Neonatal and infantile presentations of NPC are most commonly nonspecific and may go unrecognized. [centogene.com]

From late infancy onward, the presentation is dominated by neurologic manifestations. [ncbi.nlm.nih.gov]

[…] disease Also disorders with massive cell destruction that overloads body's capacity to digest lipids ( thalassemia, sickle cell anemia, ITP, chronic renal failure ) Type A Definition / general : Acute neuronopathic form Most common type Occurs in infants Presents [pathologyoutlines.com]

NPD-C has a variable age of presentation, ranging for the neonatal period into adulthood. hepatobiliary signs and symptoms 2 neonatal presentation: cholestatic liver failure infancy and childhood presentation: hepatosplenomegaly neurological signs and [radiopaedia.org]

Type A Niemann-Pick disease usually presents symptoms within months of birth. [medium.com]

• Disability

  As the condition progresses, affected children develop learning disabilities, psychological problems, dementia, and often lose the ability to speak. [myriad.com]

  Bone-marrow foam cells Sea-blue histiocyte syndrome Splenomegaly Abnormality of the musculoskeletal system Hypotonia Abnormality of the nervous system Cataplexy Cerebellar ataxia Dementia Dysarthria Dystonic disorder Global developmental delay Intellectual disability [ncbi.nlm.nih.gov]

  0002015 Dystonia 0001332 Fetal ascites 0001791 Foam cells in visceral organs and CNS 0003640 Generalized hypotonia Decreased muscle tone Low muscle tone [ more ] 0001290 Global developmental delay 0001263 Hepatomegaly Enlarged liver 0002240 Intellectual disability [rarediseases.info.nih.gov]

• Ascites

  In rare cases, an ultrasound examination close to the natural end of pregnancy could result in detection of fetal ascites; infants thus identified typically have severe neonatal liver disease with jaundice and persistent ascites. [centogene.com]

  Resources Molecular Genetics Chapter Notes References Authors: Marc Patterson view full author information Show allHide all Abnormality of metabolism/homeostasis Low cholesterol esterification rate Abnormality of prenatal development or birth Fetal ascites [ncbi.nlm.nih.gov]

  Cataplexy 0002524 Dementia Dementia, progressive Progressive dementia [ more ] 0000726 Dysarthria Difficulty articulating speech 0001260 Dysphagia Poor swallowing Swallowing difficulties Swallowing difficulty [ more ] 0002015 Dystonia 0001332 Fetal ascites [rarediseases.info.nih.gov]

• Recurrent Respiratory Infection

  respiratory infections Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ] 0002205 Rigidity Muscle rigidity 0002063 Sea-blue histiocytosis 0001982 Short stature [rarediseases.info.nih.gov]

  At the age of 1 year, splenomegaly was noted and interstitial peribronchial attenuation found in a chest X-ray that was taken because of recurrent respiratory infections. [academic.oup.com]

• Difficulty Walking

  Niemann-Pick care at Mayo Clinic Symptoms Niemann-Pick signs and symptoms may include: Clumsiness and difficulty walking Excessive muscle contractions (dystonia) or eye movements Sleep disturbances Difficulty swallowing and eating Recurrent pneumonia [mayoclinic.org]

• Splenomegaly

  Common symptoms include hepatomegaly, splenomegaly, jaundice and vertical supranuclear gaze palsy (VSGP). 95% of NPC patients will have mutations in the NPC1 gene. [mangen.co.uk]

  […] cells Foam cells Abnormality of the digestive system Dysphagia Hepatomegaly Jaundice Prolonged neonatal jaundice Abnormality of the eye Vertical supranuclear gaze palsy Abnormality of the immune system Bone-marrow foam cells Sea-blue histiocyte syndrome Splenomegaly [ncbi.nlm.nih.gov]

  The same cells involving the alveoli are associated with ground-glass opacities. 2, 13, 15, 24 Hepatosplenomegaly is the most important clinical finding in NPD type B, 11, 25 with splenomegaly being more marked than hepatomegaly. 6, 11 Splenomegaly may [scielo.br]

  […] in newborn 0006579 Psychosis 0000709 Respiratory failure 0002878 Respiratory insufficiency Respiratory impairment 0002093 Sea-blue histiocytosis 0001982 Seizures Seizure 0001250 Spasticity Involuntary muscle stiffness, contraction, or spasm 0001257 Splenomegaly [rarediseases.info.nih.gov]

