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JBI Evidence Synthesis Mar 2024This review aimed to synthesize the experiences of patients with metachromatic leukodystrophy, adrenoleukodystrophy, or Krabbe disease and those of their families.
OBJECTIVE
This review aimed to synthesize the experiences of patients with metachromatic leukodystrophy, adrenoleukodystrophy, or Krabbe disease and those of their families.
INTRODUCTION
Leukodystrophies are metabolic diseases caused by genetic mutations. There are multiple forms of the disease, varying in age of onset and symptoms. The progression of leukodystrophies worsens central nervous system symptoms and significantly affects the lives of patients and their families.
INCLUSION CRITERIA
Qualitative studies on the experiences of patients with leukodystrophies and their family members were included. These experiences included treatments such as enzyme replacement therapy and hematopoietic stem cell transplantation; effects of tracheostomy and gastrostomy; burdens on the family, coordinating care within the health care system, and family planning due to genetic disorders. This review considered studies in any setting.
METHODS
MEDLINE (Ovid), CINAHL Plus (EBSCOhost), APA PsycINFO (EBSCOhost), Scopus, and MedNar databases were searched on November 18, 2022. Study selection, critical appraisal, data extraction, and data synthesis were conducted in accordance with the JBI methodology for systematic reviews of qualitative evidence, and synthesized findings were evaluated according to the ConQual approach.
RESULTS
Eleven studies were eligible for synthesis, and 45 findings were extracted corresponding with participants' voices. Of these findings, 40 were unequivocal and 5 were credible. The diseases in the included studies were metachromatic leukodystrophy and adrenoleukodystrophy; no studies were identified for patients with Krabbe disease and their families. These findings were grouped into 11 categories and integrated into 3 synthesized findings, including i) providing care by family members and health care providers as physical symptoms progress, which relates to effects of the characteristics of progressive leukodystrophies; ii) building medical teamwork to provide appropriate support services, comprising categories related to the challenges experienced with the health care system for patients with leukodystrophy and their families; and iii) coordinating family functions to accept and cope with the disease, which included categories related to family psychological difficulties and role divisions within the family. According to the ConQual criteria, the second synthesized finding had a low confidence level, and the first and third synthesized findings had a very low confidence level.
CONCLUSIONS
The synthesized findings of this review provide evidence on the experiences of patients with metachromatic leukodystrophy or adrenoleukodystrophy and their families. These findings indicate that there are challenges in managing a patient's physical condition and coordinating the health care system and family functions.
REVIEW REGISTRATION
PROSPERO CRD42022318805.
PubMed: 38533650
DOI: 10.11124/JBIES-23-00303 -
Journal of Inherited Metabolic Disease May 2021Among boys with X-Linked adrenoleukodystrophy, a subset will develop childhood cerebral adrenoleukodystrophy (CCALD). CCALD is typically lethal without hematopoietic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Among boys with X-Linked adrenoleukodystrophy, a subset will develop childhood cerebral adrenoleukodystrophy (CCALD). CCALD is typically lethal without hematopoietic stem cell transplant before or soon after symptom onset. We sought to establish evidence-based guidelines detailing the neuroimaging surveillance of boys with neurologically asymptomatic adrenoleukodystrophy.
METHODS
To establish the most frequent age and diagnostic neuroimaging modality for CCALD, we completed a meta-analysis of relevant studies published between January 1, 1970 and September 10, 2019. We used the consensus development conference method to incorporate the resulting data into guidelines to inform the timing and techniques for neuroimaging surveillance. Final guideline agreement was defined as >80% consensus.
RESULTS
One hundred twenty-three studies met inclusion criteria yielding 1285 patients. The overall mean age of CCALD diagnosis is 7.91 years old. The median age of CCALD diagnosis calculated from individual patient data is 7.0 years old (IQR: 6.0-9.5, n = 349). Ninety percent of patients were diagnosed between 3 and 12. Conventional MRI was most frequently reported, comprised most often of T2-weighted and contrast-enhanced T1-weighted MRI. The expert panel achieved 95.7% consensus on the following surveillance parameters: (a) Obtain an MRI between 12 and 18 months old. (b) Obtain a second MRI 1 year after baseline. (c) Between 3 and 12 years old, obtain a contrast-enhanced MRI every 6 months. (d) After 12 years, obtain an annual MRI.
CONCLUSION
Boys with adrenoleukodystrophy identified early in life should be monitored with serial brain MRIs during the period of highest risk for conversion to CCALD.
Topics: Adrenoleukodystrophy; Child; Child, Preschool; Consensus Development Conferences as Topic; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Neonatal Screening
PubMed: 33373467
DOI: 10.1002/jimd.12356 -
The Journal of Clinical Endocrinology... Nov 2018Adrenoleukodystrophy (ALD) is a peroxisomal disorder associated with neurologic decompensation and adrenal insufficiency. Newborn screening for ALD has recently been...
CONTEXT
Adrenoleukodystrophy (ALD) is a peroxisomal disorder associated with neurologic decompensation and adrenal insufficiency. Newborn screening for ALD has recently been implemented in five states with plans to expand to all 50 states in the United States. Adrenal insufficiency ultimately develops in most males with ALD, but the earliest age of onset is not well established.
