One of the lysosomal storage diseases is Neimann-pick disease (NPD) which is characterized by acid sphingomyelinase deficiency (ASMD). To clarify, ASMD is a catalyser that acts on the hydrolysis reaction of sphingomyelin (SM) into phosphocoline and ceramide. Therefore, lysosomes such as macrophages are piled up with both SM and its precursor leading to hepatosplenomegaly, pulmonary disease, cytopenias, and neurologic problems.
NPD is of 4 types:
-Type A: This type is fatal for infants of less than 3 years old. Indeed, it shows very low acid sphingomyelinase activity that impairs growth and nervous system function shortage. Besides, the average life expectancy is 18 months.
-Type B: it is concerned with visceral (hepatosplenomegaly, thrombocytopenia and interstitial lung disease) and some neurological symptoms. Some patients live up to mid teens or adulthood.
-Type C or NPC: Specifically occurs in adults but doesn’t deny the fact that it occurs at any age. Neurologic, systemic and psychiatrist problems are the main concerns of NPC. For children, early stages of having NPC shows jaundice, hepatosplenomegaly, splenomegaly and later shows neurological symptoms. Meanwhile, 50% of adults having NPC shows minimal or no hepatosplenomegaly, so isolated splenomegaly prevails.
-Type D: The less variant NPD occurs in adulthood.
Treatment of Neimann-pick:
-For type A and B: no proper treatment has been reported due to severity of the disease.
-For type C: Zavesca (Misglustat), and it slows down the neurological symptoms and disease development for some patients, but its not a cure. However, the national institute of health (NIH) and Therapies for Rare and Neglected diseases (TRND) have started human trials (2 patients from USA) to test cyclodextrin efficacy in fixing cholesterol fluctuation; thus, it acts on reducing neurodegeneration and increasing average life expectancy for patients.
There is hope for patients with the mild phenotype of the disease. In fact, an infant with Neimann-Pick C disease suffering from multisystem organ failure has succeeded in maintaining normal neurological outcomes five years after liver transplant.
References:
-Bajwa H, Azhar W. Niemann-Pick Disease. 2021 Jul 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 32310589
-Lemoine CP, Superina R, Mohammas S. Normal long-term neurologic and graft outcome after liver transplantation in an infant with Neimann-Pick type C disease. Am J Transplant. 2021 Aug 29. doi: 10.1111/ajt.16819. Epub ahead of print. PMID: 34455703.
