Niemann-Pick disease

Niemann-Pick disease basal

Last Updated February 21st, 2019

Overview of Niemann-Pick disease

In the recent years, the statistics of Global Genes have shown that there are nearly 7000 rare diseases in the world and an estimated 300 million people live with those diseases. They have also established the fact that 6% of the babies are born with rare genetic diseases and about 30% of them die before the age of five.

A large number of these diseases are caused by autosomal recessive or dominant genetic traits. Niemann-Pick is one such disease where neurological and hepatic syndromes are observed. Children usually die from the disease at a very young age, in the toddlerhood in most cases. A few people with the disease tend to have a normal lifespan.

 

What is Niemann-Pick disease?

Niemann-Pick disease is a collective name for a group of inherited metabolic disorders which results in hepatic and neurological syndromes. Diagnoses of these patients have shown an accumulation of sphingomyelin in the lysosomes of the cells. Abnormal metabolism of the sphingolipids occurs in this disease. Sphingolipids are nothing but the fats present in the cell membranes. So this condition is often termed as sphingolipidosis, which is one of the major diseases belonging to the category of Lysosomal storage diseases.

 

What causes Niemann-Pick disease?

Niemann-Pick disease is inherited in an autosomal recessive pattern. This implies that both copies of the inherited genes should be defective for the disease to manifest fully. The disease primarily arises due to mutations in the SMPD-1 gene. If both the parents are the carriers of Niemann-Pick, there is a 25% chance of the disease getting passed on to the next generation.

 

What are the main signs and symptoms?

Niemann-Pick spleenNiemann-Pick disease mainly presents with hepatic, neurological and skeletal symptoms. The symptoms basically are manifested in those organs where the sphingomyelin accumulates.

Hepatic symptoms  

The patients may exhibit the following hepatic symptoms-

When these clinical features persist for a long period of time, the following symptoms may also arise-

  • Yellowish discoloration of the skin
  • Sclera, conjunctiva and mucosa turns pale yellow (in advanced stages)
  • Dark yellow or brownish discolouration of urine
  • Dark stool
  • Irritation of skin
  • Severe loss of appetite
  • Abnormal weight loss in advanced stages
  • Extreme fatigue
  • Occasional pain in the upper right portion of stomach
  • Nausea and vomiting
  • Occasional headaches
  • Fever (occasional)

Neurological symptoms

Niemann-Pick disease basalThe neurological symptoms mainly arise from the build-up of sphingomyelin in the central nervous system and the cerebellum. The following neurological symptoms are observed-

Ataxia: This results in an abnormal gait. Following are the main features-

  • Unstable gait
  • Abnormal posture (while standing)
  • Fumbling steps
  • Prominent trembling (intention tremor)
  • Problems in writing
  • Slurred speech (dysarthria)
  • Cannot perform very fast and alternating movements
  • Problems judging distances or range of movements
  • Loss of check reflex (rebound phenomenon)
  • Heavy strikes during walking
  • Lack of equilibrium

Dysarthria: This presents as unclear and poorly formed speech. The symptoms are-

  • Slurred speech
  • Prolongation of certain syllables while talking
  • Breathy or husky voice
  • Random breakdown of articulation
  • A monotonous pitch with no modulation
  • Absence of pauses within speech
  • An abnormal nasal tone (hypernasality)

Dysphagia: It is a condition marked by a difficulty in swallowing. The main signs are-

  • Problems in controlling the food content in the mouth
  • Lack of capacity to control the salivary content inside the mouth
  • Not being able to begin swallowing at one go
  • Tendency of coughing and choking while swallowing food
  • Feeling of cervical obstruction while swallowing
  • Pain during swallowing food
  • Unexplained wetness of voice after swallowing food
  • Nasal regurgitation

Dystonia: It is a muscular disorder characterised by the following symptoms-

  • Painful and involuntary twisting of the neck
  • Head pulled near to the chest
  • Involuntary eye-spasms (Blepharospasms)
  • Problems in tongue and jaw movements
  • Difficulties in voice modulation
  • Problems in moving the hands and the arms
  • Sudden loss of muscle tone while laughing or talking (Gelastic cataplexy)

Some of the other neurological symptoms are- loss of voluntary eye movements, also called supranuclear gaze palsy. This results from the dysfunctions of the upper brainstem. Some patients may experience dementia and seizures when the cerebral cortex and the subcortical structures suffer damage.

Skeletal symptoms

A number of Niemann-Pick patients suffer from multiple skeletal symptoms which are given below-

  • Enlargement of the bone marrow cavities
  • Thinning of the cortical bone
  • Distortions of the hip bone (coxa vara)

 

What are the different types of Niemann-Pick disease?

