Niemann-Pick disease is a group of rare, inherited disorders that cause fatty. substances to build up in the body and brain. Thus, the chronic accumulation of these materials can cause severe damage to organs such as the brain, liver, spleen and lungs. This disorder, named after the German doctors Albert Niemann and Ludwig Pick who first identified the disease in the early 20th century, has remained a source of frustration for patients, families and the medical community.
Types of Niemann-Pick Disease
There are several varieties of Niemann-Pick Disease which vary in their causes and rate of progression:
Type A:
Infantile Niemann-Pick Disease, known as Type A, is the most severe type. It usually appears in the first months of life. It results in severe neurological deterioration and the liver and spleen get larger (hepatosplenomegaly). The majority of children with Type A will not live beyond early childhood.
Type B:
Also known as juvenile or chronic visceral Niemann-Pick Disease, Type B generally arises later in childhood or in adolescence. It is associated with similar fat deposition, but without major neurologic symptoms. Many people with Type B can live into adulthood, but they often have respiratory problems and enlarged organs.
Type C:
In contrast to types A and B, Niemann-Pick Disease Type C (NPC) is associated with distinct genetic and biochemical pathways. NPC interferes with the body’s ability to move cholesterol and other fats (lipids) inside cells, resulting in a knee-deep accumulation of these substances in a range of tissues. Symptoms typically manifest in childhood—although they can appear at any age—and are mostly neurological, such as unsteadiness of gait, declining intellectual functioning, seizures, and behaviors such as depression and psychosis.
Causes
Niemann-Pick Disease Types A and B are due to mutations in the SMPD1 gene resulting in a deficiency of an enzyme called acid sphingomyelinase (ASM). In the absence of sufficient ASM, a fatty substance called sphingomyelin accumulates in cells.
Type C results from mutations in the NPC1 or NPC2 gene that are required for transporting lipids within cells. This perturbation causes cholesterol and lipids to build up in an irregular fashion.
The disorder is inherited in an autosomal recessive manner, which means an affected child must inherit a faulty gene from both parents.
Symptoms
Symptoms of the disease will vary according to the type and degree of disease, but usually include:
- Growth of the liver and spleen (hepatosplenomegaly)
- Eating problems (in babies)
- Failure to thrive
- Developmental delays
- Problems coordinating movements (ataxia)
- Slurred speech
- Difficulty swallowing
- Cognitive decline
- Seizures
- Psychiatric problems (Type C in particular)
- Infections, especially upper respiratory infections (more common in Type B)
Diagnosis
Diagnosis of Niemann Pick Disease is usually based on the following:
- Blood tests and bone marrow aspiration for lipid deposition
- Enzyme assays for detection of the activity of acid sphingomyelinase (for A and B types)
- Genetic testing to look for mutations in the SMPD1, NPC1, or NPC2 genes
- Skin biopsy (fibroblast culture) to look for cholesterol movement in the cells (for Type C)
- Imaging tests such as MRI to find brain abnormalities
It is important that it is detected at an early stage to treat symptoms and enhance quality of life.
Treatment
Children with Niemann-Pick Disease, currently, there is no cure, but supportive care and specific treatments can help relieve symptoms:
- Enzyme replacement therapy (ERT): Currently under investigation, and therapy of Type B may be achieved by replacing the faulty enzyme.
- Miglustat (Zavesca): An oral drug, it is cleared for treating neurological problems in certain countries for Type C. It slows the production of some lipids.
- Supportive therapies: Physical, occupational and speech therapy and nutritional support can do a lot for quality of life.
- Bone marrow transplant: Attempted in some cases of type B, with varied success.
- Symptomatic treatment: Seizure suppression, psychiatric care, and treatment of respiratory distress are key components of care.
Living with Niemann-Pick Disease
Learning your child has Niemann-Pick Disease is not easy. It takes a diverse team of healthcare professionals – genetic counselors, neurologists, hepatologists, pulmonologists, therapists – to treat the disease. Emotional support in the form of counseling and support groups for patients and families can also be very helpful.
Advances in research, treatment and advocacy provide hope for better treatments — and, one day, a cure.