Sterol profiles in plasma and erythrocyte membranes in patients with Smith-Lemli-Opitz syndrome: a six-year experience

2011 ◽  
Vol 49 (12) ◽  
Author(s):  
Gaetano Corso ◽  
Monica Gelzo ◽  
Rosalba Barone ◽  
Stefano Clericuzio ◽  
Pierluigi Pianese ◽  
...  
Keyword(s):  
Storage Time ◽  
Cholesterol Biosynthesis ◽  
Erythrocyte Membranes ◽  
Gas Chromatography Mass Spectrometry ◽  
Chondrodysplasia Punctata ◽  
Inborn Errors ◽  
Cholesterol Ratio ◽  
Negative Linear Correlation ◽  
Opitz Syndrome

AbstractThis study reports our experience over the last six years in the diagnosis of Smith-Lemli-Opitz syndrome and other inborn errors of cholesterol biosynthesis.Gas chromatography/mass spectrometry was used to obtain sterol profiles in plasma and erythrocyte membranes of suspected patients.Plasma sterol reference values calculated in unaffected subjects (n=276) were in agreement with those previously reported. Among patients investigated from 2005 to 2010, we report 16 patients affected by Smith-Lemli-Opitz syndrome, three of whom represent new cases and 13 of whom were follow-up patients. In this period we also identified a new case of chondrodysplasia punctata 2 X-linked. The estimated incidence obtained for Smith-Lemli-Opitz syndrome was 1:93 suspected patients (1.08%). We also studied the effect of storage on the dehydrocholesterols/cholesterol ratio in plasma and erythrocyte membranes of patients affected by Smith-Lemli-Opitz syndrome stored at –20°C for up to 22 and 20 months, respectively. A significant negative linear correlation between storage time and the dehydrocholesterols/cholesterol ratio was identified in both plasma and erythrocyte membranes. The decrease in the dehydrocholesterols/cholesterol ratio in erythrocyte membranes was at least two-fold higher than in plasma.The results of this study may be helpful for diagnosis and interpretation of data in patients with findings suggestive of a cholesterol biosynthesis defect.

Precholesterol Sterols Accumulate in Lipid Rafts of Patients with Smith-Lemli-Opitz Syndrome and X-Linked Dominant Chondrodysplasia Punctata

2008 ◽  
Vol 11 (2) ◽  
pp. 128-132 ◽  
Author(s):  
Dinesh Rakheja ◽  
Richard L. Boriack
Keyword(s):  
Lipid Rafts ◽  
Hedgehog Signaling ◽  
Cholesterol Biosynthesis ◽  
Membrane Lipid ◽  
Chondrodysplasia Punctata ◽  
Autopsy Material ◽  
Cholesterol Levels ◽  
Abnormal Accumulation ◽  
Hedgehog Proteins ◽  
Opitz Syndrome

Systemic fetal dysmorphogenesis in disorders of postsqualene cholesterol biosynthesis is thought to be caused by disruption of Hedgehog signaling. Because precholesterol sterols such as 7-dehydrocholesterol and lathosterol can replace cholesterol in the activation of Hedgehog proteins, it is currently believed that cholesterol deficiency-related Hedgehog signaling block occurs further downstream, probably at the level of Smoothened. Experimentally, such a block in Hedgehog signaling occurs at sterol levels of <40 μg/mg protein. Recently, we studied autopsy material from 2 infants with fatal cholesterol biosynthetic disorders (Smith-Lemli-Opitz syndrome and X-linked dominant chondrodysplasia punctata) in which the hepatic cholesterol levels were far greater. In this study, we demonstrate abnormal accumulation of sterol precursors of cholesterol in membrane lipid rafts (detergent resistance membranes) prepared from liver tissues of these 2 infants: 8-dehydrocholesterol and 7-dehydrocholesterol in lipid rafts of the infant with Smith-Lemli-Opitz syndrome and cholest-8(9)-ene-3β-ol in lipid rafts of the infant with X-linked dominant chondrodysplasia punctata. We suggest that such alterations in the lipid raft sterol environment may affect the biology of cells and the development of fetuses with cholesterol biosynthetic disorders.

