Kufs disease is a very rare neurodegenerative disorder that mainly affects the nervous system. The main symptoms of this progressive condition are problems with motor skills and cognitive decline, although a range of other symptoms are possible. The serious disease usually occurs in people between the ages of thirty and forty. The life expectancy of these patients is shortened. The disease is also known as “mature/adult neuronal ceroid lipofuscinosis” or “CLN4”.
- Epidemiology of Kufs disease
- Types
- Causes and heredity of adult neuronal ceroid lipofuscinosis
- Symptoms of motor skills (muscles) and nervous system (brain)
- Diagnosis and examinations
- Treatment of neurodegenerative disease
- Prognosis of Kufs disease
Epidemiology of Kufs disease
Kufs disease is a condition that falls under a group of disorders: neuronal ceroid lipofuscinoses (NCLs). These conditions affect the nervous system and usually lead to progressive problems with vision, motor skills (movement) and thinking skills. The different types of NCLs are distinguished by the age at which the signs and symptoms first appear. The incidence of all forms of NCL is estimated at 100,000 people worldwide. NCLs are more common in Finland and Sweden, where about 1 in 12,500 people have the condition. Kufs disease represents approximately 1.3-10 percent of NCLs.
Types
Two types of Kufs disease have been described, namely type A and type B. They have a different genetic cause and a different pattern of inheritance, and the symptoms also differ. Type A is characterized by a combination of seizures and uncontrollable muscle twitches (myoclonic epilepsy), a decrease in intellectual function (dementia), reduced muscle coordination (the medical term for this is “ataxia”), involuntary movements such as tremors or tics and speech problems (dysarthria ). Type B shares many features with type A, but is characterized by personality changes and is not associated with myoclonic epilepsy or dysarthria.
Causes and heredity of adult neuronal ceroid lipofuscinosis
Genetic change
Sometimes the cause of Kufs disease is unknown. But sometimes the cause lies in a gene mutation. A mutation (change) in the CLN6 or PPT1 gene leads to the disease type Kufs A, and a mutation in the DNAJC5 or CTSF gene results in the disease type Kufs B. In Kufs disease, the body of a patient with the mutated gene is unable to break down long-chain fatty acids (lipofuscins). This results in an accumulation of excess substances and pigments in the body.
Inheritance pattern
Kufs disease type A has an autosomal recessive inheritance pattern. In an autosomal recessive inheritance, both copies of the gene in each cell have the mutations. The parents of a patient with an autosomal recessive disorder each carry one copy of the mutated gene, but they usually show no symptoms of the condition. Kufs disease type B has an autosomal dominant inheritance pattern. With autosomal dominant inheritance, one copy of the mutated gene in each cell is enough to cause the condition. Most cases of Kufs disease type B occur in people with no family history.
Symptoms of motor skills (muscles) and nervous system (brain)
Symptoms of Kufs disease usually appear between the ages of thirty and forty, but they can develop any time between adolescence and late adulthood. The symptoms of Kufs disease worsen as the patient ages. When the disease occurs, affected patients survive an average of fifteen years.
Muscles
The progressive metabolic disease is characterized by reduced muscle coordination, epileptic seizures, rapid involuntary jerky movements (chorea), and rarely blindness occurs. Patients’ vision often remains intact with this condition. Epilepsy is usually the first syndrome to present.
Brain and nerves
The neurological symptoms of Kufs disease usually begin after the age of twenty and this then resembles a psychological disorder. The patient exhibits confusion and psychotic behavior. These symptoms lead to intellectual disability and generalized convulsions (convulsions: uncontrollable physical movements and changes in consciousness). Excess pigment in fat (lipofuscins) that accumulates in the brains of patients with Kufs disease is the cause of the symptoms.
Skin
In addition, some patients present with dry and rough skin. This occurs as a result of overproduction and/or retention of keratin (the main component of the skin).
Diagnosis and examinations
The diagnosis is often difficult, partly because the symptoms are very variable. The patient is sometimes initially diagnosed with a mental illness or early dementia. The diagnosis is made through a clinical examination in which the doctor looks at the history and examines the patient physically and neurologically. Clinical findings include myoclonus, ataxia, parkinsonism (some symptoms of Parkinson’s disease and other neurological symptoms), chorea, spasticity and cognitive impairment. The doctor may perform a genetic test to detect gene mutations, although this is not required for the diagnosis.
Treatment of neurodegenerative disease
There is no proven effective treatment available. Therefore, treatment is mainly symptomatic and supportive. Antiepileptic drugs help to reduce epileptic seizures. It is also best for a patient to follow physiotherapy, occupational therapy and speech therapy to continue to use the body’s functions for as long as possible. Furthermore, psychotherapy is indicated, also for the environment.
Prognosis of Kufs disease
The age at which affected patients die is variable. However, the life expectancy of someone suffering from Kufs disease is shortened.
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