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Niemann-Pick disease, type C2(NPC2)

MedGen UID:
335942
Concept ID:
C1843366
Disease or Syndrome
Synonym: NPC2
 
Gene (location): NPC2 (14q24.3)
 
Monarch Initiative: MONDO:0011873
OMIM®: 607625

Disease characteristics

Excerpted from the GeneReview: Niemann-Pick Disease Type C
Niemann-Pick disease type C (NPC) is a slowly progressive lysosomal disorder whose principal manifestations are age dependent. The manifestations in the perinatal period and infancy are predominantly visceral, with hepatosplenomegaly, jaundice, and (in some instances) pulmonary infiltrates. From late infancy onward, the presentation is dominated by neurologic manifestations. The youngest children may present with hypotonia and developmental delay, with the subsequent emergence of ataxia, dysarthria, dysphagia, and, in some individuals, epileptic seizures, dystonia, and gelastic cataplexy. Although cognitive impairment may be subtle at first, it eventually becomes apparent that affected individuals have a progressive dementia. Older teenagers and young adults may present predominantly with apparent early-onset dementia or psychiatric manifestations; however, careful examination usually identifies typical neurologic signs. [from GeneReviews]
Authors:
Marc Patterson   view full author information

Additional descriptions

From OMIM
Niemann-Pick disease type C (NPC) is an autosomal recessive lipid storage disorder characterized by progressive neurodegeneration. Approximately 95% of cases are caused by mutations in the NPC1 gene (607623), referred to as type C1 (257220); 5% are caused by mutations in the NPC2 gene (601015), referred to as type C2. The clinical manifestations of types C1 and C2 are similar because the respective genes are both involved in egress of lipids, particularly cholesterol, from late endosomes or lysosomes (summary by Vance, 2006).  http://www.omim.org/entry/607625
From MedlinePlus Genetics
Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood.

Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the basis of genetic cause and the signs and symptoms of the condition.

The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.

Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.  https://medlineplus.gov/genetics/condition/niemann-pick-disease

Clinical features

From HPO
Foam cells
MedGen UID:
924121
Concept ID:
C4281786
Finding
The presence of foam cells, a type of macrophage that localizes to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance.
CNS foam cells
MedGen UID:
1813072
Concept ID:
C5558248
Finding
The presence of foam cells, a type of macrophage that localizes to fatty deposits on blood vessel walls, in the central nervous system.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Prolonged neonatal jaundice
MedGen UID:
347108
Concept ID:
C1859236
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Cataplexy
MedGen UID:
2862
Concept ID:
C0007384
Disease or Syndrome
A sudden and transient episode of bilateral loss of muscle tone, often triggered by emotions.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
Neurofibrillary tangles
MedGen UID:
39273
Concept ID:
C0085400
Finding
Pathological protein aggregates formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate in an insoluble form.
Perseverative thought
MedGen UID:
66686
Concept ID:
C0233651
Mental or Behavioral Dysfunction
Manifestations of perseverative thoughts are behaviors that do not meet the demands of the situation, are not the product of deliberation, and may unfold despite counter intention.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Loss of speech
MedGen UID:
107445
Concept ID:
C0542223
Finding
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Pulmonary fibrosis
MedGen UID:
11028
Concept ID:
C0034069
Disease or Syndrome
Replacement of normal lung tissues by fibroblasts and collagen.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Sea-blue histiocyte syndrome
MedGen UID:
19908
Concept ID:
C0036489
Disease or Syndrome
An abnormality of histiocytes, in which the cells take on a sea blue appearance due to abnormally increased lipid content. Histiocytes are a type of macrophage. Sea-blue histiocytes are typically large macrophages from 20 to 60 micrometers in diameter with a single eccentric nucleus whose cytoplasm if packed with sea-blue or blue-green granules when stained with Wright-Giemsa.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Bone-marrow foam cells
MedGen UID:
383940
Concept ID:
C1856560
Finding
The presence of foam cells in the bone marrow, generally demonstrated by bone-marrow aspiration or biopsy. Foam cells have a vacuolated appearance due to the presence of complex lipid deposits, giving them a foamy or soap-suds appearance.
Low cholesterol esterification rate
MedGen UID:
335943
Concept ID:
C1843371
Finding
A reduction in the rate of cholesterol esterification.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Fetal ascites
MedGen UID:
226930
Concept ID:
C1285291
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity during the fetal period.
Vertical supranuclear gaze palsy
MedGen UID:
334385
Concept ID:
C1843369
Disease or Syndrome
A supranuclear gaze palsy is an inability to look in a vertical direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.

Professional guidelines

PubMed

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Diagnosis

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