Rare forms of interstitial lung disease
Muhunthan Thillai, David R Moller, Keith C Meyer in Clinical Handbook of Interstitial Lung Disease, 2017
Niemann–Pick disease is a group of disorders characterized by accumulation of sphingomyelin, and it is inherited in an autosomal recessive pattern. These disorders are caused by mutations in the sphingomyelin phosphodiesterase-1 gene or genes that control cellular processing and transport of low-density cholesterol. Intracellular accumulation of sphingomyelin or unesterified cholesterol leads to disease manifestations that commonly include organomegaly and neurologic deficits with variable age of onset. ILD due to parenchymal accumulation of lipid-laden macrophages, alveolar proteinosis, recurrent respiratory infections and respiratory failure can occur in these patients (139,150–153). At present, there is no cure or enzyme replacement therapy for Niemann–Pick disease.
Histiocytosis and Lipid Storage Diseases
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
Type C Niemann-Pick disease, which is under type 2 in the new classification system, has almost normal sphingomyelinase activity. It is considered to be a cholesterol lipidosis secondary to defective intracellular cholesterol transport and is a quite distinct entity from types A and B. Adult onset with splenomegaly in an otherwise healthy person, as in this case, is not uncommon in type C Niemann-Pick disease. Typical Niemann-Pick disease is an affliction of infancy. These infants during their first months of life gain weight poorly, and have developmental delays. During their second year the child is usually flaccid, with huge hepatosplenomegaly, lymphadenopathy, and skin and bone lesions. The typical disease has been designated as type A.
Lysosomal, sterol and lipid disorders
Steve Hannigan in Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
The disorder is diagnosed by demonstration of reduced or absent enzyme activity in white blood cells and ibroblasts cultured from skin. Prenatal diagnosis and screening for carriers are available. Treatment for individuals with Niemann-Pick disease aims to provide relief of any symptoms and support in the care of the child. Genetic counselling may be of beneit to individuals afected by this disorder.
Chronic interstitial lung diseases in children: diagnosis approaches
Published in Expert Review of Respiratory Medicine, 2018
Nadia Nathan, Laura Berdah, Keren Borensztajn, Annick Clement
Several metabolic disorders can be associated with ILD. Among them, Gaucher’s disease, an autosomal recessive disease is the most common lysosomal storage diseases. It is caused by a genetic deficiency of the gluco-cerebrosidase lysosomal enzyme that catalyzes the breakdown of glucocerebroside, a cell membrane constituent of red and white blood cells. Niemann-Pick diseases (A, B, C) are rare genetic diseases primarily due to deficiency of sphingomyelinase resulting in the accumulation of sphingomyelin within lysosomes in the macrophage-monocyte phagocyte systems of multiple organs, mainly the brain, spleen, liver, lung, and bone marrow. Histology demonstrates lipid laden macrophages in the marrow, as well as ‘sea-blue histiocytes’ on pathology [48]. Hermansky-Pudlak syndrome is a heterogeneous group of autosomal recessive disorders associated with accumulation of a ceroid-like substance in lysosomes of a variety of tissues. It is characterized by albinism, bleeding tendency associated to poor platelet aggregation, and systemic complications associated to lysosomal dysfunction [49].
Psychiatric and neurological symptoms in patients with Niemann-Pick disease type C (NP-C): Findings from the International NPC Registry
Published in The World Journal of Biological Psychiatry, 2019
Olivier Bonnot, Clarissa S. Gama, Eugen Mengel, Mercè Pineda, Marie T. Vanier, Louise Watson, Marie Watissée, Barbara Schwierin, Marc C. Patterson
Niemann-Pick disease type C (NP-C) is a rare, pan-ethnic metabolic disease caused by autosomal recessive inheritance of mutations in the NPC1 gene or the NPC2 gene (Carstea et al. 1997; Naureckiene et al. 2000), and has been estimated to affect 1 in 89,000 pregnancies (Wassif et al. 2016). NP-C is characterised by progressive neurodegeneration and early mortality (Wraith et al. 2009; Vanier 2010; Walterfang et al. 2012; Imrie et al. 2015). It is one of a number of inborn errors of metabolism that are associated with psychiatric symptoms, and which should be considered by clinical psychiatrists as possible causes of organic psychiatric disease (Klünemann et al. 2012; Bonnot et al. 2014; Nia 2014).
Designation of orphan conditions in Europe: regulatory observations and considerations after implementation of regulation 141/2000
Published in Expert Opinion on Orphan Drugs, 2020
Segundo Mariz, Kerstin Westermark, Bruno Sepodes
In some instances, the COMP may opt to stop clustering by type. Niemann Pick disease which is a metabolic disorder involving three clinical types has been designated 5 times as Niemann-Pick Type C and more recently 3 times as Niemann-Pick. This would mean a total of eight designations have clustered around the term Niemann-Pick showing some interest in developing a medicine in this condition [12]. Another condition which became broader recently was spinal muscular atrophy which previously was designated 5q spinal muscular atrophy. The broadening of conditions can be changed into ”umbrella” terms which stay not above 5 in 10,000 can occur with the arrival of new submissions for a previous condition designated such 5q spinal muscular atrophy. In some instances such as the indication of ”treatment in hematopoietic stem cell transplantation the COMP has made a regulatory effort to bring previous smaller conditions such as ”adjunctive treatment in hematopoietic cell transplantation” under this umbrella term. Thus, the aim maybe driven by regulatory considerations or due to changes in the classification system such as those seen for hematopoietic malignancies where the WHO published a revised classification system creating a new system which the COMP need to adapt to. Previous designations such as ”treatment of hairy cell leukemia” which were designated before 2008 were subsequently designated as ”Treatment of Chronic Lymphoblastic Leukemia” since the change. While these kinds of changes do not appear to affect the overall grouping a trend by therapeutic area, the measuring of clustering by condition becomes more fragmented making the overall picture for some conditions difficult to establish. Also, of note is the possibility of a condition changing at the time of submission for marketing authorization of an orphan designated product. The earlier designation of interstitial cystitis as a distinct condition with a prevalence of not more than 5 in 10,000 was revised to bladder pain syndrome following a revision of the classification of these disorders published in 2015. As this occurred during the review for the maintenance of the orphan designation and the prevalence went over 5 in 10,000 the applicant could no longer satisfy the criteria for the maintenance of the orphan designation at the time or marketing authorization and had to withdraw the designation.
Related Knowledge Centers
- Acid Sphingomyelinase
- Hepatosplenomegaly
- Metabolic Disorder
- Sphingolipid
- Sphingolipidoses
- Sphingomyelin
- Splenomegaly
- Lysosome
- Niemann–Pick Disease, Type C
- Lysosomal Storage Disease