Niemann-Pick disease

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Niemann-Pick disease

Niemann-Pick disease (pronounced ne'mahn pik) refers to a group of fatal inherited metabolic disorders that are included in the larger family of lysosomal storage disease

Lysosomal storage disease

Lysosomal storage diseases are a group of approximately 40 rare inherited metabolic disorders that result from defects in lysosome function. Lysosomal storage diseases result when a specific organelle in the body's cells ? the lysosome ? malfunctions....
s (LSDs).

ann-Pick diseases are classified in a subgroup of LSDs called sphingolipidoses

Sphingolipidoses

Sphingolipidoses are a class of disorders relating to Sphingolipid metabolism....
or lipid storage disorder

Lipid storage disorder

Lipid storage disorders are a group of inherited metabolism disorders in which harmful amounts of lipids accumulate in some of the body?s cell s and tissues....
s in which harmful quantities of a fatty substances, called lipid

Lipid

Lipids are broadly defined as any fat-soluble , naturally-occurring molecule, such as fats, oils, waxes, cholesterol, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others....
s, accumulate in the spleen

Spleen

The spleen is an organ found in all vertebrate animals. In humans, the spleen is located in the abdomen of the body, where it functions in the destruction of redundant red blood cells, and holds a reservoir of blood....
, liver

Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
, lung

Lung

The lung is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart....
s, bone marrow

Bone marrow

Bone marrow is the flexible biological tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells....
, and brain

Brain

The brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as cnidarian and echinoderm have a decentralized nervous system without a brain, while sponges lack any nervous system at all....
. Histology demonstrates lipid laden macrophages in the marrow, as well as "sea-blue histiocytes" on pathology.

toms are related to the organs in which they accumulate.

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Encyclopedia

Niemann-Pick disease (pronounced ne'mahn pik) refers to a group of fatal inherited metabolic disorders that are included in the larger family of lysosomal storage disease

Lysosomal storage disease

Pathophysiology

Niemann-Pick diseases are classified in a subgroup of LSDs called sphingolipidoses

Sphingolipidoses

Sphingolipidoses are a class of disorders relating to Sphingolipid metabolism....
or lipid storage disorder

Lipid storage disorder

Lipid

Spleen

Liver

Lung

Bone marrow

Bone marrow is the flexible biological tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells....
, and brain

Brain

Presentation

Symptoms are related to the organs in which they accumulate. Enlargement of the liver and spleen (hepatosplenomegaly

Hepatosplenomegaly

Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis or can be the sign of a serious and life threatening lysosomal storage disease....
) may cause reduced appetite, abdominal distension and pain as well as thrombocytopenia

Thrombocytopenia

Thrombocytopenia is the presence of relatively few platelets in blood.Generally speaking, in humans, a normal platelet count ranges from 150,000 and 450,000 per mm3....
secondary to splenomegaly.

Sphingomyelinase accumulation in the central nervous system

Central nervous system

The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of multicellular organisms....
(including the cerebellum

Cerebellum

The cerebellum is a region of the brain that plays an important role in the integration of perception, coordination and motoneuron control. In order to coordinate motor control, there are many neural pathways linking the cerebellum with the cerebrum motor cortex and the spinocerebellar tract ....
) results in unsteady gait (ataxia

Ataxia

Ataxia is a neurology sign and symptom consisting of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of parts of the nervous system that coordinate movement, such as the cerebellum....
), slurring of speech (dysarthria

Dysarthria

Dysarthria is a motor speech disorder resulting from Brain damage, characterised by poor articulation . Any of the speech subsystems can be affected....
) and discoordinated swallowing (dysphagia

Dysphagia

Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right....
). Basal ganglia

Basal ganglia

The basal ganglia are a group of Nucleus in the brain interconnected with the cerebral cortex, thalamus and brainstem. Mammalian basal ganglia are associated with a variety of functions: motor control, cognition, emotions, and learning....
dysfunction causes abnormal posturing of the limbs, trunk and face (dystonia

Dystonia

Dystonia is a neurology movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be Heredity or caused by other factors such as Birth trauma or other physical trauma, infection, poisoning or reaction to Medication....
) and upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy). More widespread disease involving the cerebral cortex

Cerebral cortex

The cerebral cortex is a structure within the brain that plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness....
and subcortical structures is responsible for gradual loss of intellectual abilities causing dementia

Dementia

Dementia is the progressive decline in cognition due to damage or disease in the body beyond what might be expected from normal aging. Although dementia is far more common in the geriatric population, it may occur in any stage of adulthood....
and seizure

Seizure

An epileptic seizure is a transient symptom of abnormal, excessive or synchronous neuronal activity in the brain. It can manifest as an alteration in mental state, tonic or clonic movements, convulsions, and various other psychic symptoms ....
s.

