Biochemical and imaging parameters in acid sphingomyelinase deficiency: Potential utility as biomarkers

Abstract

Pick type A/B disease, is a rare lipid storage disorder leading to accumulation of sphingomyelin and its precursors primarily in macrophages. The disease has a broad phenotypic spectrum ranging from a fatal infantile form with severe neurological involvement (the infantile neurovisceral type) to a primarily visceral form with different degrees of pulmonary, liver, spleen and skeletal involvement (the chronic visceral type). With the upcoming possibility of treatment with enzyme replacement therapy, the need for biomarkers that predict or reflect disease progression has increased. Biomarkers should be validated for their use as surrogate markers of clinically relevant endpoints. In this review, clinically important endpoints as well as biochemical and imaging markers of ASMD are discussed and potential new biomarkers are identified. We suggest as the most promising biomarkers that may function as surrogate endpoints in the future: diffusion capacity measured by spirometry, spleen volume, platelet count, low-density lipoprotein cholesterol, liver fibrosis measured with a fibroscan, lysosphingomyelin and walked distance in six minutes. Currently, no biomarkers have been validated. Several plasma markers of lipid-laden cells, fibrosis or inflammation are of high potential as biomarkers and deserve further study. Based upon current guidelines for biomarkers, recommendations for the validation process are provided.Acid Sphingomyelinase Deficiency (ASMD), also known as Niemann-Pick disease types A and B, is a rare lysosomal storage disorder (LSD) caused by mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, leading to strongly decreased activity of acid sphingomyelinase (ASM,. The enzyme ASM is mainly present in lysosomes and catalyzes hydrolysis of sphingomyelin (SM) to ceramide and phosphocholine [5,6] (see Fig. 1). In ASMD, SM and its precursor lipids accumulate in lysosomes, especially in macrophages. These lipid laden macrophages, Niemann-Pick cells, can be found in several tissues, mainly the spleen, liver and lungs [1],

Periodontal condition and treatment in a patient with rare systemic condition: A case report for acid sphingomyelinase deficiency

“…Both diseases are lysosomal storage disorders, and have similar autosomal recessive genetic disturbances with abnormalities in cell signaling pathways. Also, an empirically delayed immune response has been related to a low immunity and the tendency to bleed, and/or changes in coagulation, both conditions due to alterations in bone marrow, which is frequently observed in ASMD and in GD 17,19 . In this context, considering the report of former thrombocytopenia status, oral symptoms, and tooth loss due to lifelong periodontal disease by our ASMD patient, and her medical history of systemic diagnosis and only recent dental treatment, it is suggested that ASMD may have contributed to the establishment of her periodontal disease.…”

“…The available case reports regarding ASMD in the literature focus on patient's systemic conditions without assessment of oral health aspects 17 . To the best of knowledge, this case report provides the first detailed description of the periodontal conditions and the treatment response in a patient with chronic visceral ASMD.…”

The Ophthalmological Manifestations of Various Inborn Errors of Metabolism: A Narrative Review

“…It is a rare genetic disease generated due to sphingomyelinase isoenzymes that affect the body's ability to metabolize cellular cholesterol and lipids. There are 3 types of Niemann-Pick disease, including A, B, and C (14). There exist various eye involvement in Niemann-Pick disease.…”

Sphingomyelinases and Liver Diseases

“…An early diagnosis and appropriate handling are thus crucial to lower complication risks, improving quality of life and avoiding extreme procedures such as splenectomy [131][132][133]. Liver biopsy, the diffusion capacity measured by spirometry, the spleen volume and several plasma markers of lipid-laden cells, fibrosis or inflammation are among the biomarkers that are currently used to diagnose NPA and NPB to ensure an appropriate management of the disease [134,135]. Currently, an efficient treatment for NPD type A/B is lacking, and symptomatic therapy has been the only available option for these patients.…”