• Diarrhea

  Mice given oral miglustat at doses of 210 (16 times the human dose), 420 and 840/500 mg/kg/day developed diarrhea, abdominal swelling and rectal prolapse. Microscopic examination of the large intestine showed inflammatory lesions. [parseghianfund.nd.edu]

• Hepatosplenomegaly

  Disease, Type A Type B Definition / general : Chronic form (visceral form) without nervous system involvement Highest incidence in those of Turkish, Arabic and North African descent Uncommon in Ashkenazi Jews ( Am J Hum Genet 2002;71:1413 ) Onset of hepatosplenomegaly [pathologyoutlines.com]

  All patients had hepatosplenomegaly, which was painless in 6 (46.1%). Eight (61.5%) had had hepatosplenomegaly since childhood. From a respiratory standpoint, 8 patients (61.5%) were asymptomatic, and 5 (38.4%) had dyspnea. [scielo.br]

  Neimann-Pick disease type C2 may be characterized by ataxia (difficulty coordinating movements), vertical supranuclear gaze palsy (inability to move the eyes vertically), poor muscle tone, hepatosplenomegaly (enlarged liver and spleen), interstitial lung [monarchinitiative.org]

  NPD-C has a variable age of presentation, ranging for the neonatal period into adulthood. hepatobiliary signs and symptoms 2 neonatal presentation: cholestatic liver failure infancy and childhood presentation: hepatosplenomegaly neurological signs and [radiopaedia.org]

  Nieman-pick types Niemann-Pick disease type A (neurological type) The symptoms include: hepatosplenomegaly (an enlarged liver and spleen), failure to thrive (gain weight and grow at the expected rate) progressive (getting worse over time) deterioration [contact.org.uk]

• Macula

  Showing of 30 | 30%-79% of people have these symptoms Cherry red spot of the macula 0010729 Percent of people who have these symptoms is not available through HPO Athetosis Involuntary writhing movements in fingers, hands, toes, and feet 0002305 Autosomal [rarediseases.info.nih.gov]

  […] with the following: hepatosplenomegaly — swelling of the liver and spleen low blood platelet count unsteady gait or slurred speech difficulties swallowing that can lead to malnourishment (dysphagia) muscular spasms lung damage cherry red spot on the macula [wideacademy.co]

• Hydrops Fetalis

  There were no signs of placentomegaly or hydrops fetalis. [frontiersin.org]

• Vertical Gaze Palsy

  gaze palsy, cognitive impairment (e.g. poor school performance) adolescent and adult presentation: ataxia, supranuclear vertical gaze palsy, psychiatric illnesses, cognitive impairment Radiographic features are limited, and MRI is the modality of choice [radiopaedia.org]

  gaze palsy in all patients presenting with a psychotic illness. [touchneurology.com]

  Vertical gaze palsy (the inability to move the eyes up and down), enlarged liver, enlarged spleen, or jaundice in young children are strong indications that NPC should be considered. [nnpdf.org]

  […] supranuclear gaze palsy, gelastic cataplexy, seizures, and dementia. [nature.com]

• Vertical Supranuclear Ophthalmoplegia

  supranuclear ophthalmoplegia, Niemann-Pick disease type D, Niemann-Pick disease Nova Scotian type Niemann-Pick disease (NPD) is a lipid storage disorder that results from the deficiency of a lysosomal enzyme, acid sphingomyelinase. [centogene.com]

  An initial psychotic disease can sometimes precede the onset of any motor symptoms by up to 10 years. 3 While most, if not all, adult patients show difficulties in vertical gaze (vertical supranuclear ophthalmoplegia) at disease onset, NPC remains heterogeneous [touchneurology.com]

Papandreou A, Gissen P: Diagnostic workup and management of patients with suspected Niemann-Pick type C disease. Therapeutic advances in neurological disorders 2016;9(3):216-229. [rarediseases.org]

• Hypercholesterolemia

  […] histologic) description Clusters and individual foam cells up to 90 microns Cytoplasm has clear vacuoles of varying size, may be mulberry or soap bubble-like Nuclei are small and round with coarse chromatin Differential diagnosis Similar foam cells in hypercholesterolemia [pathologyoutlines.com]

  Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia. J Biol Chem. 2005; 280 :12710-20 8. Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA. et al. [jcancer.org]

Treatment & Management No specific treatment is known for type A and B, but symptoms are treated. [ordindia.org]

Treatment with anticonvulsants and more recent disease specific treatments as Miglustat or hydroxypropyl-β-cyclodextrin have showed a variable response. [content.iospress.com]

