Niemann-Pick disease

Classification according to ICD-10
E75.2	Other sphingolipidoses (including Niemann-Pick disease)
ICD-10 online (WHO version 2019)

The Niemann-Pick disease , which is also known as Niemann-Pick disease , Niemann-Pick syndrome or sphingomyelin lipidosis , belongs to the group of sphingolipidoses , which in turn are counted among the lysosomal storage diseases . It is a rare genetic disease that autosomal - recessive inherited. This is due to a genetic defect in the enzyme sphingomyelinase . The enzyme defect leads to the storage of sphingomyelin in the lysosomes of the liver, spleen, bone marrow and brain.

The disease is named after Albert Niemann (1880–1921) and Ludwig Pick (1868–1944).

to form

Although the first description of the syndrome by Albert Niemann in 1914 consisted only of the clinical appearance and the histological findings of reticuloendotheliosis, numerous forms have now been differentiated due to advances in human genetics . The most important are:

Type IA (formerly type A - acute infantile neuropathic form):

Onset at 3–4 months of age with poor drinking and dystrophy . The main symptom is hepatosplenomegaly (with a focus on hepatomegaly ). In addition, palpable lymph nodes and brownish discoloration of the skin are common. Neurological degradation occurs in the second year of life with loss of social contact, deafness, blindness and spasticity. A macular mark is found in around 50% of patients . The disease is always unfavorable , death usually occurs within 2 years. This is the most common form.

Type IS (formerly type B - chronic visceral form):

Mild course with hepatomegaly and lung involvement (infiltrates) in childhood. There is no CNS involvement. The life expectancy of this type is only slightly restricted.

Type C (Niemann-Pick type C disease; NPC) - changed gene to 95% NPC 1; to 5% NPC 2:

Whereby NPC 1 and NPC 2 are genes that encode proteins that are responsible for intracellular cholesterol transport. Clinical symptoms: neonatal jaundice , supranuclear palsy, and cerebellar ataxia . The beginning is very variable, both in infants, children, as well as in adolescence or adulthood. For a few years, drug therapy has been available that delays progression.

Diagnostics and therapy

There is evidence that certain cyclodextrins can improve symptoms of this rare genetic disorder. Cyclodextrins are sugar-like substances that are used, among other things, to solubilize drugs. Type C is treated with miglustat.

research

Loss of myelin in the central nervous system is seen as one of the most important factors in the pathogenesis of Niemann-Pick disease. Animal models that carry mutations on which Niemann-Pick disease is based, for example a mutation in the NPC1 gene as found in Niemann-Pick type C, are used to research the disease . In this model it could be shown that the expression of the protein Myelin Gene Regulatory Factor (MRF) decreases significantly. MRF is a transcription factor of critical importance in the formation and maintenance of myelin sheaths . It is therefore likely that errors in the differentiation of oligodendrocytes and in myelination cause the neurological deficits.

Individual evidence

↑ B. Liu et al .: Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1 - / - mouse. In: PNAS (2009) 106 (7), pp. 2377-2382. PMID 19171898 (see also reports in The Scientist 1 & 2 (requires free registration))
^ ^A ^b X. Yan, J. Lukas, M. Witt, Andreas Wree , R. Hubner, M. Frech, R. Kohling, A. Rolfs, J. Luo: Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse . In: Metab Brain Dis . tape 26 , no. 4 , September 2011, p. 299-306 , doi : 10.1007 / s11011-011-9263-9 , PMID 21938520 .
↑ Matthias Koenning, Stacey Jackson, Curtis M. Hay, Clare Faux, Trevor J. Kilpatrick, Melanie Willingham, Ben Emery: Myelin Gene Regulatory Factor Is Required for Maintenance of myelin and Mature Oligodendrocyte Identity in the adult CNS . In: The Journal of Neuroscience . tape 32 , no. 36 , September 2012, p. 12528-12542 , doi : 10.1523 / jneurosci.1069-12.2012 , PMID 22956843 .

[Ghannoum-1] B. Liu et al .: Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1 - / - mouse. In: PNAS (2009) 106 (7), pp. 2377-2382. PMID 19171898 (see also reports in The Scientist 1 & 2 (requires free registration))

[yan-2] A ^b X. Yan, J. Lukas, M. Witt, Andreas Wree , R. Hubner, M. Frech, R. Kohling, A. Rolfs, J. Luo: Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse . In: Metab Brain Dis . tape 26 , no. 4 , September 2011, p. 299-306 , doi : 10.1007 / s11011-011-9263-9 , PMID 21938520 .

[koenning-3] Matthias Koenning, Stacey Jackson, Curtis M. Hay, Clare Faux, Trevor J. Kilpatrick, Melanie Willingham, Ben Emery: Myelin Gene Regulatory Factor Is Required for Maintenance of myelin and Mature Oligodendrocyte Identity in the adult CNS . In: The Journal of Neuroscience . tape 32 , no. 36 , September 2012, p. 12528-12542 , doi : 10.1523 / jneurosci.1069-12.2012 , PMID 22956843 .