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:
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Feeding difficulties
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Abdominal enlargement within 3-6 months
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Progressive loss of early motor skills
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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:
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Unsteadiness of gait, clumsiness, problems in walking
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Difficulty in posturing of the limbs
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Slurred, irregular speech
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Learning difficulties and progressive intellectual decline
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Sudden loss of muscle tone, which may lead to falls
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Seizures
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Tremors accompanying movement
A subclinical course of adult visceral Niemann-Pick disease type C1 appears to be rare. [6] 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. [4, 7] 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. [8]
Physical Examination
Neurologic features include the following:
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Mental retardation
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Difficulty with upward and downward eye movements
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Vertical supranuclear gaze palsy (Vertical supranuclear gaze palsy is highly suggestive of Niemann-Pick disease type C.)
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Spasticity
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Seizures
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Myoclonic jerks
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Ataxia
GI features include the following:
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Hepatosplenomegaly
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Jaundice
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Hepatic failure
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Ascites
Head, ears, eyes, nose, and throat characteristics include the following:
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Cherry-red macular spot
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Corneal opacification
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Brown discoloration of the anterior lens capsule
Blood characteristics include the following:
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Bone marrow foam cells
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Easy bruisability
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Anemia
Respiratory features include interstitial pulmonary infiltration. Cardiac features include coronary artery disease. Skin characteristics include nodular xanthoma. Growth characteristics include retarded physical growth.
Complications
Complications can include the following:
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Mental retardation
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Delayed development of physical skills
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Blindness
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Deafness
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Progressive deterioration (Niemann-Pick disease [NPD] is a fatal disorder.)
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Autosomal recessive inheritance pattern.
