Sphingomyelinase Deficiency Clinical Presentation

Updated: Aug 18, 2016
  • Author: Lynne Ierardi-Curto, MD, PhD; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Niemann-Pick disease (NPD) type A

The clinical presentation and course of NPD type A is relatively uniform and is characterized by normal appearance at birth. The first symptom detected is usually the presence of hepatosplenomegaly, which is evident at age 3 months and becomes progressively massive. Affected infants exhibit feeding problems, failure to thrive, recurrent respiratory tract infections, and irritability. Mild hypotonia may be evident by age 6 months, followed by progressive loss of tone and deep tendon reflexes. The disease course is characterized by developmental delay followed by regression. Psychomotor development does not progress beyond the 12-month level. With disease progression, loss of motor function and deterioration of intellectual capabilities occur. In the final stages, spasticity and rigidity are evident, and the affected child is completely unable to interact with the environment.

Atypical presentations of NPD type A have been reported, including unilateral tremors and ipsilateral hemiparesis with regression of milestones followed by the development of hepatosplenomegaly. [9]

NPD type B

The clinical presentation and course in patients with NPD type B disease is milder and more variable. The condition is diagnosed in most patients in infancy or childhood when enlargement of the liver, spleen, or both is detected during routine physical examination.

At diagnosis, patients with NPD type B also have evidence of mild pulmonary involvement, usually detected as a diffuse reticular or finely nodular infiltration on chest radiograph films.

In many patients, hepatosplenomegaly is particularly prominent in childhood; however, with increasing linear growth, the abdominal protuberance decreases and becomes less conspicuous.

In mildly affected patients, splenomegaly may not be noted until adulthood, and disease manifestations may be minimal.

In most patients with NPD type B, decreased pulmonary diffusion caused by storage of sphingomyelin in pulmonary macrophages becomes evident in childhood and progresses with age. Severely affected individuals may experience significant pulmonary compromise by age 15-20 years. Such patients have low PO2 values and dyspnea on exertion.

Recurrent pneumonia and life-threatening bronchopneumonias may occur, and cor pulmonale has been described. Severely affected patients may also have liver involvement leading to life-threatening cirrhosis, portal hypertension, and ascites.

Clinically significant pancytopenia caused by secondary hypersplenism may require partial or complete splenectomy, although removal of the spleen should be avoided because it results in rapid progression of the pulmonary disease.

Some patients with NPD type B may have associated neurologic findings, including cerebellar signs, nystagmus, extrapyramidal involvement, and intellectual disability.

Patients with NPD type B disease who undergo splenectomy frequently have worsening of pulmonary symptoms. Hepatosplenomegaly is prominent in childhood, but with increasing linear growth, abdominal protuberance decreases and becomes less conspicuous. In mildly affected patients, splenomegaly may not be noted until adulthood and disease manifestations may be minimal.


Physical Examination

Patients with Niemann-Pick disease (NPD) type A disease usually have a cherry-red macula on ophthalmologic examination. The cherry-red macula is the only normal part of the retina, and it is accentuated by the deposition of gangliosides in the surrounding retinal ganglion cells. However, the classic cherry-red spot is usually not observed early in the disease. In NPD type B disease, as many as one third of patients also have a cherry-red spot or macular haloes.

Hepatosplenomegaly is a common feature. In NPD type A disease, it typically becomes massive. In NPD type B disease, hepatosplenomegaly can widely vary. Some patients with NPD type B have massive enlargement, whereas others have milder enlargement that may remain unnoticed for years.

Patients with NPD type A have progressive neurodegeneration, and attainment of milestones does not progress beyond 10 months in any domain. Motor milestone attainment rarely progresses beyond the ability to sit with assistance. Progressive hypotonia and loss of deep tendon reflexes results in loss of previously achieved milestones. The neurologic degeneration is relentless, leading to a spastic state. Seizures are not common. Most patients with type B disease have normal findings on neurologic examination, although some patients have been described with peripheral neuropathy, extrapyramidal signs, psychiatric symptoms, and learning disabilities. In addition, some patients reportedly have normal early development but loss of language skills and onset of ataxia beginning around the third year of life.

Patients with moderate-to-severe NPD type B disease typically experience growth retardation in childhood and attain a final adult height that is less than expected based on familial heights.

Examination of the skin in patients with NPD type B disease may reveal extensive bruising. Patients with severe hypersplenism may also have petechiae.

Findings on auscultation of the lungs are usually normal in the absence of an intercurrent respiratory tract infection.

Cardiac examination findings are usually normal in the absence of valvular dysfunction.