Niemann-Pick Disease Type B
Description
Niemann-Pick disease type B (NP-B) is a rare, inherited metabolic disorder that primarily affects the nervous system and other organs. It is caused by a deficiency in the enzyme sphingomyelinase, leading to the accumulation of sphingomyelin in various cells, particularly in the brain, liver, spleen, and bone marrow. This accumulation disrupts normal cellular function, leading to a range of symptoms that can vary in severity and age of onset.
Genes Involved
Niemann-Pick disease type B is caused by mutations in the SMPD1 gene, located on chromosome 11. This gene provides instructions for making the enzyme sphingomyelinase, which is responsible for breaking down sphingomyelin. Mutations in this gene lead to a deficiency of sphingomyelinase, causing the buildup of sphingomyelin.
Recognizing the Signs and Symptoms
The signs and symptoms of NP-B typically appear in infancy or early childhood and can include:
- Delayed development: Slowed growth, delayed speech, and motor milestones.
- Enlarged liver and spleen: Hepatosplenomegaly.
- Neurological problems: Seizures, muscle weakness, loss of coordination, and intellectual disability.
- Cherry-red spot: A red spot in the eyes, visible during an eye exam.
- Vision problems: Difficulty seeing, particularly in low light.
- Breathing difficulties: Respiratory distress.
- Feeding difficulties: Poor appetite, vomiting, and difficulty swallowing.
- Bone marrow failure: Decreased production of blood cells.
- Progressive neurodegeneration: Worsening neurological symptoms over time.
Causes
Niemann-Pick disease type B is an autosomal recessive disorder. This means that an individual must inherit two copies of the mutated SMPD1 gene, one from each parent, to develop the condition. If an individual inherits one copy of the mutated gene, they are considered a carrier and will not develop the disease but may pass the mutation onto their children.
Inheritance/recurrence risk
The risk of having a child with NP-B depends on the genetic status of the parents. If both parents are carriers, there is a 25% chance for each pregnancy that their child will inherit two copies of the mutated gene and develop NP-B. There is a 50% chance their child will be a carrier like themselves and a 25% chance their child will not inherit any mutated genes. Genetic counseling and carrier testing can help couples understand their risk and make informed decisions about family planning.
