Loes Score: Clinical and Radiological Profile of 22 Patients of X-Linked Adrenoleukodystrophy: Case Series from a Single Center.
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SUBMITTER: Kumar S
PROVIDER: S-EPMC8448211 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe present study was aimed at evaluating the correlation between diffusion tensor imaging parameters and Loes score as well as whether those parameters could indicate early structural alterations.Materials and methodsDiffusion tensor imaging measurements were obtained in 30 studies of 14 patients with X-linked adrenoleukodystrophy and were correlated with Loes scores. A control group including 28 male patients was created to establish agematched diffusion tensor imaging measurements. Inter- and intraobserver statistical analyses were undertaken.ResultsDiffusion tensor imaging measurements presented strong Pearson correlation coefficients (r) of -0.86, 0.89, 0.89 and 0.84 for fractional anisotropy and mean, radial and axial diffusivities (p < 0.01). Analysis of changes in diffusion tensor measurements at early stage of the disease indicates that mean and radial diffusivities might be useful to predict the disease progression.ConclusionMeasurements of diffusion tensor parameters can be used as an adjunct to the Loes score, aiding in the monitoring of the disease and alerting for possible Loes score progression in the range of interest for therapeutic decisions.
| S-EPMC4341377 | biostudies-literature
Project description:Rationale & Objective:The world is facing a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although kidney transplant recipients are at increased risk for viral infections, the impact of their chronic immunosuppressed status on the risk for acquiring coronavirus disease 2019 (COVID-19) and disease severity is unknown. Study Design:All cases of COVID-19 infection in our cohort of kidney transplant recipients were prospectively monitored. Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients. Setting & Participants:22 COVID-19 infections were diagnosed in our cohort of 1,200 kidney transplant recipients. Results:Most common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n = 3), moderate (n = 8), extensive (n = 1), severe (n = 2), and critical (n = 1) involvement. Immunosuppression reduction was initiated in all patients. Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died. Limitations:Small sample size and short follow-up. Conclusions:The clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.
| S-EPMC7295531 | biostudies-literature
Project description:BackgroundRenal pelvic hemangioma (RPH) is often misdiagnosed as renal pelvis cancer (RPC) due to its similarity in presentation, and there are few reports on the imaging findings of RPH. This study is aimed at improving the understanding of imaging findings specific for RPH by a retrospective analysis of the imaging findings of RPH.MethodsRPH cases confirmed by pathology and with high-quality images were collected in the analysis. Nine cases of RPH were enrolled, of which 6 cases underwent ultrasound (US); 7 cases underwent computed tomography (CT), including 6 cases with an enhanced scan; and 2 cases underwent magnetic resonance imaging (MRI), including 1 case with an enhanced scan. All images of cases were analyzed and sorted independently by two senior attending radiologist blinded to the pathological results, according to the imaging indicators, such as the density and intensity on CT and MRI respectively. When the opinions between radiologists were inconsistent, images were re-evaluated together until a consensus was reached.ResultsNine cases of RPH were collected from 5 males and 4 females, aged 16-70 years old, with a median age of 41 years. Five cases were located in the left kidney and 4 cases were located in the right kidney. The clinical symptoms mostly presented with hematuria. Nine cases demonstrated solitary masses, with 4 cases with blurred margins and 5 cases with well-defined margins. The size of the mass was about 1.5-8.0 cm, and the median size was 2.5 cm. The US showed mostly hypoechoic masses and color Doppler flow imaging (CDFI) showed minimal to no blood flow signal. Unenhanced CT scans showed mostly hypodensity and mostly mild continuous enhancement on an enhanced scan. The intensity of lesions was commonly heterogeneous on MRI due to hemorrhage and necrosis. One case showed mild continuous enhancement on an enhanced MRI scan.ConclusionsThe imaging findings of RPH commonly present as a focal lesion with blurred or well-defined margins, mild and continuous enhancement, and no cachexia of the clinical symptoms. RPH should be differentiated from malignant tumors of the renal pelvis for treatment.
| S-EPMC8575578 | biostudies-literature
Project description:X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene and is characterized by impaired beta-oxidation of very-long-chain fatty acids (VLCFA) and subsequent VLCFA accumulation in tissues. In adulthood X-ALD most commonly manifests as a gradually progressive myelopathy, (adrenomyeloneuropathy; AMN) without any curative or disease modifying treatments. We recently showed that bezafibrate (BF), a drug used for the treatment of hyperlipidaemia, reduces VLCFA accumulation in X-ALD fibroblasts by inhibiting ELOVL1, an enzyme involved in the VLCFA synthesis. We therefore designed a proof-of-principal clinical trial to determine whether BF reduces VLCFA levels in plasma and lymphocytes of X-ALD patients. Ten males with AMN were treated with BF for 12 weeks at a dose of 400 mg daily, followed by 12 weeks of 800 mg daily. Every 4 weeks patients were evaluated for side effects and blood samples were taken for analysis. Adherence was good as indicated by a clear reduction in triglycerides. There was no reduction in VLCFA in either plasma or lymphocytes. Plasma levels of BF did not exceed 25 µmol/L. We concluded that BF, at least in the dose given, is unable to lower VLCFA levels in plasma or lymphocytes in X-ALD patients. It is unclear whether this is due to the low levels of BF reached in plasma. Our future work is aimed at the identification of highly-specific inhibitors of ELOVL1 that act at much lower concentrations than BF and are well tolerated. BF appears to have no therapeutic utility in X-ALD.ClinicalTrials.gov NCT01165060.
