Kufs disease is one of many diseases categorized under a disorder known as

neuronal ceroid lipofuscinosis Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments ( lipofuscin) in the body's tissues. These ...

(NCLs). NCLs are broadly described to create problems with vision, movement and cognitive function. Among all NCLs diseases, Kufs is the only one that does not affect vision, and although this is a distinguishing factor of Kufs, NCLs are typically differentiated by the age at which they appear in a patient

Signs and symptoms

Kufs is a neuronal disease, meaning it affects the nervous system, specifically voluntary movement and intellectual function. Symptoms of Kufs can manifest anytime between adolescence and adulthood, however it usually appears around age 30. There are two types of Kufs: Type A and Type B. Type A causes

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

myoclonic epilepsy Myoclonic epilepsy refers to a family of epilepsies that present with myoclonus. It starts in both sides of the body at once, and last for more than a second or two. When myoclonic jerks are occasionally associated with abnormal brain wave activit ...

(muscle jerks),

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

(compromised muscle coordination), tremors and tics,

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effective ...

(speech difficulties), confusion, and psychotic behaviour. Although similar to Type A, patients with Type B do not experience myoclonic epilepsy or dysarthria, and they do display changes in personality. It is occasional that patients present with skin disorders causing dryness, roughness, and scaliness. The skin symptoms specifically, are a result of

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up Scale (anatomy), scales, hair, Nail ...

buildup in the skin cells (see ‘Genetic causes’ for more information). Regardless of the type, most Kufs patients do not survive more than 15 years after their symptoms have manifested.

Genetics

Type A and Type B Kufs disease are caused by mutations in two sets of different genes. Both gene sets are responsible for producing proteins and

enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...

that are heavily involved in protein degradation and excretion in the cell – specifically, the nerve cell.

Type A

Mutations to the CLN6 and PPT1 genes result in Kufs disease Type A. CLN6 produces proteins that facilitate fat transport throughout a cell, as well as excretion out of the cell. The PPT1 gene codes for the enzyme palmotoyl-protein thioesterase-1. This enzyme is responsible for removing the fatty-acid side chains off of proteins that have been translocated into the

lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...

. By removing the surrounding fats, palmotoyl-protein thioesterase-1 creates easier access for other enzymes to break down the rest of the protein. Fatty substance build up in the brain is a consequence of the mutated genes. The fats and proteins that build up are called lipopigments. Eventually the buildup of lipopigments results in death of the neuron cells, giving way to the phenotypic symptoms. Type A is an

autosomal recessive In genetics, dominance is the phenomenon of one variant ( allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant an ...

disease, indicating that it is inherited from the parents. Each parent must carry one copy of the mutation; however, the recessive designation indicates that with only one copy, the parents are not affected, and do not show any symptoms.

Type B

Kufs disease Type B is caused by mutations to the DNAJC5 and CTSF genes. This form of Kufs is

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

, meaning that only one copy of each mutated gene is enough for the disease to manifest. When there is a mutation in the DNAJC5 gene, it affects the production of a cysteine string protein (CSP) that is coded within DNAJC5. CSP aids in transmitting signals through the nerves found in the brain. When the CTSF gene is mutated, it cannot produce Cathepsin F an enzyme that cuts proteins in the lysozyme. By cutting proteins, Cathepsin F can modify the function of the proteins as well as help break them down. Similar to Type A, when both DNAJC5 and CTSF are non-functional, it results in the incomplete breakdown of proteins. Once again, lipopigments build up and brain function is decreased as the neuron cells die.

Diagnosis

Diagnosis is usually done by performing genetic analysis (e.g. Sequencing, Genotyping) when there is reason to suspect Kufs disease. Clinicians may order such tests when the common phenotypes of Kufs disease are observed in patients in order to confirm the diagnosis.

Treatment

Supportive care is the manner in which this condition is managed

References

External links

{{Medical resources , ICD10 = E75.4 , ICD9 = , ICDO = , OMIM = 162350 , OMIM_mult = {{OMIM, 204300, , none {{OMIM, 256730, , none {{OMIM, 601780, , none {{OMIM, 610127, , none {{OMIM, 614706, , none {{OMIM, 615362, , none , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = C537950 , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 79262 Rare diseases Neurodegenerative disorders