scholarly journals Glomerular function in relation to fine airborne particulate matter in a representative population sample

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying-Mei Feng ◽  
Lutgarde Thijs ◽  
Zhen-Yu Zhang ◽  
Esmée M. Bijnens ◽  
Wen-Yi Yang ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Population Sample ◽  
Airborne Particulate Matter ◽  
Blood Stream ◽  
Renal Outcome ◽  
Cross Sectional ◽  
Cholesterol Ratio ◽  
Median Serum ◽  
Renal Responses

AbstractFrom 1990 until 2017, global air-pollution related mortality increased by 40%. Few studies addressed the renal responses to ultrafine particulate [≤ 2.5 µm (PM2.5)], including black carbon (BC), which penetrate into the blood stream. In a Flemish population study, glomerular filtration estimated from serum creatinine (eGFR) and the urinary albumin-to-creatinine ratio were measured in 2005–2009 in 820 participants (women, 50.7%; age, 51.1 years) with follow-up of 523 after 4.7 years (median). Serum creatinine, eGFR, chronic kidney disease (eGFR < 60 mL/min/1.73 m2) and microalbuminuria (> 3.5/> 2.5 mg per mmol creatinine in women/men) were correlated in individual participants via their residential address with PM2.5 [median 13.1 (range 0.3–2.9) μg/m3] and BC [1.1 (0.3–18) μg/m3], using mixed models accounting for address clusters. Cross-sectional and longitudinally, no renal outcome was associated with PM2.5 or BC in models adjusted for sex and baseline or time varying covariables, including age, blood pressure, heart rate, body mass index, plasma glucose, the total-to-HDL serum cholesterol ratio, alcohol intake, smoking, physical activity, socioeconomic class, and antihypertensive treatment. The subject-level geocorrelations of eGFR change with to BC and PM2.5 were 0.13 and 0.02, respectively (P ≥ 0.68). In conclusion, in a population with moderate exposure, renal function was unrelated to ultrafine particulate.

Characterization and outcome of 11 children with non-diabetic ketoacidosis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Elsayed Abdelkreem ◽  
Rofaida M. Magdy ◽  
Abdelrahim A. Sadek
Keyword(s):  
Diabetic Ketoacidosis ◽  
Case Series ◽  
Inborn Errors ◽  
Laboratory Features ◽  
Level 3 ◽  
Conscious Level ◽  
Neurodevelopmental Impairment ◽  
Salicylate Intoxication ◽  
Prompt Diagnosis

AbstractObjectivesTo study the clinical and laboratory features, management, and outcome of pediatric non-diabetic ketoacidosis (NDKA).MethodsBetween May 2018 and April 2020, we prospectively collected children under 18 years who presented with ketoacidosis, defined as ketosis (urinary ketones ≥++ and/or serum β-hydroxybutyrate level ≥3 mmol/L) and metabolic acidosis (pH <7.3 and HCO3− <15 mmol/L). Children with HbA1c level ≥6.5% at initial presentation and those meeting the diagnostic criteria for DM during follow-up were excluded. Data were collected on demographics, clinical and laboratory features, management, and outcome.ResultsEleven children with 19 episodes of NDKA were identified. The median age was 12 months (range from 5 months to 5 years). They manifested dehydration and disturbed conscious level (all cases), convulsions (n=6), hypoglycemia (n=6), hyperglycemia (n=2) and significant hyperammonemia (n=4). Most cases required intensive care management. Death or neurodevelopmental impairment occurred in six cases. Seven cases had inborn errors of metabolism (IEMs). Other cases were attributed to starvation, sepsis, and salicylate intoxication.ConclusionsThis is the largest case series of pediatric NDKA. Ketoacidosis, even with hyperglycemia, is not always secondary to diabetes mellitus. IEMs may constitute a significant portion of pediatric NDKA. Increased awareness of this unfamiliar condition is important for prompt diagnosis, timely management, and better outcome.

scholarly journals 7-Dehydrocholesterol down-regulates cholesterol biosynthesis in cultured Smith-Lemli-Opitz syndrome skin fibroblasts

1998 ◽  
Vol 39 (3) ◽  
pp. 647-657 ◽  
Author(s):  
Megumi Honda ◽  
G.S. Tint ◽  
Akira Honda ◽  
Lien B. Nguyen ◽  
Thomas S. Chen ◽  
...  
Keyword(s):  
Cholesterol Biosynthesis ◽  
Skin Fibroblasts ◽  
Opitz Syndrome

Fresh Osteochondral Allograft Transplantation: Is Graft Storage Time Associated With Clinical Outcomes and Graft Survivorship?