According to the inheritance pattern and the manifestation of the symptoms, Niemann-Pick disease is of four types-

  • Type A: It results from the mutations in the SMPD1 gene. This results in a reduced activity of the lysosomal enzyme acid sphingomyelinase, which is responsible for the breakdown of the lipid sphingomyelin. This leads to classic infantile symptoms. Histological evidence show lipid-laden macrophages in the bone marrow and sea-blue histiocytes.
  • Type B: The etiology is the same as that of Type A, but visceral symptoms are observed in this case.
  • Type C: This affects the protein responsible for transporting the lipids. It is a type of juvenile Niemann-Pick disease and has two subtypes- Type C1 and Type C2. C1 is the common form, while C2 is a relatively rare variant.
  • Type D: The patients in this category are found to share a common mutation in the NPC1 gene.

 

Diagnosis,  treatment, & prevention

Niemann_pick neuronNiemann-Pick disease can be detected through genetic tests. In the current scenario, there is no cure for the Niemann-Pick disease. The treatment is mainly supportive and aims to provide symptomatic relief.

  • Type A: Most of the children die in infancy. Some of them live up to the age of 4 years. There is no treatment for NPA. Only supportive care can be rendered.
  • Type B: Research is going on to establish definitive treatment options for NPB. Several treatment modalities that have been tried are enzyme replacement therapy, bone marrow transplants, gene therapy etc. Restriction on the diet does not help in preventing the accumulation of lipids in cells and tissues.
  • Type C: In order to cope up with mobility issues, physical therapy can be chosen. In order to prevent the build-up of fatty substances (such as cholesterol) in the body, an enzyme inhibitor called miglustat is currently being used. Miglustat prevents the body from producing fatty substances.

Families, who have carriers of the Niemann-Pick Disease, are advised to undergo genetic counseling and genetic testing in order to prevent this condition in the future generations. Genetic counseling for couples having a family history is worthwhile.

Facts

  • The Niemann-Pick disease is named after German physicians Albert Niemann and Ludwig Pick.
  • There are approximately 1,200 cases of the Niemann-Pick disease worldwide. Most of them are type B.
  • Type C Niemann-Pick Disease (NPC) has an estimated number of 500 cases diagnosed worldwide.

Facts

  • Niemann-Pick Disease is always fatal. In Type C, the sufferers usually die before the age of 20 years. Moreover, some of them die before 10 years.
  • Acid sphingomyelinase enzyme deficiency results in Niemann-Pick Disease, type A and B.
  • Individuals suffering from the type A Niemann-Pick Disease (NPA) usually die between the ages of 2 to 4 years.

Facts

  • The incidence of both NPA and NPB is estimated to be 1 in every 250,000 individuals.
  • The incidence of NPC is estimated to be 1 in every 150,000 individuals.
  • Each pregnancy has a 25% possibility of producing an affected child in case both the parents are carriers of the disease (each one has only one copy of the altered gene).

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Dos and Don'ts

Dos
  • Visit your doctor if you see symptoms such as dementia, seizures, psychiatric disorders, mental retardation, lung problems peripheral nerve problems, poor coordination etc.
  • Maintain hygiene so as to prevent infections as the child is susceptible to infections on the account of a compromised immune system.
  • Consult a registered general physician and contact support groups. This might help you to learn ways to manage the complications of the disease in a better manner.
Don'ts
  • Get annoyed, irritated or impatient, with children having mental retardation or learning disorders.
  • Miss the follow-up sessions of doctors, physical therapists, psychiatrists etc.

 

 

 

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Glucose-6-Phosphate Dehydrogenase (G6PD) test Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that is found in every cell of the body and it plays…
Strep throat pain
Anti-Streptolysin-O Test The ASO or Anti-Streptolysin-O is a blood test designed to check for the presence of streptococcus bacterial infection…
myelogram
Myelography Myelography is an important diagnostic tool that is used to investigate and identify abnormalities in the spine and…
Jicama: A fiber-rich tuber for your weight loss goals Pronouced as HEE-kah-ma, Jicama is the "new kid on the block" that has taken the world by the…
cold flu sinus treatment
How to beat the common cold, flu, and sinus infection instantly? Can you guess some of the easiest tricks to treat cold and sinus infections? How are these different…
paleo keto diet
Paleo vs. Keto: Which diet plan is best suited for your body goals? Is eating like a caveman the right way to go? Can you really eat fats to burn fats…
Spirulina: Battle diabetes and cholesterol with this blue-green algae Spirulina, a species of salt water algae, has now become a billion dollar industry. How you can use…