Acid Sphingomyelinase Deficiency (ASMD) can present a wide range of signs and symptoms, which can vary significantly depending on the type and severity of the disease. Here are some common symptoms associated with ASMD:

General Symptoms

• Fatigue: Chronic tiredness that doesn't improve with rest².

• Growth Delay: Particularly in children, growth may be slower than expected³.

Organ-Specific Symptoms

• Enlarged Liver and Spleen³ (Hepatomegaly & Splenomegaly)

• Lungs:

  • Interstitial Lung Disease: Scarring of lung tissue leading to coughing and difficulty breathing⁴

  • Pulmonary Hypertension: High blood pressure affecting the heart and lungs⁴.

• Blood: Low platelet count, leading to easy bruising and bleeding³ (Thrombocytopenia)

• Gastrointestinal: Abdominal Pain and Diarrhea (Digestive issues)⁴.

Neurological Symptoms (more common in severe forms)

• Loss of Muscle Tone: Reduced muscle strength and control⁵.

• Brain Degeneration: Progressive loss of brain function⁵.

Other Symptoms

• Joint or Limb Pain: Discomfort in the joints or limbs².

• Frequent Infections: Due to compromised lung function⁴.

These symptoms can significantly impact daily life, leading to frequent hospital visits, increased medication use, and challenges in maintaining normal activities and relationships². If you or someone you know is experiencing these symptoms, it's important to consult a healthcare professional for proper diagnosis and management.

Generally, how someone presents clinically will be the main way to determine their subtype. There is no diagnostic test established to identify between the subtypes as of yet. Because this disease can appear like other disorders, people living with this condition are at risk of incorrect diagnoses.

Diagnosis is determined by a mix of clinical presentation, genetic tests and biochemical assessments and will involve several of the following⁶.

1. Clinical Evaluation: The process often begins with a visit to a general practitioner (GP) or pediatrician, who will take a detailed medical history and perform a physical examination. They will look for signs and symptoms consistent with ASMD, such as an enlarged liver or spleen, respiratory issues, or developmental delays.

2. Enzyme Assay: This test measures the activity of the acid sphingomyelinase enzyme in blood or skin cells. A significant reduction in enzyme activity is indicative of ASMD.

3. Genetic Testing: To identify mutations in the SMPD1 gene, which is responsible for producing acid sphingomyelinase. This test can also help differentiate between the different types of ASMD.

4. Imaging Studies: Imaging tests such as ultrasound, MRI, or CT scans may be used to assess the extent of organ involvement, particularly the liver and spleen.

5. Biopsy: In some cases, a biopsy of the liver or bone marrow may be performed to look for characteristic storage cells.

   
   

These methods help ensure an accurate diagnosis, although the process can be complex due to the variability of symptoms.

A specific DNA change can cause the SMPD1 (sphingomyelin phosphodiesterase 1) gene to become faulty⁷. This prevents cells from making enough Acid Sphingomyelinase protein, meaning sphingomyelin isn’t broken down and instead, builds up over time in the brain and/or body cells. This can lead to progressive cell and tissue damage which can be seen through various disease symptoms⁸. Depending on the DNA change, some people produce no Acid Sphingomyelinase (type A) while others produce a small amount (type B).

ASMD is inherited in an autosomal recessive manner. This means that for a child to be affected by ASMD, they must inherit two copies of the mutated gene, one from each parent. If both parents are carriers of the SMPD1 gene mutation, there is a 25% chance with each pregnancy that their child will have NPC, a 50% chance that the child will be a carrier like the parents, and a 25% chance that the child will not inherit the mutation at all.

Carrier parents typically do not show symptoms of the disease, which can make it challenging to identify the risk without genetic testing. Genetic counselling is often recommended for families with a history of ASMD to understand their risks and the implications for future pregnancies.

The Ashkenazi Jewish population carries 3 specific DNA changes in the SMPD1 gene which means they have a higher chance of having a child with a severe form of ASMD.

1 in 59 people in this population are estimated to carry one faulty SMPD1 gene copy⁹.

Treatment of ASMD conditions is complex and often requires a multi-disciplinary approach with a range of specialists to help manage symptoms.