Induced Pluripotent Stem Cells for Niemann Pick Disease
Condition: Niemann-Pick Diseases
MeSH terms: Pick Disease of the Brain; Aphasia, Primary Progressive; Frontotemporal Dementia; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
Study type: Observational

Summary: 
      Establishment of individualized human cellular disease models based on induced pluripotent
      stem cells that reflect the broad heterogeneous phenotypic spectrum of Niemann Pick disease
    

Detailed description: 
      Niemann-Pick disease type C (NPC) is a lipid storage disease that can present in infants,
      children, or adults. Neonates can present with ascites and severe liver disease from
      infiltration of the liver and/or respiratory failure from infiltration of the lungs. Other
      infants, without liver or pulmonary disease, have hypotonia and developmental delay. The
      classic presentation occurs in mid-to-late childhood with the insidious onset of ataxia,
      vertical supranuclear gaze palsy, and dementia. Dystonia and seizures are common. Dysarthria
      and dysphagia eventually become disabling, making oral feeding impossible; death usually
      occurs in the late second or third decade from aspiration pneumonia. Adults are more likely
      to present with dementia or psychiatric symptoms. The diagnosis of NPC is confirmed by
      biochemical testing that demonstrates impaired cholesterol esterification and positive
      filipin staining in cultured fibroblasts. Biochemical testing for carrier status is
      unreliable. Most individuals with NPC have NPC1, caused by mutations in the NPC1 gene; fewer
      than 20 individuals have been diagnosed with NPC2, caused by mutations in the NPC2 gene.
      Molecular genetic testing of the NPC1 genes detects disease-causing mutations in
      approximately 94% of individuals with NPC. Such testing is available clinically.

      NPC is inherited in an autosomal recessive manner. The phenotype (i.e., age of onset and
      severity of symptoms) usually runs true in families. Carrier testing for at-risk relatives
      and prenatal testing for pregnancies at increased risk are possible when the two
      disease-causing mutations have been identified in the family.

      Though NPC is a pan-ethnic disorder, the prevalence of this autosomal-recessive disorder is
      elevated in countries with a higher frequency of consanguinity.

      Therefore, the goal of the study to prepare a cell culture from patients affected with
      Niemann Pick disease in order to identify novel pathways and proteins involved in disease
      progression that allow for an earlier diagnosis (i.e. before symptom onset) and that are
      suitable targets for an individualized therapeutic approach able to address not only the
      hepatic form, but also the neurologic form of the disease, which is less responsive to the
      current therapeutic approaches.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The patient has a diagnosis of Niemann Pick disease
      
Biospecimen description: 
      The skin biopsy will be carried out for patients with a diagnosis of Niemann Pick. The biopsy
      is performed by the physician by means of punch biopsy (diameter 2-3 mm) under local
      anesthesia, preferably on the forearm (alternatively: thigh). The biopsy is immediately
      transferred to sterile cell culture medium and sent by center representative for the quickest
      possible processing to CENTOGENE's laboratory located in Germany or to professional
      collaborators being part of the project.