Dermatologic Manifestations of Niemann-Pick Disease Clinical Presentation

Updated: Jul 19, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
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Patients with Niemann-Pick disease (NPD) type A have a progressive neurodegenerative course in infancy, and patients with Niemann-Pick disease type B have nervous system involvement that is linked to the appearance of a cherry-red macula. The amounts and the types of lipid storage in the reticuloendothelial system and the visceral organs in patients with type A and those with type B are also similar.

Niemann-Pick disease type A begins in the individual's first few months of life. Symptoms include the following:

  • Feeding difficulties

  • Abdominal enlargement within 3-6 months

  • Progressive loss of early motor skills

  • Rapid decline leading to death by the time the patient is aged 2-3 years

Biochemically, Niemann-Pick disease type B is similar to Niemann-Pick disease type A, but the symptoms are more variable. Abdominal enlargement may be detected in early childhood. Respiratory infections recur. No neurologic involvement is present.

Niemann-Pick disease type C usually affects school-aged children, but the disease may occur at any time from early infancy to adulthood. Symptoms may include the following:

  • Unsteadiness of gait, clumsiness, problems in walking

  • Difficulty in posturing of the limbs

  • Slurred, irregular speech

  • Learning difficulties and progressive intellectual decline

  • Sudden loss of muscle tone, which may lead to falls

  • Seizures

  • Tremors accompanying movement

A subclinical course of adult visceral Niemann-Pick disease type C1 appears to be rare. [5] Niemann-Pick disease type C may rarely lack neurological symptoms. This adult visceral form of Niemann-Pick disease type C is usually dominated by neurovisceral symptoms, may represent an underdiagnosed disease form, and should be considered in patients with isolated hepatosplenomegaly with foam cells in adulthood.

Niemann-Pick disease type C may be first seen with cataplexy, which may lead to its diagnosis. [3, 6] Cataplexy is rare and evident as a brief episode of bilateral loss of muscle tone with intact consciousness, triggered by a variety of strong emotions and, in particular, with unexpected laughter. The patient may develop "drop attacks" upon laughing. This inherited lipid storage disorder has considerable phenotypic variability. [7]


Physical Examination

Neurologic features include the following:

  • Mental retardation

  • Difficulty with upward and downward eye movements

  • Vertical supranuclear gaze palsy (Vertical supranuclear gaze palsy is highly suggestive of Niemann-Pick disease type C.)

  • Spasticity

  • Seizures

  • Myoclonic jerks

  • Ataxia

GI features include the following:

  • Hepatosplenomegaly

  • Jaundice

  • Hepatic failure

  • Ascites

Head, ears, eyes, nose, and throat characteristics include the following:

  • Cherry-red macular spot

  • Corneal opacification

  • Brown discoloration of the anterior lens capsule

Blood characteristics include the following:

  • Bone marrow foam cells

  • Easy bruisability

  • Anemia

Respiratory features include interstitial pulmonary infiltration. Cardiac features include coronary artery disease. Skin characteristics include nodular xanthoma. Growth characteristics include retarded physical growth.



See Pathophysiology.

An interesting parallel also exists between the up-regulation of apolipoprotein D in mice with Niemann-Pick disease type C and its enhanced expression in oligodendroglia in Alzheimer disease. Neurofibrillary tangles are a common neuropathologic feature of the 2 disorders; this finding suggests a relationship between apolipoprotein D and neurofibrillary tangles. Thus, the expression of apolipoprotein D appears to be coordinately impaired in Niemann-Pick disease type C as part of a generalized defect in cellular cholesterol trafficking.



Complications can include the following:

  • Mental retardation
  • Delayed development of physical skills
  • Blindness
  • Deafness
  • Progressive deterioration (Niemann-Pick disease [NPD] is a fatal disorder.)