Several treatment options, including bone marrow transplants, enzyme replacement therapy, and gene therapy have been used. Research is ongoing to determine the effectiveness of such treatments. [omicsonline.org]

In 2006, Jiang et al., summarized that decreased serum levels of cholesterol and apoAI may indicate a poor prognosis [ 21 ]. [jcancer.org]

The prognosis for people with Type C Niemann-Pick disease varies, with some who are less severely affected living well into adulthood. [medium.com]

What is the prognosis for an individual with Niemann-Pick Disease Type C2? Niemann-Pick disease type C shows variable disease advancement, with an earlier onset associated with faster disease progression. [myriad.com]

[…] general : Chronic form (visceral form) without nervous system involvement Highest incidence in those of Turkish, Arabic and North African descent Uncommon in Ashkenazi Jews ( Am J Hum Genet 2002;71:1413 ) Onset of hepatosplenomegaly in preteen years Good prognosis [pathologyoutlines.com]

Prognosis  Type A: Most (approx. 85%) cases being fatal by 18 months. [de.slideshare.net]

Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder of unknown etiology characterized by defective egress of cholesterol from lysosomes [5]. [wikigenes.org]

The association of diffuse pulmonary infiltration and hepatosplenomegaly can be observed in a number of diseases of varying etiologies, such as infectious diseases (tuberculosis, fungal diseases, malaria, and schistosomiasis), neoplastic diseases (lymphoma [scielo.br]

Niemann-Pick disease type C (NP-C) Ataxia Ataxia is a common but nonspecific sign of NP-C. 4, 23, 24 Early-onset ataxia, ataxia in combination with other clinical symptoms 25 (“ataxia plus”; see table 1 ), ataxia without neuropathy, or ataxia of unknown etiology [cp.neurology.org]

[…] characterised by mental retardation, seizures and often rapid neurodegeneration, in adults the disease is characterised by slow cognitive decline, major neuropsychiatric illness and the development of ataxia and dystonia. 1 The data are limited in terms of the epidemiology [touchneurology.com]

The objectives of the present study were to describe the most common HRCT findings and the major clinical and epidemiological characteristics observed in these patients. [scielo.br]

Discussed topics • Introduction • History • Types • Prognosis • Incidence • Causes • Pathophysiology • Mechanism of Cholesterol Trafficking • Signs and Symptoms • Diagnosis • Treatment • Prevention • Research Direction 2 3. [de.slideshare.net]

The pathophysiology and mechanisms of NP-C disease. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):83-7. Review. Vance JE. Lipid imbalance in the neurological disorder, Niemann-Pick C disease. FEBS Lett. 2006 Oct 9;580(23):5518-24. Epub 2006 Jun 15. [ghr.nlm.nih.gov]

The pathophysiology and mechanisms of NP-C disease. Biochim Biophys Acta. 2004 Oct 11;1685(1-3):83-7. Review. Citation on PubMed Vance JE. Lipid imbalance in the neurological disorder, Niemann-Pick C disease. FEBS Lett. 2006 Oct 9;580(23):5518-24. [medlineplus.gov]

A better understanding of the underlying pathophysiology of NPC will allow for the development of more targeted treatments to join miglustat in the armamentarium of tools available for treating NPC. [touchneurology.com]

Metab. (2005) [Pubmed] The pathophysiology and mechanisms of NP-C disease. Sturley, S.L., Patterson, M.C., Balch, W., Liscum, L. Biochim. Biophys. [wikigenes.org]

Good pulmonary hygiene is important and precautions should be taken to prevent aspiration. References References Verot L, Chikh K, Freydi?(r)re E, Honor?(c) R, Vanier MT, Millat G. [disorders.eyes.arizona.edu]

Miglustat is classified as an enzyme inhibitor, and works by preventing the body from producing fatty substances (in the case of type C, cholesterol) so that less of it will build up in the body. [omicsonline.org]

Chest physiotherapy and antibiotics may help to prevent regular lung infections. Individuals with the condition need a gastronomy tube for feeding when they can no longer swallow well enough to avoid choking or malnutrition. [myriad.com]

Mutations in these genes lead to a shortage of functional protein, which prevents movement of cholesterol and other lipids, leading to their accumulation in cells. [medicinenet.com]

Discussed topics • Introduction • History • Types • Prognosis • Incidence • Causes • Pathophysiology • Mechanism of Cholesterol Trafficking • Signs and Symptoms • Diagnosis • Treatment • Prevention • Research Direction 2 3. [de.slideshare.net]