OBJECTIVE
These clinical recommendations are intended to address screening for adrenal insufficiency in boys identified to have ALD by newborn screen.
PARTICIPANTS
Seven members of the Pediatric Endocrine Society Drug and Therapeutics/Rare Diseases Committee, with clinical experience treating children with ALD and adrenal insufficiency, and a pediatric endocrinologist and laboratory director were selected to be on the working committee.
CONSENSUS PROCESS
The authors comprised the working group and performed systematic reviews of the published literature regarding adrenal insufficiency and ALD. The recommendations were reviewed and approved by the larger Pediatric Endocrine Society Drug and Therapeutics/Rare Diseases Committee and then by the Pediatric Endocrine Society Board of Directors.
CONCLUSIONS
There is limited literature evidence regarding monitoring of evolving adrenal insufficiency in male infants and children with ALD. The recommendations suggest initiating assessment of adrenal function at diagnosis with ALD and regular monitoring to identify boys with adrenal insufficiency in a timely manner and prevent life-threatening adrenal crisis. These recommendations are intended to serve as an initial guide, with the understanding that additional experience will inform future guidelines.
Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adrenoleukodystrophy; Aldosterone; Diagnostic Techniques, Endocrine; Endocrinology; Humans; Hydrocortisone; Infant, Newborn; Male; Neonatal Screening; North America; Reference Values; Societies, Medical
PubMed: 30289543
DOI: 10.1210/jc.2018-00920 -
European Journal of Internal Medicine Jan 2014Gene therapy, replacing a defective gene by a functional copy, has been in development for more than 40years. Initial efforts involved engineering viral vectors to... (Review)
Review
BACKGROUND
Gene therapy, replacing a defective gene by a functional copy, has been in development for more than 40years. Initial efforts involved engineering viral vectors to deliver genes to the appropriate cells. Early successes in severe combined immunodeficiency (SCID) were later derailed by safety issues including host reaction to the vector and gene insertion near promoters that favored secondary leukemia.
METHODS
Systematic review of the literature using PubMed.gov with key word gene therapy from 1972 to March 2013. Google search with key word gene therapy.
RESULTS
Despite early setbacks, progresses for monogenic diseases continued unabated. Patients with SCIDs have been cured and the first gene therapy has been approved for lipoprotein lipase deficiency. Many clinical research studies are ongoing as part of systematic clinical development program with a view to have more gene therapies approved.
CONCLUSION
Our review highlights progresses and questions that remain to be answered to make gene therapy an integral part of our therapeutic arsenal.
Topics: Adrenoleukodystrophy; Dependovirus; Genetic Therapy; Genetic Vectors; Hemophilia B; Humans; Hyperlipoproteinemia Type I; Lentivirus; Retroviridae; Severe Combined Immunodeficiency
PubMed: 24129166
DOI: 10.1016/j.ejim.2013.09.009 -
Genetic Counseling (Geneva, Switzerland) 2005The objective of this article is to review the attitudes of the different stakeholders (minors, healthcare professionals, parents and relatives of affected individuals)... (Meta-Analysis)
Meta-Analysis Review
The objective of this article is to review the attitudes of the different stakeholders (minors, healthcare professionals, parents and relatives of affected individuals) towards carrier testing in minors. The databases Pubmed, Google Scholar, Psychinfo, Biological Abstracts, Francis, Anthropological Index online, Web of Science, and Sociological Abstracts were searched using key words for the period 1990-2004. Studies were included if they were published in a peer reviewed journal in English and described the attitudes of minors, parents or healthcare professionals towards carrier testing in minors in a family context. The results were presented in a summary form. In total 20 relevant studies were retrieved (2 studies reported the attitudes of two stakeholders). Only one study reported the attitudes of adolescents, two studies reported the attitudes of adults who had undergone carrier testing in childhood. In total six studies have been retrieved discussing the parental attitudes towards carrier testing in their children. Over all studies, most parents showed interest in detecting their children's carrier status and responded they wanted their child tested before the age of majority: some parents even before 12 years. Eight studies were retrieved that reported the attitudes of relatives of affected individuals. Most were in favor of carrier testing before 18 years. The studies retrieved suggest that most parents are interested in the carrier status of their children and want their children to be tested before they reach legal majority (and some even in childhood). This can lead to tensions between parents and healthcare professionals regarding carrier testing in minors. Guidelines of healthcare professionals advise to defer carrier testing on the grounds that children should be able to decide for themselves later in life to request a carrier test or not.
Topics: Adolescent; Adrenoleukodystrophy; Attitude; Attitude of Health Personnel; Child; Cystic Fibrosis; Fragile X Syndrome; Genetic Carrier Screening; Glucosephosphate Dehydrogenase Deficiency; Hemophilia A; Humans; Muscular Dystrophy, Duchenne; Parents; Predictive Value of Tests; beta-Thalassemia
PubMed: 16440876
DOI: No ID Found