Medical Care
The first disease-specific enzyme replacement treatment for non-CNS ASMD, olipudase alfa, was approved by the FDA in August 2022.
Other medical and surgical care for Niemann-Pick disease (NPD) types A and B are mainly focused on supportive care.
Adult patients with elevated serum cholesterol due to NPD type B should be treated to bring serum cholesterol concentration into the normal range. Liver function should be monitored in patients treated with statins.
Transfusion of blood products may be necessary for acute episodes of bleeding secondary to hypersplenism and thrombocytopenia in NPD type B patients.
Supplemental oxygen may be used for NPD type B patients with symptomatic interstitial lung disease. Bronchopulmonary lavage has had variable results.
Olipudase alfa
Olipudase alfa is an ASM enzyme that the FDA has approved for the treatment of non-CNS manifestations of ASMD in adult and pediatric patients. Approval of olipudase alfa arose from the ASCEND and ASCEND-Peds trials. The ASCEND trial assessed 31 adults with ASMD type A/B or type B, including their lungs’ percent predicted diffusing capacity for carbon monoxide, as well as spleen volume. The olipudase alfa group demonstrated improved lung function and reduced splenomegaly compared with the placebo group from baseline to week 52 (increase in predicted diffusing capacity for carbon monoxide 22% vs 3%, respectively; spleen volume 39% decrease vs 0.5% increase, respectively). [19] In the ASCEND-Peds trial, nine patients treated with olipudase alfa who were able to perform the baseline test for diffusing capacity for carbon monoxide saw improvement in lung performance from baseline to week 52 (mean increase of 33% for predicted diffusing capacity for carbon monoxide). [20]
Surgical Care
Orthotopic liver transplantation in an infant with Niemann-Pick disease (NPD) type A and amniotic cell transplantation in several patients with NPD type B have been attempted with little or no success.
Bone marrow transplantation has been attempted in patients with NPD type B with variable results, including reduction in spleen and liver volumes, increased peripheral blood cell counts, and decreased infiltration of the lungs. It is not considered appropriate for treatment of NPD with neurologic involvement.
Histocompatible hematopoietic stem cell transplantation conducted on a 4-year-old girl with NPD type B was successful in improving sphingomyelinase enzyme levels and improving severe pulmonary disease. [21]
To date, lung transplantation has not been performed in any patient with type B disease who was severely compromised.
Although patients may have massive splenomegaly, splenectomy should be avoided whenever possible. Removal of the spleen is accompanied by deterioration of pulmonary status and increased morbidity since it eliminates an important reservoir for substrate accumulation that leads to acceleration of disease in other organs such as the lung. [22]
Further Care
Pulmonary infections occur frequently in patients with Niemann-Pick disease (NPD) types A and B.
Patients with type A disease may develop respiratory decompensation, requiring inpatient care for stabilization during severe episodes.
Diet
Pediatric patients with NPD type B require frequent meals to promote growth. Many patients have early satiety because of organomegaly. For some patients, supplements with high levels of kilojoules are useful.
In patients with NPD type A, feeding becomes a major difficulty as the disease progresses. Discussion with the family to determine a strategy for providing calories should occur.
Activity
Patients with NPD type B disease and splenomegaly should avoid contact sports because of the risk of splenic rupture. Immediate medical attention should be obtained after trauma, owing to the risk of splenic rupture and intracranial bleeding due to hypersplenism.
Consultations
Evaluation and ongoing care by a trained metabolic geneticist should occur.
Patients with NPD type B should undergo annual pulmonary function testing and evaluation.
-
Autosomal recessive inheritance pattern.
-
Role of acid sphingomyelinase in metabolism pathways inside cellular organelles.
