Quantification of lysosphingomyelin and lysosphingomyelin-509 for the screening of acid sphingomyelinase deficiency.

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients. In this study, we report the utility of the quantification of LysoSM and LysoSM509 in DBS of patients from Latin America with ASMD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). RESULTS: DBS samples from 14 ASMD patients were compared with 15 controls, and 44 general newborns. All patients had their diagnosis confirmed by the quantification of ASM and the measurement of the activity of chitotriosidase. All patients had significantly higher levels of lysoSM and lysoSM509 compared to controls and general newborns. CONCLUSIONS: The quantification of lysosphingolipids in DBS is a valuable tool for the diagnosis of ASMD patients and lysoSM can be useful in the differential diagnosis with NPC. This method is also valuable in the ASMD newborn screening process.

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

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a rare group of autosomal recessive disorders. This report provides the first detailed description of the periodontal condition and treatment response in a patient with chronic visceral ASMD. CASE DESCRIPTION: A 49-year-old white woman with ASMD showed elevated visible plaque index (VPI), gingival bleeding index (GBI), and bleeding on probing (BOP) at 100% of sites. Periodontal pocket depths (PPD) were mostly shallow to moderate (at 96% of sites), whereas the loss of clinical attachment (CAL) was moderate to severe (54% and 46% of sites, respectively, at 4-6 mm and ≥7 mm categories). Periapical radiographs revealed the presence of furcation involvement and intra-bony defects. The periodontal diagnosis was periodontitis stage IV, generalized, grade C. Ninety days after the end of the supra and subgingival control (e.g., cause-related therapy), marked reduction was observed for all periodontal indicators: VPI (-83%), GBI (-79%), BOP (-85%), elimination of sites PPD ≥7 mm, 27% increase in sites PPD 1-3 mm (from 64% to 91%), and gain of clinical attachment (gain of 11% CAL 1-3 mm and 25% CAL 4-6 mm; and a reduction of 36% CAL ≥7 mm). PRACTICAL IMPLICATIONS: Despite the severity of the initial periodontal condition, the patient with chronic visceral ASMD responded well to the non-surgical periodontal treatment.

Oral, dental, and craniofacial features in chronic acid sphingomyelinase deficiency.

The aim of this study was to evaluate the oral, dental, and craniofacial features of individuals affected by the chronic forms of acid sphingomyelinase deficiency (ASMD). This study comprised a sample of adult and pediatric patients (n = 8) with chronic ASMD. The individuals underwent oral examinations to evaluate the occurrence of caries, as well as full-mouth periodontal examinations, to assess the occurrence and severity of periodontal diseases. Panoramic and profile radiographs were obtained to analyze dental conditions and craniofacial parameters. Participants also answered questionnaires to identify systemic impairment, parafunctional habits, and bruxism. Dental anomalies of size, shape, and number were found, with agenesis and microdontia being the predominant findings. The average of caries experience was 11.75 (±8.1). Only one patient had periodontal health and all adult individuals had periodontitis at different stages and degrees. Bruxism was found in 87.5% of the sample. The convex profile and maxillary and mandibular retrusion were the most relevant findings in the cephalometric analysis. It is concluded that individuals with chronic ASMD, in addition to several systemic manifestations, present significant modifications in their oral health, from a greater occurrence of dental anomalies, caries, periodontal disease, in addition to skeletal changes.

Niemann-Pick disease A or B in four pediatric patients and SMPD1 mutation carrier frequency in the Mexican population.

INTRODUCTION AND OBJECTIVES: Niemann-Pick disease type A (NPD-A) and B (NPD-B) are lysosomal storage diseases with a birth prevalence of 0.4-0.6/100,000. They are caused by a deficiency in acid sphingomyelinase, an enzyme encoded by SMPD1. We analyzed the phenotype and genotype of four unrelated Mexican patients, one with NPD-A and three with NPD-B. PATIENTS AND METHODS: Four female patients between 1 and 7 years of age were diagnosed with NPD-A or NPD-B by hepatosplenomegaly, among other clinical characteristics, and by determining the level of acid sphingomyelinase enzymatic activity and sequencing of the SMPD1 gene. Additionally, a 775bp amplicon of SMPD1 (from 11:6393835_6394609, including exons 5 and 6) was analyzed by capillary sequencing in a control group of 50 unrelated healthy Mexican Mestizos. RESULTS: An infrequent variant (c.1343A>G p.Tyr448Cys) was observed in two patients. One is the first NPD-A homozygous patient reported with this variant and the other a compound heterozygous NPD-B patient with the c.1829_1831delGCC p.Arg610del variant. Another compound heterozygous patient had the c.1547A>G p.His516Arg variant (not previously described in affected individuals) along with the c.1805G>A p.Arg602His variant. A new c.1263+8C>T pathogenic variant was encountered in a homozygous state in a NPD-B patient. Among the healthy control individuals there was a heterozygous carrier for the c.1550A>T (rs142787001) pathogenic variant, but none with the known pathogenic variants in the 11:6393835_6394609 region of SMPD1. CONCLUSIONS: The present study provides further NPD-A or B phenotype-genotype correlations. We detected a heterozygous carrier with a pathogenic variant in 1/50 healthy Mexican mestizos.

Trypanosoma cruzi modulates gene expression of plasma membrane repair-related proteins.

Plasma membrane injury and repair is particularly prevalent in muscle cells. Here, we aimed to verify dysferlin, acid sphingomyelinase and transcriptional factor EB gene expression during Trypanosoma cruzi infection in vitro and in vivo. Our results showed that the parasite modulates gene expression of these proteins in a way dependent on the number of plasma membrane interacting parasites and in a rapamycin-sensitive manner.