2017 ◽  
Vol 45 (10) ◽  
pp. 2260-2266 ◽  
Author(s):  
Kenneth J. Schmidt ◽  
Luís E. Tírico ◽  
Julie C. McCauley ◽  
William D. Bugbee
Keyword(s):  
Clinical Outcomes ◽  
Storage Time ◽  
Osteochondral Allograft ◽  
Prolonged Storage ◽  
Graft Size ◽  
Early Release ◽  
Fresh Osteochondral Allograft ◽  
Release Group ◽  
The Mean

Background: Regulatory concerns and the popularity of fresh osteochondral allograft (OCA) transplantation have led to a need for prolonged viable storage of osteochondral grafts. Tissue culture media allow a longer storage time but lead to chondrocyte death within the tissue. The long-term clinical consequence of prolonged storage is unknown. Hypothesis: Patients transplanted with OCAs with a shorter storage time would have lower failure rates and better clinical outcomes than those transplanted with OCAs with prolonged storage. Study Design: Cohort study; Level of evidence, 3. Methods: A matched-pair study was performed of 75 patients who received early release grafts (mean storage, 6.3 days [range, 1-14 days]) between 1997 and 2002, matched 1:1 by age, diagnosis, and graft size, with 75 patients who received late release grafts (mean storage time, 20.0 days [range, 16-28 days]) from 2002 to 2008. The mean age was 33.5 years, and the median graft size was 6.3 cm2. All patients had a minimum 2-year follow-up. Evaluations included pain, satisfaction, function, failures, and reoperations. Outcome measures included the modified Merle d’Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) form, and Knee Society function (KS-F) scale. Clinical failure was defined as revision OCA transplantation or conversion to arthroplasty. Results: Among patients with grafts remaining in situ, the mean follow-up was 11.9 years (range, 2.0-16.8 years) and 7.8 years (range, 2.3-11.1 years) for the early and late release groups, respectively. OCA failure occurred in 25.3% (19/75) of patients in the early release group and 12.0% (9/75) of patients in the late release group ( P = .036). The median time to failure was 3.5 years (range, 1.7-13.8 years) and 2.7 years (range, 0.3-11.1 years) for the early and late release groups, respectively. The 5-year survivorship of OCAs was 85% for the early release group and 90% for the late release group ( P = .321). No differences in postoperative pain and function were noted between the groups. Ninety-one percent of the early release group and 93% of the late release group reported satisfaction with OCA results. Conclusion: The transplantation of OCA tissue with prolonged storage is safe and effective for large osteochondral lesions of the knee and has similar clinical outcomes and satisfaction to the transplantation of early release grafts.

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

2021 ◽  
Vol 9 (2) ◽  
pp. 137-144
Author(s):  
Abdolreza Medghalchi ◽  
◽  
Afagh Hassanzadeh Rad ◽  
Setila Dalili ◽  
◽  
...  
Keyword(s):  
Inborn Errors Of Metabolism ◽  
Genetic Disorders ◽  
Single Gene ◽  
Scientific Information ◽  
Narrative Review ◽  
Inborn Errors ◽  
Relevant Evidence ◽  
Ocular Manifestations ◽  
Inherited Metabolic Disorders

