SMPD1-related Niemann-Pick disease (NPD) is a condition where the body struggles to break down a fatty substance called sphingomyelin due to a lacking enzyme called acid sphingomyelinase. This leads to a buildup of sphingomyelin in the body, causing cell death and making it difficult for certain organs to function properly.
Mutations in the SMPD1 gene can result in either the type A or type B form of NPD. NPD type A (NPD-A) brings about intellectual disability, loss of motor skills, and an increase in the size of the liver and spleen, among other symptoms. Sadly, the disease is often fatal by the age of two or three. Signs of NPD-A usually appear within the first few months of life. By six months, infants with the disease struggle with feeding, have a swollen abdomen, and begin to lose the motor skills they developed. Seizures and spastic movement are common. Most won’t learn to sit, crawl, or walk independently. They have weak muscle tone and develop cherry-red spots in their eyes. Many may show a yellow tint to the skin and eyes (jaundice). Intellectual and motor skills decline rapidly. These children may experience vomiting, irritability, lung infections, and difficulty sleeping.
Unlike type A, which is fatal in early childhood, individuals with NPD-B have a less severe course and may live into adulthood. Common symptoms include an enlarged liver and spleen, a gradual decline in lung function with repeated respiratory infections, and slow physical growth, leading to shorter stature. They usually have abnormal lipid levels in their blood, which can result in heart disease later in life. Those with NPD-B may also have a reduced number of blood platelets, needed for blood clotting. These symptoms may not be present at birth but might develop in late childhood or adolescence. Individuals with NPD-B usually don’t have the nervous system complications found in NPD-A, but some may experience a mix of both NPD-A and NPD-B features.
This condition is caused by pathogenic (disease-causing) variants in the SPMD1 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 90 chance to be a carrier.
Other names for this condition are lipid histiocytosis, neuronal cholesterol lipidosis, sphingomyelin lipidosis, and sphingomyelinase deficiency.