Niemann-Pick disease, also known as sphingomyelin lipidosis, is caused by a congenital deficiency of sphingomyelinase, which prevents the normal breakdown of sphingomyelin. It is characterized by the systemic accumulation of sphingomyelin, particularly in the liver, spleen, and nervous system. This condition is inherited in an autosomal recessive manner. It is more prevalent among the Jewish population and has been frequently reported in China as well.

bubble_chart Clinical Manifestations

Based on the characteristics of disease progression, this condition can be divided into four types: a, b, c, and d. Among them, type a is the most common, accounting for approximately 85% of all cases, and is the typical form of the disease.

1. Type a (acute neurological type, or infantile type): 75% of cases manifest within 3 months, with rapid disease progression, delayed and regressive growth and development. Progressive decline in intellectual and motor development, early hypotonia followed by hypertonia, leading to spastic paralysis; further progression results in blindness, deafness, and unresponsiveness to sound or light stimuli; focal or generalized seizures may occur. Significant hepatosplenomegaly, emaciation, intermittent jaundice, and anemia; brownish-yellow pigmentation may appear on the skin. Fundus examination may reveal macular degeneration and cherry-red spots. Sphingomyelinase levels are markedly reduced. Most patients die from secondary infections by the age of 2–3.
2. Type b (chronic non-neurological type): Onset occurs in infancy, with slow disease progression. Hepatosplenomegaly is prominent, intelligence remains normal, and central nervous system involvement is rare. Niemann-Pick cell infiltration occurs in the lungs, and chest X-rays may reveal foxtail millet-like granular shadows. Sphingomyelinase levels are also significantly reduced. Death may result from pulmonary infections, but some patients survive into adulthood.
3. Type c (chronic neurological type): Onset typically occurs after the age of 2, with relatively slow progression. Neurological symptoms usually appear after the age of 5, manifesting as ataxia, speech impairment, intellectual disability, grand mal seizures, hypertonia, and hyperreflexia. Hepatosplenomegaly is mild. Sphingomyelinase activity is about 1/2 to 2/3 of normal levels. Most patients die between the ages of 5 and 15.
4. Type d (adult non-neurological type): Only observed in the population of eastern Canada. Onset occurs later, with slow progression. Neurological symptoms are usually absent. Hepatosplenomegaly is grade II. Fundus examination may reveal cherry-red spots. Enzyme deficiency is not significant. Patients may survive into adulthood.

bubble_chart Auxiliary Examination

1. Foamy Niemann-Pick cells can be found in bone marrow smears of all types. PAS staining often shows negative results in the center of vacuoles, with weakly positive cell walls. Acid phosphatase staining appears negative or weakly positive. In types B and C, Giemsa staining reveals numerous sea-blue granules in the cytoplasm of sea-blue cells. Under electron microscopy, lipid inclusions with multiple layers of membranes can be observed.
2. Enzyme activity assays in leukocytes or skin fibroblasts show reduced levels in types A, B, and C.
3. For those with a family history, prenatal diagnosis can be performed by measuring enzyme activity in amniotic fluid cells.

bubble_chart Treatment Measures

There is no specific treatment, mainly symptomatic treatment and prevention of infection. Splenectomy does not alter the prognosis.