High prevalence of primary adrenal insufficiency in Zellweger spectrum disorders

Berendse, Kevin; Engelen, Marc; Linthorst, Gabor E.; Trotsenburg, A S Paul van; Poll-Thé, Bwee Tien

doi:10.1186/s13023-014-0133-5

Cited by 37 publications

(29 citation statements)

References 11 publications

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“…A recent study reported a high prevalence of primary adrenal insufficiency in a population of 29 PBD-ZSD patients [76]. It is recommended that after one year of age, yearly (or more frequent) adrenal monitoring with adrenocorticotropic hormone (ACTH) and morning cortisol be performed.…”

Section: Management and Treatment Guidelinesmentioning

confidence: 99%

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines

Braverman

Raymond

Rizzo

et al. 2016

Molecular Genetics and Metabolism

208

207

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Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care.

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Section: Management and Treatment Guidelinesmentioning

confidence: 99%

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines

Braverman

Raymond

Rizzo

et al. 2016

Molecular Genetics and Metabolism

208

207

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“…This chronic accumulation of cholesterol with saturated VLCFA is believed to result in apoptosis and ultimately atrophy of the adrenal cortex, with loss of cortisol production 41 . Notably, adrenal insufficiency has also been reported in patients with a Zellweger spectrum disorder 42,43 , who also accumulate VLCFA in their adrenal glands. This observation, therefore, lends further support to the notion that VLCFA accumulation is important in the pathophysiology of adrenal insufficiency.…”

mentioning

confidence: 93%

Adrenoleukodystrophy – neuroendocrine pathogenesis and redefinition of natural history

et al. 2016

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X-Linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with a highly complex clinical presentation. ALD is caused by mutations in the ABCD1 gene, which leads to the accumulation of very long-chain fatty acids in plasma and tissues. Virtually all men with ALD develop adrenal insufficiency and myelopathy. Approximately 60% of men develop progressive cerebral white matter lesions (known as cerebral ALD). However, one cannot identify these individuals until the early changes are seen using brain imaging. Women with ALD also develop myelopathy, but generally at a later age than men and adrenal insufficiency or cerebral ALD are very rare. Owing to the multisystem symptomatology of the disease, patients can be assessed by the paediatrician, general practitioner, endocrinologist or a neurologist. This Review describes current knowledge on the clinical presentation, diagnosis and treatment of ALD, and highlights gaps in our knowledge of the natural history of the disease owing to an absence of large-scale prospective cohort studies. Such studies are necessary for the identification of new prognostic biomarkers to improve care for patients with ALD, which is particularly relevant now that newborn screening for ALD is being introduced.

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“…We follow a phenotypically and genetically heterogeneous cohort of ZSD patients at the Academic Medical Centre in Amsterdam . All patients are regularly examined including physical exams and laboratory check‐ups.…”

Section: Methodsmentioning

confidence: 99%

“…We follow a phenotypically and genetically heterogeneous cohort of ZSD patients at the Academic Medical Centre in Amsterdam. [6][7][8] All patients are regularly examined including physical exams and laboratory check-ups. Typically, examinations also include abdominal ultrasounds and for almost all patients results of a magnetic resonance imaging (MRI) of the brain is available.…”

Section: Patientsmentioning

confidence: 99%

Development and validation of a severity scoring system for Zellweger spectrum disorders

et al. 2017

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The lack of a validated severity scoring system for individuals with Zellweger spectrum disorders (ZSD) hampers optimal patient care and reliable research. Here, we describe the development of such severity score and its validation in a large, well-characterized cohort of ZSD individuals. We developed a severity scoring system based on the 14 organs that typically can be affected in ZSD. A standardized and validated method was used to classify additional care needs in individuals with neurodevelopmental disabilities (Capacity Profile [CAP]). Thirty ZSD patients of varying ages were scored by the severity score and the CAP. The median score was 9 (range 6-19) with a median scoring age of 16.0 years (range 2-36 years). The ZSD severity score was significantly correlated with all 5 domains of the CAP, most significantly with the sensory domain (r = 0.8971, P = <.0001). No correlation was found between age and severity score. Multiple peroxisomal biochemical parameters were significantly correlated with the severity score. The presently reported severity score for ZSD is a suitable tool to assess phenotypic severity in a ZSD patient at any age. This severity score can be used for objective phenotype descriptions, genotype-phenotype correlation studies, the identification of prognostic features in ZSD patients and for classification and stratification of patients in clinical trials.

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High prevalence of primary adrenal insufficiency in Zellweger spectrum disorders

Cited by 37 publications

References 11 publications

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines

Adrenoleukodystrophy – neuroendocrine pathogenesis and redefinition of natural history

Development and validation of a severity scoring system for Zellweger spectrum disorders

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