Effectiveness of targeted therapy for kidney damage with tuberous sclerosis in a child (clinical case)

2021 ◽  
Vol 25 (4) ◽  
pp. 90-94
Author(s):  
S. L. Morozov ◽  
O. R. Piruzieva ◽  
V. V. Dlin
Keyword(s):  
Chronic Kidney Disease ◽  
Targeted Therapy ◽  
Tuberous Sclerosis ◽  
Clinical Case ◽  
Autosomal Dominant ◽  
Mtor Inhibitors ◽  
Kidney Damage ◽  
Early Age ◽  
Risk Of Bleeding ◽  
Genetically Determined

Tuberous sclerosis is a polysystemic, genetically determined, autosomal dominant orphan disease that affects approximately 1 in 10,000 people worldwide. Kidney damage in tuberous sclerosis is the leading cause of death due to serious complications, the most common of which is angiomyolipoma bleeding. A feature of renal angiomyolipomas is that they begin to progress and increase in volume from an early age, leading to the progression of chronic kidney disease, while angiomyolipomas more than 30 mm in diameter are at risk of bleeding. Currently, pharmacotherapy of tuberous sclerosis with mTOR inhibitors is the most effective worldwide. In this article, a clinical case of targeted therapy of tuberous sclerosis is presented, the effectiveness is demonstrated, and the features of the course of tuberous sclerosis are also given on a specific example.

Acute intermittent porphyria: familial disease cases (clinical observation)

2021 ◽  
pp. 28-39
Author(s):  
Nadezhda Viktorovna Kurkina ◽  
Vsevolod Vladimirovich Skvortsov ◽  
Ella Ivanovna Polozova ◽  
Valeriya Aleksandrovna Vyshinskaya
Keyword(s):  
Nervous System ◽  
Targeted Therapy ◽  
Clinical Response ◽  
Clinical Case ◽  
Clinical Observation ◽  
Autosomal Dominant ◽  
Acute Intermittent Porphyria ◽  
Autosomal Dominant Disorder ◽  
Mental Symptoms ◽  
Excessive Accumulation

Acute intermittent porphyria is a rare autosomal dominant disorder characterized by excessive accumulation and excretion of porphyrins and their precursors, repeated attacks of neurological and mental symptoms. Due to the rarity of this pathology and the atypical course in the onset, certain difficulties often arise during the initial diagnosis. The main pathogenetic drug is gemin (Normosang), which allows obtaining a stable clinical response and preventing the development of severe changes in the nervous system. This article presents an analysis of a clinical case of acute intermittent porphyria among blood relatives and discusses the effectiveness of targeted therapy.

scholarly journals Tuberous sclerosis syndrome: a typical case of a rare disease

2018 ◽  
Vol 94 (4) ◽  
pp. 49-54
Author(s):  
V. A. Okhlopkov ◽  
E. A. Zykova ◽  
O. V. Pravdina
Keyword(s):  
Differential Diagnosis ◽  
Rare Disease ◽  
Tuberous Sclerosis ◽  
Clinical Picture ◽  
Clinical Case ◽  
Autosomal Dominant ◽  
Hereditary Disease ◽  
Typical Case ◽  
Dominant Type ◽  
Autosomal Dominant Type

The article is devoted to a rare hereditary disease from the group of phak omatoses with an autosomal dominant type of inheritance — Pringle — Burnevill disease. The questions of the prevalence of the disease, the variability of the clinical picture, the timeliness of the clinical diagnosis are considered. Particular attention is paid to skin manifestations and their differential diagnosis. A clinical case of this disease is described.

Clinical Case Studies in Renal Transplantation

2013 ◽  
Vol 12 (2) ◽  
pp. 75-75
Keyword(s):  
Risk Assessment ◽  
Chronic Kidney Disease ◽  
Pulmonary Hypertension ◽  
Renal Transplantation ◽  
Kidney Disease ◽  
Case Studies ◽  
Clinical Case ◽  
Hemodynamic Evaluation ◽  
Clinical Case Studies

The case studies below are referred to in the articles “Pulmonary Hypertension in Patients with Chronic Kidney Disease: Noninvasive Strategies for Patient Phenotyping and Risk Assessment” by Amresh Raina, MD, and “Hemodynamic Evaluation of Pulmonary Hypertension in Chronic Kidney Disease” by Ryan Tedford, MD, and Paul Forfia, MD, on the following pages.

scholarly journals Association of leukocyte telomere length with chronic kidney disease in East Asians with type 2 diabetes: A Mendelian randomization study

2021 ◽  
Author(s):  
Resham L Gurung ◽  
Rajkumar Dorajoo ◽  
Yiamunaa M ◽  
Ling Wang ◽  
Sylvia Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Telomere Length ◽  
Mendelian Randomization ◽  
Random Effect ◽  
Leukocyte Telomere Length ◽  
Increased Risk ◽  
Genetically Determined

Abstract Background Chronic kidney disease (CKD) is common among type 2 diabetes (T2D) and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length is associated with CKD in patients with T2D. We previously reported single nucleotide polymorphisms (SNPs) associated with leukocyte telomere length in Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using Mendelian randomization (MR) approach. Methods The cross-sectional association of 16 leukocyte telomere length SNPs with CKD, defined as an estimated glomerular filtration rate of less than 60 ml/min/1.73m2 was assessed among 4,768 (1,628 cases, 3,140 controls) participants in the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes and Diabetic Nephropathy cohorts. MR analysis was performed using the random-effect inverse-variance weighted (IVW) method, the weighted median, MR-Egger and Radial MR adjusted for age and sex-stratified by cohorts and ethnicity (Chinese and Malays), then meta-analysed. Results Genetically determined shorter leukocyte telomere length was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio = 1.51 [95% confidence interval, 1.12 - 2.12; P = 0.007; Phet= 0.547]). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (β  =  0.010, P = 0.751). Conclusions Our findings suggest that genetically determined leukocyte telomere length is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.