Context: Inborn errors of metabolism or Inherited Metabolic Disorders (IMD) are a class of genetic disorders that occur because of single-gene defects. Evidence Acquisition: In this narrative review article, the authors searched Institute for Scientific Information (ISI), Web of Science, PubMed, and Google Scholar for the relevant evidence. Results: The ocular manifestations of IMDs can be distinguished in different diseases such as Albinism, Cystinosis, Homocystinuria, and Sulfite oxidize deficiency, Mannosidosis, Fucosidosis, Sialidosis, etc. Conclusions: Due to the direct toxic mechanisms of abnormal metabolites on eyes and regarding the effect of eye monitoring on the follow-up, management, and treatment, a detailed ophthalmological assessment is essential.

scholarly journals Urinary steroid profiling in diagnostic evaluation of an unusual adrenal mass

2019 ◽  
Vol 2019 ◽  
Author(s):  
N F Lenders ◽  
J R Greenfield
Keyword(s):  
Sensitivity And Specificity ◽  
Serum Biochemistry ◽  
Diagnostic Evaluation ◽  
Gas Chromatography Mass Spectrometry ◽  
List Type ◽  
Steroid Profiling ◽  
Rare Tumours ◽  
Adrenal Masses ◽  
Urinary Steroid

Summary Adrenal oncocytomas are rare tumours, with only approximately 160 cases reported in the literature. We report the use of urinary steroid profiling as part of their diagnostic evaluation and prognostication. A 45-year-old woman presented with clinical features of hyperandrogenism. Serum biochemistry confirmed androgen excess and computed tomography (CT) demonstrated a 3.2 cm adrenal tumour with density 39 HU pre-contrast. Urine steroid profiling showed elevated tetrahydro-11 deoxycortisol (THS), which is associated with adrenal malignancy. Laparoscopic adrenalectomy was performed, and histopathology diagnosed adrenal oncocytoma. Serum and urinary biochemistry resolved post-operatively and remained normal at 1-year follow-up. Learning points: Differential diagnosis of adrenal masses is challenging. Current techniques for differentiating between tumour types lack sensitivity and specificity. 24-h urinary steroid profiling is a useful tool for reflecting steroid output from adrenal glands. Gas chromatography-mass spectrometry (GC-MS) of urinary steroid metabolites has sensitivity and specificity of 90% for diagnosing adrenocortical carcinoma. Adrenal oncocytoma are rare tumours. Differentiating between benign and malignant types is difficult. Data guiding prognostication and management are sparse.

scholarly journals Non-cell autonomous inhibition of the Shh pathway due to impaired cholesterol biosynthesis requires Ptch1/2

2020 ◽  
Author(s):  
Carian Jägers ◽  
Henk Roelink
Keyword(s):  
Sonic Hedgehog ◽  
Birth Defects ◽  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Shh Signaling ◽  
Shh Pathway ◽  
Opitz Syndrome ◽  
Cholesterol Precursors ◽  
G Protein Coupled ◽  
Mutant Cells

AbstractBirth defects due to congenital errors in enzymes involved cholesterol synthesis like Smith-Lemli-Opitz syndrome (SLOS) and Lathosterolosis cause an accumulation of cholesterol precursors and a deficit in cholesterol. The phenotype of both SLOS and Lathosterolosis have similarities to syndromes associated with abnormal Sonic hedgehog (Shh) signaling, consistent with the notion that impaired cholesterol signaling can cause reduced Shh signaling. Two multipass membrane proteins play central roles in Shh signal transduction, the putative Resistance, Nodulation and Division (RND) antiporters Ptch1 and Ptch2, and the G-protein coupled receptor Smoothened (Smo). Sterols have been suggested as cargo for Ptch1, while Smo activity can affected both positively and negatively by steroidal molecules. We demonstrate that mESCs mutant for 7-dehydroxycholesterol reductase (7dhcr) or sterol-C5-desaturase (sc5d) reduce the Hh response in nearby wildtype cells when grown in mosaic organoids. This non-cell autonomous inhibitory activity of the mutant cells required the presence of both Ptch1 and Ptch2. These observations support a model in which late cholesterol precursors that accumulate in cells lacking 7DHCR are the cargo for Ptch1 and Ptch2 activity that mediates the non-cell autonomous inhibition of Smo.

Sign in / Sign up

Export Citation Format

Share Document