| S-EPMC3401223 | biostudies-literature
Project description:Currently the molecular basis for the clinical heterogeneity of X-linked adrenoleukodystrophy (X-ALD) is poorly understood. The genetic bases for all different phenotypic variants of X-ALD are mutations in the gene encoding the peroxisomal ATP-binding cassette (ABC) transporter, ABCD1 (formerly adrenoleukodystrophy protein, ALDP). ABCD1 transports CoA-activated very long-chain fatty acids from the cytosol into the peroxisome for degradation. The phenotypic variability is remarkable ranging from cerebral inflammatory demyelination of childhood onset, leading to death within a few years, to adults remaining pre-symptomatic through more than five decades. There is no general genotype-phenotype correlation in X-ALD. The default manifestation of mutations in ABCD1 is adrenomyeloneuropathy, a slowly progressive dying-back axonopathy affecting both ascending and descending spinal cord tracts as well as in some cases, a peripheral neuropathy. In about 60% of male X-ALD patients, either in childhood (35-40%) or in adulthood (20%), an initial, clinically silent, myelin destabilization results in conversion to a devastating, rapidly progressive form of cerebral inflammatory demyelination. Here, ABCD1 remains a susceptibility gene, necessary but not sufficient for inflammatory demyelination to occur. Although the accumulation of very long-chain fatty acids appears to be essential for the pathomechanism of all phenotypes, the molecular mechanisms underlying these phenotypes are fundamentally different. Cell autonomous processes such as oxidative stress and energy shortage in axons as well as non-cell autonomous processes involving axon-glial interactions seem pertinent to the dying-back axonopathy. Various dynamic mechanisms may underlie the initiation of inflammation, the altered immune reactivity, the propagation of inflammation, as well as the mechanisms leading to the arrest of inflammation after hematopoietic stem cell transplantation. An improved understanding of the molecular mechanisms involved in these events is required for the development of urgently needed therapeutics.
| S-EPMC3988840 | biostudies-literature
Project description:IntroductionRadiological evaluation of suspected COVID-19 patients is required for early detection of thoracic involvement, particularly in emergency units, while waiting for definitive diagnosis by real-time reverse transcription polymerase chain reaction (RT-PCR). Here, we report a case series of CXR findings in Indonesian patients with COVID-19 in our institution.Presentation of casesWe included 7 patients with COVID-19 confirmed by RT-PCR, including 4 females and 3 males, with ages ranging from 36 to 71 years. All patients showed abnormal findings on CXR when admitted to the hospital, except one, composed of ground glass opacity (GGO) (n = 1), consolidation (n = 3), and both (n = 2). Both and one side of the lung were affected in three and three (left side = 2; right side = 1) patients, respectively. Pneumonia degrees of mild, moderate and severe were observed in three, one, and two patients, respectively. All patients eventually recovered.DiscussionCXR is the most common radiological examination for patients with respiratory disorders, including COVID-19, and it is readily available in almost all health care facilities. The imaging manifestation of COVID-19 is similar to viral pneumonia but also has its own characteristics, including GGO, consolidation, multiple plaque shadows, and interstitial changes that are mostly seen in peripherals and subpleural areas, as well as shadow infiltration in both lungs.ConclusionCXR showed various abnormality findings in patients with COVID-19, including the type, location, and degree of pneumonia. Moreover, CXR is considered more effective and useful for initial screening and follow-up of the progress of patients with COVID-19.
| S-EPMC7826043 | biostudies-literature
Project description:X-linked adrenoleukodystrophy may present with a deceptively mild phenotype, even in adult males. Tight collaboration between clinicians, geneticists, biochemists, and other specialists is increasingly required for clarification of diagnosis in cases with atypical presentation.
