Niemann-Pick disease types A and B (NORD)

Definitions & Key takeaways

Niemann-Pick disease (NPD) type A and type B, are rare inherited conditions characterized by the inability to break down sphingomyelin, due to a deficiency of the enzyme acid sphingomyelinase. Niemann-Pick disease type A and type B result from SMPD1 gene mutation, which normally encodes to sphingomyelinase enzyme.

NPD-A symptoms present early in life and may include hepatosplenomegaly, jaundice, feeding difficulties, and progressive loss of reflexes and muscle tone. It is also often associated with a cherry red spot � in the eye, which affects the macula and impairs central vision. Usually, NPD-A becomes fatal by the age of 3 years old.

On the other hand, NPD-B represents a less severe condition that typically does not include neurologic involvement, and can develop at any time in life. Common NPD-B symptoms include progressive splenomegaly, which causes low serum platelet and white blood cell levels, high cholesterol, and declining lung function. There is no cure for NPA and NPB, and treatment is supportive and focuses on managing symptoms.

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Niemann-Pick disease type A and type B, or NPD-A and NPD-B, which are subtypes of acid sphingomyelinase or ASM deficiency, are rare, genetically inherited conditions characterized by the inability to break down a fat called sphingomyelin due to a deficiency of the enzyme, acid sphingomyelinase.
There’s also Niemann-Pick disease type C, which is known to be caused by mutations in the genes NPC1 and NPC2, and is therefore considered to be distinct from types A and B.
Sphingomyelin is a fat that's included in the membrane of many different cells. When cells become old or damaged, they are often phagocytized, or eaten, by macrophages, which are cells of the immune system.
They contain organelles called lysosomes that are said to function as recycling centers because they break down large, potentially harmful substances to be reused by the body.
They break down sphingomyelin by using an enzyme called acid sphingomyelinase, which is a product of the sphingomyelin phosphodiesterase 1, or SMPD1 gene.
In Niemann-Pick disease types A and B, there’s a mutation in the SMPD1 gene that causes a defect in the production of sphingomyelinase, leading to an inability to break down sphingomyelin.
In NPD-A there’s almost a complete absence of sphingomyelinase activity, while NPD-B has some residual sphingomyelinase activity remaining.
While the mechanism isn’t completely understood, sphingomyelin primarily accumulates in the lysosomes of macrophages, which travel throughout the body and cause damage in multiple organs and tissues.
The macrophages develop a characteristic lipid-laden appearance under microscopes and are called “foam cells.” Sphingomyelin can also build up in other cell types in the body, reflecting impaired intracellular recycling of membranes and damaged organelles in lysosomes due to sphingomyelinase deficiency.Signs and symptoms of NPD-A present early in life, and are usually life-threatening.
These include enlargement of the liver and/or spleen, jaundice, feeding difficulties, and progressive loss of reflexes and muscle tone.
Infants also often develop a “cherry red spot” in the eye that affects the macula, which corresponds with a decrease in central vision.
This is thought to develop when excess material collects within the cells around the fovea, making them appear pale. Meanwhile, the fovea, which contains very few cells, remains its normal “cherry red” color.
Macrophages accumulate in the lungs and cause interstitial lung disease that can progress to respiratory failure. This form of the disease is often fatal by the age of three years old.
NPD-B represents a less severe condition that typically does not include neurologic involvement, and manifestations can develop at any time in life.
It may include any of the non-neurologic developments mentioned for NPD-A, and is generally characterized by progressive splenomegaly, which causes low serum platelet and white blood cell levels, high cholesterol, and declining lung function.
Some patients fall in the spectrum between types A and B, and are referred to as NPD type AB.Mutations in the SMPD1 gene are typically inherited in an autosomal recessive fashion, and while NPD-A occurs more often in individuals of the Ashkenazi Jewish lineage, NPD-B occurs in those of all ethnicities.
Diagnosis includes a clinical examination and history, blood tests to detect sphingomyelinase activity in white blood cells, and genetic testing to evaluate the SMPD1 gene.Treatment of NPC-A includes supportive therapy based on the symptoms that may include a feeding tube and medications to assist with sleeping.
NPC-B requires regular lab testing every 6-to-12 months, and appropriate supportive treatment for whichever manifestations develop.##SummaryAll right, as a quick recap....Niemann-Pick disease type A and type B are rare, inherited conditions characterized by the inability to break down sphingomyelin due to a deficiency of the enzyme acid sphingomyelinase.
In type A, the manifestations are typically fatal by the age of 3 years old, while type B is milder and can present at any time in life.
Diagnosis includes an examination, blood tests, and genetic testing, while treatment consists of supportive therapy. the age of three years old while type B is milder and can present at any time in life Diagnosis includes an examination blood tests and genetic testing While treatment consists of supportive