Niemann Pick Disease - Overview, Symptoms, Diagnosis and Treatment



Neimann picks disease, is an uncommon metabolic disorder that affects the ability of the body to break down different types of fats like cholesterol or lipids within the cells. This results in an accumulation of excessive harmful levels of fatty substances in the cells, more specifically in the lysosomes(a part of the cell that contains digestive enzymes); hence it can also be classified as a lysosomal storage disorder.

CAUSES AND TYPES

Neimann picks disease can present with a wide range of symptoms at any age however it is most commonly seen in children and affects multiple organs like the brain, liver, spleen, bone marrow, or nerves. It is an autosomal recessive inherited disorder, where both the mother and father of the affected child are carriers of an abnormal gene.

There are multiple subtypes of Neimann picks disease that determines the affected patients' severity and symptoms. The 4 major types are

Type A(neurological type): when there is a deficiency of enzyme sphingomyelinase due to SMPD 1 gene mutation resulting in accumulation of sphingomyelin in the lysosomes. It is more common in infants, results in enlargement of the liver and spleen called Hepatosplenomegaly, and also affects the nervous system. This results in severe growth retardation, and progressive brain disease, and unfortunately the children affected generally have a short life span.

Type B(visceral type): this subtype has features very similar to Type A but is more commonly present in school-aged children, has less severe symptoms, and generally doesn't affect the brain or nerves.

Type C1 & C2: this subtype of Neimann picks disease there is a mutation of the NPC1 or NPC2 gene resulting in difficulty transporting fatty substances or cholesterol within the cells resulting in accumulation. The severity of the life expectancy of an affected child depends on the age of symptom presentation.

SYMPTOMS

The symptoms, severity of involvement, the age of presentation, and the life span of affected patients are greatly influenced by the different types of Neimann picks disease. The most commonly associated symptoms are

  • Hepatosplenomegaly(enlarged liver and spleen)
  • Jaundice
  • Early-onset symptoms like loss of muscle tone, delayed motor milestones, loss of vertical eye movements
  • Onset at childhood may present with clumsiness, learning disability, difficulty walking or swallowing, speech disturbance, or seizures
  • Adult-onset symptoms are also more commonly due to brain involvement and may present with movement disorders like tremors, difficulty walking or cognitive impairment.

    • DIAGNOSIS

    Due to the rare nature of the disease, the diagnosis of this disease can be challenging and is based more on cumulative history taking, physical examination, and the specific cluster of symptoms in a specific age group. The other available diagnostic tools are

  • Testing of patients skin cells for accumulation of fatty substances through staining techniques
  • Newborn screening with liver biopsy
  • Blood Biochemical markers for lipids or cholesterol
  • Molecular Genetic testing especially for type C Neimann picks disease(NPC1 & NPC2)
  • Prenatal testing for type C can also be done in people with a family history of Neiman Picks and Is generally performed on cells extracted from the mother at around 11 weeks of pregnancy(chorionic villous sampling)
  • Genetic testing to identify carriers and determine couples who are at high risk of having a child with Neimann picks disease
  • Imaging with MRI brain can be done in late-onset adult-type disease

    • TREATMENT

    There is no specific or curative treatment available for Neimann picks disease however to improve the overall condition of the affected patient the treatment is focused more on a coordinated systematic approach by different specialties of doctors.

    The different symptoms can be controlled through regular testing of cholesterol levels, anti-lipid medications like statins, platelet transfusions especially in type B, semisolid diet in case of difficulty swallowing, anti-seizure medications, speech therapy, medications to control tremors, physiotherapy and psychiatric counseling as most patients suffer from difficulty with sleep resulting in anxiety or depression.

    Genetic counseling and comprehensive family support also play an important role in the proper integrated management of the affected patient.

    Bone marrow transplantation, stem cell transplantation, and enzyme therapies are also being tested to understand the overall improvement of the symptoms or reduce the progression.

    Recent studies have also shown that a drug called Zavesca Migulstat is useful in the improvement of neurological symptoms of Neimann picks type C.

    Several clinical trials of multiple investigational therapies are also being studied giving us hope for a better and more effective treatment for Neimann Picks disease in the near future.