Acid Sphingomyelinase Deficiency (ASMD): Causes, Symptoms,Treatment

 

Acid Sphingomyelinase Deficiency or ASMD or generally called as Niemann-Pick disease also known as acid sphingomyelinase-deficient Niemann-Pick disease which

Can be generally described as a rare genetic disorder which typically develops a deficiency of the enzyme acid sphingomyelinase in the body. The most important role of acid sphingomyelinase in your body is helps you to digest the lipid called sphingomyelin which is usually named as fatty substance that will be found in the animal cell membrane.

Types

• Niemann-Pick disease type A (NPD-A)

• Niemann-Pick disease type B (NPD-B)

• Niemann-Pick disease type A/B (NPD-A/B)

Causes

The most common cause of Acid Sphingomyelinase Deficiency is any mutation that happens in the gene called sphingomyelin phosphodiesterase-1 (SMPD1) gene. The gene named SMPD1 generally 

The gene named SMPD1 typically develops instructions for generating a protein in the body which plays a major role in overall functioning of the body. If any mutation happens in a gene, it causes imbalance or inefficiency in the production of the protein.

The SMPD1 gene releases Acid Sphingomyelinase, this type of gene mutation usually creates a deficiency in production and overall functioning of the ASM enzyme. These ASM enzymes in the body help you to break down lipids present in the chromosome’s short arm which can be typically contained in the nucleus of human cells.

Unusual collection of sphingomyelin acid levels in many types of tissues of the body by the reduced level of ASM enzyme level in the body.

Signs & symptoms of Acid Sphingomyelinase Deficiency

Symptoms of ASMD will vary in both adults and children, which can range from real life threatening complications to mild illness.

Severe symptoms might be seen in the case of type A Niemann-Pick disease:

• Hepatosplenomegaly - unusual enlargement of the liver and/or spleen

• Ascites - in abdomen, collection fluids present

• Jaundice- appear yellow colour of the skin and whites of the eyes ( mostly seen in newborns)

• Cherry red spots in the eyes

• Collection of sphingomyelin in the lungs

• Feeding Problems

• Often Vomiting

• Significant Gastrointestinal Reflux

• Constipation

• Nausea

• Progressive Loss Of Muscle Tone (Hypotonia)

• Irritability

• Loss Of Reflexes

These symptoms create more complications for infants in future like often vomiting, Constipation, and Feeding difficulties which lead to FTT- failure to thrive or collection of sphingomyelin in the lungs.

In infants, these symptoms create more complications in future, which includes more often vomiting, Constipation, and Feeding difficulties which will gradually lead to failure to thrive ( FTT) or collection of sphingomyelin in the lungs can lead to Possible respiratory problems, breathing difficulties, and lung collapse.

Other than physical symptoms of an infant, the overall psychological (mentally) and neurological (nerves) progress of an infant also faces some obstacles. Children ages 9 to 12 months face some difficulties to achieve general milestones. They also lose their control of motor skills and can experience some deep neurologic deterioration which will be followed by stiffness of muscles and increased muscle tone.

Severe symptoms of Type B Niemann-pick Disease which includes:

• Hepatosplenomegaly

• Thrombocytopenia - Progressive enlargement of the spleen 

• Abdominal pain

• Some degree of liver disease like frank cirrhosis, liver failure

• Deterioration in lung function

• Dyspnea - Difficulty breathing upon exertion

• Early coronary artery disease

• Recurrent pneumonia

• Osteopenia which means weakening and thinning of the bones

• Limb and bone pain

Combine with physical symptoms, neurological and psychological unusual problems like:

• Nystagmus - involuntary eye movements

• Unknown cerebellar signs like abnormal manner of walking and clumsiness

• Peripheral neuropathy ( may include loss of sensation or addition of unusual sensations like burning, tingling, or pricking along the affected nerves)

Some Other common symptoms may include:

• Growth delays

• Low body mass index

• Skeletal maturation

• Dyslipidemia - unusual levels of lipids in the blood serum

• low levels of high-density lipoprotein called as HDL-cholesterol or good cholesterol

• High serum concentrations of low-density lipoprotein-cholesterol (LDL-C)

• Hypertriglyceridemia - High triglyceride levels

Hence type B ASMD develops symptoms from infants to adults, But you have less chances of diagnosing the symptoms in the early stages of life. Symptoms of Type B of ASMD include symptoms of Type A but it has less effective manner.

Other types of ASMD are Type A and Type B which show some related illness which usually replicates the type C or it cannot replicate any symptoms in any cases at all.Some of the symptoms which includes:

• Types of metabolic disorders which includes mucopolysaccharidoses and other lysosomal storage disorders

• Galactosemia

• Sialidosis

• Gaucher disease

• Galactosialidosis

• Wolman disease

• Cholesteryl ester storage deficiency

Diagnosis

Your healthcare professionals will prescribe the accurate series of testing which depends upon your medical history and combination of symptoms. These tests will be used to identify the root cause of the symptoms.  Some key factors are commonly diagnosed in this case are:

• ASM enzyme activity

• Peripheral blood leukocytes (WBC)

• Cultured skin fibroblasts which means connective tissue cells of the skin

If the above diagnosis test results less than 10% of confirmation, then in this case, your doctor will move to another method of diagnosis ASMD by molecular genetic testing. This test helps to confirm the presence of ASMD and it also helps to detect the mutants in the SMPD1 gene. But this test is very hard to perform because this test needs specialised laboratories and settings which are hard to locate.

Treatment

After the diagnosis step, your healthcare professional will coordinate with a specialist to treat every associated symptom. This specialist team includes neurologists, pediatricians, hepatologists, ophthalmologists, genetic counselors and other types of physicians that will develop a systematic and comprehensive treatment plan for the patients. In this team, a psychiatrist or a general counselor is also included which helps to ensure overall health by providing psychosocial support for both patients and their family.

Type A Niemann-Pick Treatment may include:

• Physical and occupational therapy

• Periodic nutritional assessment

• Gastronomy - Implantation of a feeding tube ( to make sure proper nutritional intake)

• Nocturnal sedatives - To cure sleep-associated disorders

Type B Niemann-Pick Treatment may include:

• Dyslipidemia and hyperlipidemia treatment

• Osteopenia treatment

• Nutritional support

• Blood transfusions ( for thrombocytopenia )

• Supplemental oxygen ( serious lung disease )

• Liver transplantation ( liver failure )

Frequently Asked Questions

Q1. What are the effects of sphingomyelinase deficiency?

Ans: With disease progression, loss of motor function occurs, and in the final stages, spasticity and rigidity are evident. Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability.

Q2. What deficiency causes Niemann-Pick disease?

Ans: Niemann-Pick disease (NPD) is a lysosomal storage disease caused by acid sphingomyelinase deficiency (ASMD), which catalyzes the hydrolysis of sphingomyelin (SM) to ceramide and phosphocholine.

Q3. What is the function of acid sphingomyelinase?

Ans: Acid sphingomyelinase (ASM) is a key enzyme in sphingolipid metabolism that converts sphingomyelin to ceramide, thereby modulating membrane structures and signal transduction.

Q4. What is another name for Niemann-Pick disease?

Ans: Niemann-Pick disease (NPD), also called sphingomyelin-cholesterol lipidosis, is a group of autosomal recessive disorders.

Q5. What foods contain sphingomyelin?

Ans: It is mainly derived from fish, meat, milk and egg products.