifocal Spikes

  EEGs were abnormal in all patients, showing generalized and multifocal spikes and polyspikes. No abnormal responses to photic stimulation were found. [onlinelibrary.wiley.com]

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