The case suggests lung transplantation can be a feasible option for patients with lung involvement.
A new case report is adding complexity to scientists’ understanding of a rare lysosomal storage disorder, Niemann-Pick disease type B (NPDB), an autosomal recessive disease caused by mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.
In this new report, investigators describe a case in which a patient with bilateral cystic bronchiectasis received a NPDB diagnosis following the surgery, suggesting a novel phenotype of the disease. The report was published in Chest.
Niemann-Pick disease (NPD) has 2 distinct phenotypes. Type A occurs in infancy and is typically fatal, the authors explained. Conversely, type B does not occur until adulthood and is usually associated with respiratory involvement and hepatosplenomegaly.
“The pathologic hallmark is the intracellular accumulation of sphingomyelin in affected tissues (liver, spleen, lungs, bone marrow, brain) that results in large clusters of foamy lipid-laden macrophages in these organs,” they wrote.
Sometimes, the variability associated with lung involvement can make NPD difficult to diagnose, which means some patients may end up needing a lung transplant before a specific diagnosis can be made, the investigators said. In their new case report, they describe a case in which the main clinical manifestation of NPDB was bilateral cystic bronchiectasis.
The case involved a 31-year-old woman without a history of smoking who had hypoxemic respiratory failure and recurrent pulmonary infections. Several tests were performed and diagnoses ruled out. The patient refused a hepatic biopsy and was referred for transplantation, which occurred in November 2018, about 2 years after she first sought care at the hospital.
Once the patient’s lungs were removed, her doctors began to see clear signs of a lysosomal storage disorder.
“The histopathologic study demonstrated the presence of bronchiectasis and lung abscesses with multiple clusters of CD68-positive foamy macrophages that were consistent with the pathologic diagnosis of lysosomal storage disease,” the investigators wrote.
An ultrastructural study further showed signs of lysosomal storage disease, and a genetic test soon identified SMPD1 mutation, including a specific variant never before described.
“The singularity of our case lies in the presence of bronchiectasis, an unprecedently described phenotype of NPDB,” the authors wrote. “This finding is accompanied by the detection of a mutation of the SMPD1 gene never previously described (p.Ala461⁄4) and of uncertain meaning.”
The patient was reported to be in good condition 23 months after the procedure, with the authors noting 3 other recent reports have indicated that lung transplantation can be a feasible option for patients with NDPB. They said NDPB can be difficult to diagnose and is believed to be underdiagnosed for that reason. They added that lung manifestations of the disease can be heterogeneous, although the telltale sign is foamy, lipid-laden macrophages in lung tissue.
“The presence of hepatosplenomegaly is a potential contributor to the diagnostic suspicion,” they noted. “As far as functional imaging is concerned, no specific evidence is available. Markers of disease, such as retinal ganglion layers that are potentially recognizable by multimodal imaging, may have both a diagnostic and a monitoring contributing role.”
As far as treatment implications, the authors said improvements in diagnosis could lead to new avenues of therapy and possibly avoid the need for lung transplantation. When transplantation does occur, one important question is whether enzyme replacement therapy would be necessary to protect other organs from damage following transplantation.
Reference
Tirelli C, Arbustini E, Meloni F. Bilateral cystic bronchiectasis as novel phenotype of Niemann-Pick disease type B successfully treated with double lung transplantation. Chest. 2021;159(5):e293-e297. doi:10.1016/j.chest.2020.11.074
Standard Criteria for Loss of Ambulation Needed in DMD
April 19th 2024A recent study suggests the differences between ambulation definitions for patients with Duchenne muscular dystrophy (DMD) can impact the identification of ambulant vs nonambulant individuals, and standard criteria across settings are needed.
Read More
Government agencies have created an online portal for the public to report potential anticompetitive practices in health care; there are changes coming to the “boxed warning” section for chimeric antigen receptor T-cell therapies (CAR T) to highlight T-cell blood cancer risk; questions about the safety of obesity medications during pregnancy have arisen in women on them who previously struggled with fertility issues.
Read More
Gene, Light Therapy Combo Shows Promise Against Prostate Cancer Cells in Proof-of-Concept Study
April 18th 2024In their preclinical model, the researchers found efficacy both in vitro and in vivo by using CRISPR-Cas9 to mimic porphyria and combining the technology with light therapy.
Read More
Pegcetacoplan for PNH More Cost-Effective Than Anti-C5 Monoclonal Antibodies
April 18th 2024A cost-utility analysis conducted from the perspective of the Italian health system found that pegcetacoplan was more effective and less costly than 2 complement 5 (C5) inhibitors for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
Read More