Sleep related disorders are also seen, including gelastic cataplexy

Cataplexy

Cataplexy is a medical condition which often affects people who have narcolepsy, a disorder whose principal signsare EDS , sleep attacks, sleep paralysis, Hypnagogia and disturbed night-time sleep....
(sudden loss of muscle tone associated with laughter), and sleep inversion (sleepiness during the day and wakefulness at night).

Treatment

No specific treatment is available for Niemann-Pick with care being mostly supportive. Anecdotally, organ transplant has been attempted with limited success. Future prospects include enzyme replacement and gene therapy. There is variable severity of presentation seen with patients in the most severe subtypes having an average life expectancy of two years. bone marrow transplant has been attempted for type B. C & D are usually on a low cholesterol diet. supportive care through nutrition, medication, physical therapy and being followed by specialists can help with quality of life.

History

Albert Niemann

Albert Niemann (paediatrician)

Albert Niemann was a German physican.Niemann-Pick disease is named for him and Ludwig Pick.He was the son of the Albert Niemann ....
published the first description of what is now known as Niemann-Pick disease, type A, in 1914. Luddwick Pick described the pathology of the disease in a series of papers in the 1930s.

Genetics

Mutations in the SMPD1 gene

Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
cause Niemann-Pick disease types A and B, and mutations in NPC1

NPC1

Niemann-Pick disease, type C1 also known as NPC1 is a protein which in humans is encoded by the NPC1 gene.NPC1 was identified as the gene that when mutated, results in Niemann-Pick disease, type C....
and NPC2

NPC2

NPC2 is a protein associated with Niemann-Pick disease, type C.External links...
cause Niemann-Pick disease, type C

Niemann-Pick disease, type C

Niemann-Pick type C is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. Niemann-Pick Type C strikes an estimated 1:150,000 people....
(NPC). Type D was originally separated from Type C to delineate a group of patients with otherwise identical disorders who shared a common Nova Scotian ancestry. Patients in this group are now known to share a specific mutation in the NPC 1 gene, and NPC is now used to embrace both groups. The terms "Niemann-Pick type I" and "Niemann-Pick type II" were proposed to separate the high and low sphingomyelin forms of the disease in the early 1980s, before the molecular defects were described.

Niemann-Pick disease is inherited in an autosomal recessive pattern, which means both copies, or allele

Allele

An allele is one member of a pair or series of different forms of a gene. Usually alleles are coding region, but sometimes the term is used to refer to a junk DNA....
s, of the gene must be mutated (altered in such a way that function is impaired, in contrast to a polymorphism

Polymorphism

In general, polymorphism describes multiple possible states for a single property .Polymorphism may specifically refer to:In the biological sciences...
, in which the nucleotide

Nucleotide

Nucleotides are molecules that comprise the structural units of RNA and DNA. Additionally, nucleotides play central roles in metabolism. In that capacity, they serve as sources of chemical energy , participate in cell signaling , and are incorporated into important cofactors of enzymatic reactions ....
sequence is altered but causes no functional disruption) for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene. If both parents are carriers, there is a 25% chance with each pregnancy for an affected child. Genetic counseling

Genetic counseling

Genetic counseling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning in order to prevent, avoid or ameliorate it....
and genetic testing

Genetic testing

Genetic testing allows the Genetics diagnosis of vulnerabilities to inherit diseases, and can also be used to determine a person's ancestry. Normally, every person carries two copies of every gene, one inherited from their mother, one inherited from their father....
is recommended for families who may be carriers of Niemann-Pick.

Classification

In 1961, the following classification was introduced:

Niemann-Pick disease type A: classic infantile
Niemann-Pick disease type B: visceral
Niemann-Pick disease, type C
Niemann-Pick disease, type C

Niemann-Pick type C is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. Niemann-Pick Type C strikes an estimated 1:150,000 people....
: subacute/juvenile
Niemann-Pick disease type D: Nova Scotian

Now that the genetics are better understood, the condition can be classified as follows:

Niemann-Pick disease, SMPD1-associated
Niemann-Pick disease, SMPD1-associated

Niemann-Pick disease, SMPD1-associated refers to two different types of Niemann-Pick disease which are associated with the SMPD1 gene.There are approximately 1,200 cases of NPA and NPB worldwide with the majority of cases being Type B or an intermediate form....
, which includes types A and B

Niemann-Pick disease, type C
Niemann-Pick disease, type C

Niemann-Pick type C is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. Niemann-Pick Type C strikes an estimated 1:150,000 people....
, which includes types C1 and C2. (Type D is caused by the same gene as type C1.)