scholarly journals Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex in children, adolescents, and caregivers: a multicenter cohort study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Janina Grau ◽  
Johann Philipp Zöllner ◽  
Susanne Schubert-Bast ◽  
Gerhard Kurlemann ◽  
Christoph Hertzberg ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Direct Cost ◽  
Nursing Care ◽  
Tuberous Sclerosis Complex ◽  
Indirect Costs ◽  
Mtor Inhibitors ◽  
Direct Costs ◽  
Driving Factors ◽  
Care Level ◽  
Organ Manifestations

Abstract Background Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients. Methods A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany. Results The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7–21.8 years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088–5863, median EUR 2062] per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027–1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221–3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193–586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs. Conclusions This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting. Trial registration: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

scholarly journals The effect of sirolimus on angiomyolipoma is determined by decrease of fat-poor compartments and includes striking reduction of vascular structures

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elieser Hitoshi Watanabe ◽  
Fernando Morbeck Almeida Coelho ◽  
Hilton Leão Filho ◽  
Bruno Eduardo Pedroso Balbo ◽  
Precil Diego Miranda de Menezes Neves ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Blood Vessels ◽  
Tuberous Sclerosis Complex ◽  
Hounsfield Unit ◽  
Mtor Inhibitors ◽  
Volume Reduction ◽  
Tumor Reduction ◽  
Vascular Structures ◽  
Remarkable Reduction

AbstractRenal angiomyolipomas hemorrhage is associated with their size and vascular constitution. The effects of sirolimus on different components of angiomyolipomas was analyzed in patients with tuberous sclerosis complex, sporadic lymphangioleiomyomatosis and multiple sporadic angiomyolipomas. Thirty angiomyolipomas from 14 patients treated with sirolimus were retrospectively evaluated. A Hounsfield-unit threshold was used to classify angiomyolipomas in fat-rich, fat-poor and intermediate-fat tumors, and to categorize tumor compartments in fat rich, fat poor, intermediate fat and highly vascularized. Diameter variations were measured to assess the effects on aneurysmatic/ectatic vascular formations. Volume reduction following treatment with sirolimus was higher in fat-poor than fat-rich angiomyolipomas. Tumor reduction was mainly determined by decrease of the fat-poor and highly-vascularized compartments while the volume of the fat-rich compartment increased. Broad liposubstitution was observed in some tumors. A median reduction of 100% (75 to 100) in the diameter of aneurysmatic/ectatic vascular structures was observed. Our study showed that sirolimus reduces the size of angiomyolipomas by decreasing primarily their highly-vascularized and fat-poor compartments. This effect is associated with a remarkable reduction of tumoral aneurysms/ectatic vessels, revealing the likely mechanism responsible for the risk-decreasing effect of mTOR inhibitors on angiomyolipoma bleeding. These findings support the role of mTOR in the development of angiomyolipoma blood vessels.

scholarly journals A novel TSC1 variant associated with tuberous sclerosis and sacrococcygeal teratoma

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Saba Ahmad ◽  
Luis Manon ◽  
Gifty Bhat ◽  
Jerry Machado ◽  
Alice Zalan ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cellular Differentiation ◽  
Autosomal Dominant ◽  
De Novo ◽  
Autosomal Dominant Disease ◽  
Sacrococcygeal Teratoma ◽  
Dominant Disease ◽  
The Brain

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disease associated with tumors and malformed tissues in the brain and other vital organs. We report a novel de novo frameshift variant of the TSC1 gene (c.434dup;p. Ser146Valfs*8) in a child with TSC who initially presented with a sacral teratoma. This previously unreported association between TSC and teratoma has broad implications for the pathophysiology of embryonic tumors and mechanisms underlying cellular differentiation.

scholarly journals Two Cases of Tuberous Sclerosis With Multiple Rhabdomyoma Succumbing to Sudden Cardiac Death

2021 ◽  
pp. 263246362110124
Author(s):  
Manjappa Mahadevappa ◽  
Vikram Patil ◽  
K.S. Poornima ◽  
Sowmya Velamala ◽  
B.V. Guruprasad
Keyword(s):  
Sudden Cardiac Death ◽  
Tuberous Sclerosis ◽  
Cardiac Arrhythmias ◽  
Cardiac Death ◽  
Cardiac Involvement ◽  
Autosomal Dominant ◽  
Specific Treatment ◽  
Organ Systems ◽  
Dominant Condition ◽  
Variable Penetrance

Tuberous sclerosis complex is an autosomal dominant condition with variable penetrance. It is characterized by tuberose deposits in various organ systems. Although clinical features predominate neurocutaneous manifestations, cardiac, kidney, and lung involvement are common. Cardiac involvement is marked by the presence of multiple rhabdomyomas and in some cases arrhythmias. In the absence of symptoms, rhabdomyomas require no specific treatment. However, cardiac arrhythmias are unpredictable and may be the cause of sudden cardiac death in some cases. Although treatment is mainly symptomatic, drugs like rapamycin have shown promise in the regression of astrocytomas and angiofibromas. Here, we are reporting two cases of tuberous sclerosis of which one succumbed to arrhythmias and the other to possible sudden cardiac death.

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