ASMD stands for acid sphingomyelinase deficiency, a rare genetic disorder previously known as Niemann-Pick disease types A and B. The name comes from the enzyme that’s missing or underactive in people with the condition. It affects roughly 1 in every 250,000 births worldwide.
What ASMD Actually Is
ASMD is a lysosomal storage disease, meaning it involves a buildup of material inside cells that the body can’t properly break down. Normally, an enzyme called acid sphingomyelinase breaks apart a fatty substance called sphingomyelin into smaller components your cells can recycle. In ASMD, mutations in the SMPD1 gene cause this enzyme to be absent or severely reduced. Without it, sphingomyelin and other fats pile up inside cells, particularly in the liver, spleen, lungs, and sometimes the brain.
The condition is inherited in an autosomal recessive pattern, which means a child needs to receive a faulty copy of the gene from both parents to develop the disease.
Why the Name Changed From Niemann-Pick
For decades, this condition was grouped under the umbrella of Niemann-Pick disease, which also included a separate condition called type C. That grouping created confusion because Niemann-Pick type C involves an entirely different gene and mechanism. The shift to “ASMD” gives the condition a name tied to its actual cause (the missing enzyme) rather than a historical label that lumped together unrelated diseases.
Types of ASMD
ASMD exists on a spectrum, but clinicians generally recognize three forms based on severity and age of onset.
Type A (infantile neurovisceral): The most severe form. Infants typically develop an enlarged liver and spleen by 2 to 4 months of age. The brain is heavily affected, and neurological decline progresses rapidly. Type A is fatal in early childhood.
Type B (chronic visceral): This form spares the brain but still causes significant organ damage over time. Enlarged liver and spleen, interstitial lung disease, shortness of breath, and frequent respiratory infections are common. People with type B can survive into adulthood, though the disease is progressive and complications can be serious.
Type A/B (chronic neurovisceral): An intermediate form with some neurological involvement alongside the organ symptoms seen in type B. Severity varies widely from person to person.
How ASMD Affects the Body
The fat buildup in ASMD concentrates in cells of the immune system called macrophages, which are found throughout the body. As these cells swell with undigested sphingomyelin, they damage the organs they inhabit. The liver and spleen bear the heaviest burden, often growing several times their normal size. This enlargement can cause abdominal pain, early fullness when eating, and abnormal blood counts because an oversized spleen traps and destroys blood cells faster than normal.
Lung involvement is the other major concern. Sphingomyelin accumulates in the lung tissue, causing a form of interstitial lung disease that reduces the lungs’ ability to transfer oxygen. Over time, this leads to worsening shortness of breath and a higher susceptibility to respiratory infections. Cholesterol and other lipids also build up, which can affect blood lipid levels and contribute to liver scarring.
How It’s Diagnosed
The gold standard for diagnosing ASMD is measuring the activity of acid sphingomyelinase in white blood cells. A result below 0.32 nmol/hour/mg protein is consistent with the diagnosis. An initial screening can be done with a dried blood spot test, but because that method can produce false results, a positive screen needs confirmation through the more precise white blood cell assay.
Genetic testing of the SMPD1 gene typically follows an abnormal enzyme result. This step matters because many genetic variants in SMPD1 are harmless or of unknown significance, so low enzyme activity is the critical piece of evidence. Genetic results alone, without confirmed enzyme deficiency, aren’t enough for a definitive diagnosis.
Treatment With Enzyme Replacement
In 2023, the FDA approved Xenpozyme (olipudase alfa), the first enzyme replacement therapy for ASMD. It works by providing the body with a functional version of the missing enzyme through intravenous infusions. The treatment is approved for both adults and children and targets the non-neurological symptoms of the disease, meaning it can help reduce liver and spleen size and improve lung function, but it does not cross into the brain.
This distinction is important: Xenpozyme can meaningfully improve quality of life for people with type B and some with type A/B, but it is not a treatment for the brain-related decline seen in type A. Before this therapy became available, management of ASMD was entirely supportive, focused on managing symptoms and complications rather than addressing the underlying enzyme deficiency.
How Rare ASMD Is
Studies across Europe, Australia, and the Middle East estimate that ASMD types A and B occur in roughly 0.3 to 0.6 cases per 100,000 live births. An Australian study placed the rate at about 1 in 248,000. Because the condition is so uncommon, many physicians have never seen a case, which contributes to diagnostic delays. People with type B in particular may go years with unexplained liver or spleen enlargement before the correct diagnosis is made.