| S-EPMC4736514 | biostudies-other
Project description:BackgroundSilvery Hair Syndromes (SHS), an autosomal recessive inherited disorder, includes Chediak-Higashi syndrome (CHS), Griscelli syndrome (GS), Hermansky-Pudlak syndrome (HPS), and Elejalde syndrome. Associated immunological and neurological defects and predilection for hemophagocytic lymphohistiocytosis (HLH) makes them a distinctive entity in pediatric practice. Thorough clinical examination, bedside investigations such as peripheral blood smear (PBS) and hair microscopy, and bone marrow (BM) examination are inexpensive and reliable diagnostic tools.MethodsWe report 12 cases with SHS (CHS, n = 06; GS, n = 04; HPS, n = 02).Results8 out of 12 SHS children (CHS-05, GS-03) presented with HLH. Out of 5 cases of CHS with HLH, 2 died, 3rd is stable post-chemotherapy; 4th completed chemotherapy, underwent matched related hematopoietic stem cell transplant (HSCT), and is stable 8 months off treatment. The 5th child completed chemotherapy and is in process of transplant. One CHS child without HLH is thriving without any treatment. Of the 4 GS cases, 3 presented with HLH and received chemotherapy (HLH 2004 protocol). One lost follow-up after initial remission; another had recurrence 7 months off treatment and discontinued further treatment. The third child had recurrence 1.5 years after initial chemotherapy; HLH 2004 protocol was restarted followed by HSCT from matched sibling donor; is currently well, 2.5 years post-transplant. One child with GS had neurological features with no evidence of HLH and did not take treatment. Of 2 children with HPS, one presented with severe sepsis and the other with neurological problems. They were managed symptomatically.ConclusionIn SHS with HLH, chemotherapy followed by allogeneic hematopoietic stem cell transplantation is a promising curative option.
| S-EPMC9455113 | biostudies-literature
Project description:RationaleX-linked adrenoleukodystrophy (X-ALD) is a rare disorder caused by mutations in the ABCD1 gene, coding for peroxisomal membrane transporter adrenoleukodystrophy (ALD) protein. The disease is characterized by accumulation of very long chain fatty acids (VLCFAs) in tissues. Adult adrenomyeloneuropathy (AMN) and the cerebral inflammatory form of ALD are the main phenotypes presenting various symptoms.Patient concernsWe report a case of 37-year-old patient with diagnosis of X-ALD, confirmed based on elevated VLCFA concentrations and genetic testing of ABCD1 gene. The complete clinical picture in the patient indicates AMN phenotype with cerebral involvement.DiagnosesThe reduced synthesis of unconjugated cholic and chenodeoxycholic acids, and the reduction to 28% to 29% of peroxisomal beta-oxidation of behenic acid and normal peroxisomal metabolism of pristanic and palmitic acid were observed in the X-ALD patient. Sanger sequencing of major genes involved in primary bile acid (BA) synthesis failed to identify pathogenic mutations of the investigated set of genes.InterventionsPlasma concentrations of BAs, VLCFAs, and beta-oxidation of C22:0, C16:0, and pristanic acid were studied in primary skin fibroblasts of the patient. In addition, we performed sequencing of the ABCD1, ABCD3, CYP7A1, CYP7B1, CYP27A1, HSD3B7, AKR1D1, and SLC27A5 genes in the X-ALD family.OutcomesIn the Polish family affected with AMN a dysregulation of the primary BA synthesis pathway was found.LessonsWe have demonstrated the coincidence of the adult form of X-ALD with abnormalities in BA synthesis. We suggest that decreased synthesis of BAs may be an additional dysfunction as a consequence of the ABCD1 c.659T>C, p.(Leu220Pro) mutation and may be further evidence that disturbed cholesterol metabolism is important in the pathology of ALD.
| S-EPMC6310492 | biostudies-literature
Project description:X-adrenoleukodystrophy (X-ALD) is a metabolic, peroxisomal disease affecting the nervous system, adrenal cortex and testis resulting from inactivating mutations in ABCD1 gene which encodes a peroxisomal membrane half-adenosine triphosphate (ATP)-binding cassette transporter, ABCD1 (or ALDP), whose defect is associated with impaired peroxisomal beta-oxidation and accumulation of saturated very long-chain fatty acids (VLCFA) in tissues and body fluids. Several phenotypes are recognized in male patients including cerebral ALD in childhood, adolescence or adulthood, adrenomyeloneuropathy (AMN), Addison's disease and, eventually, gonadal insufficiency. Female carriers might present with mild to severe myeloneuropathy that resembles AMN. There is a lack of phenotype-genotype correlations, as the same ABCD1 gene mutation may be associated with different phenotypes in the same family, suggesting that genetic, epigenetic, environmental and stochastic factors are probably contributory to the development and course of the disease. Degenerative changes, like those seen in pure AMN without cerebral demyelination, are characterized by loss of axons and secondary myelin in the long tracts of the spinal cord, possibly related to the impaired lipid metabolism of VLCFAs and the associated alterations (ie, oxidative damage). Similar lesions are encountered following inactivation of ABCD1 in mice (ABCD1(-)). A different and more aggressive phenotype is secondary to cerebral demyelination, very often accompanied by inflammatory changes in the white matter of the brain and associated with activation of T lymphocytes, CD1 presentation and increased levels of cytokines, gamma-interferon, interleukin (IL)-1alpha, IL-2 and IL-6, Granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha, chemokines and chemokine receptors.
| S-EPMC8094714 | biostudies-literature