Because ASMD is a highly variable disorder, it is important to note that affected individuals will not have all of the symptoms described below and that every individual case is unique. Some children will develop severe, life-threatening complications early in life; others have mild disease that may go undiagnosed well into adulthood. Parents should talk to their child’s physician and medical team about the specific symptoms and overall prognosis.
NIEMANN-PICK DISEASE TYPE A The severe, infantile form of ASMD, known as Niemann-Pick disease type A, can be distinguished from more mild forms, which have later onset. The initial symptom in most infantile cases is abnormal enlargement of the liver and/or spleen (hepatosplenomegaly), which can progressively worsen until the liver and spleen become massive. Significant accumulation of fluid in the abdomen (ascites) can also occur. Yellowing of the skin and whites of the eyes (jaundice) may occur during the newborn period. Additional symptoms during infancy include feeding problems, Constipation, Nausea, Vomiting, significant gastrointestinal reflux, Irritability, loss of reflexes, and progressive loss of muscle tone (hypotonia). Feeding difficulties and other abnormalities (e.g. frequent Vomiting) can result in failure to thrive. The accumulation of sphingomyelin in the lungs can result in recurrent respiratory infections and difficulty breathing, potentially resulting in life-threatening respiratory failure.
Most infants develop a condition known as cherry red spots in the eyes. A cherry red spot affects the macula, which is the region of the retina that contains light-sensing cells necessary for central vision. It is normally yellow. A cherry red spot is not always present in affected individuals.
The attainment of developmental milestones and overall development may be normal in the first several months. However, often by 9 to 12 months of age, development plateaus and affected infants lose previously acquired motor skills. Affected infants may experience profound neurologic deterioration and increased muscle tone and stiffness of muscles (spasticity), and the disorder is often fatal by 3 years of age.
NIEMANN-PICK DISEASE TYPE B Individuals with later onset forms of ASMD can develop symptoms from infancy to adulthood. Sometimes, these forms are collectively referred to as Niemann-Pick disease type B; they are, generally, milder than Niemann-Pick disease type A (infantile form). Individuals with mild forms can live until late adulthood and some may go undiagnosed until well into adulthood. Niemann-Pick disease type B is associated with systemic disease that can vary widely in severity and extent.
Hepatosplenomegaly is a common initial symptom and can range from mild to massive enlargement. Progressive enlargement of the spleen can cause low levels of platelets and white blood cells. White blood cells help to fight infection and a reduced number of these cells can leave an affected individual susceptible to infection. Platelets are specialized blood cells that allow the body to form clots to stop bleeding. A reduced number of platelets, known as thrombocytopenia, can lead to episodes of prolonged bleeding. Abdominal pain can result from enlargement of the liver and spleen. An enlarged spleen is at risk of rupturing, potentially resulting in life threatening bleeding into the abdominal cavity.
Some degree of liver disease is present in most individuals with type B disease. The majority have abnormal liver blood tests and some scarring in the liver. The scarring can range from mild without symptoms, to frank cirrhosis and liver failure.
Some affected individuals experience a gradual deterioration in lung function. For some individuals, lung involvement may be mild with no noticeable symptoms. Some individuals may develop difficulty breathing upon exertion (dyspnea). Other individuals may experience continued deterioration in breathing (respiratory) function with severe limitations in activity levels and oxygen dependence. Recurrent pneumonia may occur.
Individuals with late-infantile or later onset of ASMD usually do not develop neurological symptoms, but may develop mild symptoms, or, in rare cases, may develop clinically significant neurological symptoms. Some affected children and adolescents may develop rapid, involuntary eye movements (nystagmus) and cerebellar signs, which includes unsteady manner of walking and clumsiness. Intellectual disability and psychiatric disorders have also been reported. Abnormalities of the retina, the nerve-rich membrane lining the back of the eyes, and peripheral neuropathy may occur. Peripheral neuropathy is a general term for any disease affecting the nerves outside the central nervous system. Common symptoms include the loss of sensation or abnormal sensations such as tingling, burning, or pricking along the affected nerves.
Most affected children experience growth delays and low weight, although most eventually reach a near normal adult height. Delayed puberty and skeletal maturation may also occur.
Most individuals have osteopenia, or thinning of the bones. (Wasserstein et al, JIMD, 2013). Limb and bone pain have been reported.
A common finding in affected individuals is abnormal levels of lipids in the blood serum (dyslipidemia), specifically low levels of high density lipoprotein (HDL-cholesterol, aka “good cholesterol”), high serum concentrations of low density lipoprotein-cholesterol (LDL-C) and high triglyceride levels (hypertriglyceridemia). Affected individuals may be at risk early coronary artery disease.