Dermatologic Manifestations of Niemann-Pick Disease Clinical Presentation

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Apr 25, 2011
 

History

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. Note the following:

  • 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.[4] 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, 5] 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.[6]
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Physical

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.

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Causes

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.

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Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Santiago A Centurion, MD  Staff Physician, Department of Dermatology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey

Santiago A Centurion, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, and Sigma Xi

Disclosure: Nothing to disclose.

Danielle Lann, MD  Staff Physician, Dermatology, UMDNJ-New Jersey Medical School

Disclosure: Nothing to disclose.

Naomi Bartnoff, MS  Former Genetics Counselor, Center for Human and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School

Disclosure: Nothing to disclose.

Specialty Editor Board

Albert C Yan, MD  Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania

Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, Society for Investigative Dermatology, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Van Perry, MD  Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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