ESPEYB20 6. Adrenals Important for Clinical Practice (3 abstracts)
6.5. International recommendations for the diagnosis and management of patients with adrenoleukodystrophy: A consensus-based approach
Engelen M , van Ballegoij WJC , Mallack EJ , Van Haren KP , Köhler W , Salsano E , van Trotsenburg ASP , Mochel F , Sevin C , Regelmann MO , Tritos NA , Halper A , Lachmann RH , Davison J , Raymond GV , Lund TC , Orchard PJ , Kuehl JS , Lindemans CA , Caruso P , Turk BR , Moser AB , Vaz FM , Ferdinandusse S , Kemp S , Fatemi A , Eichler FS & Huffnagel IC
Neurology. 2022; 99(21): 940–951.PMID: 36175155. https://pubmed.ncbi.nlm.nih.gov/36175155/
Brief summary: This paper describes consensus expert recommendations for the diagnosis and management of patients with Adrenoleukodystrophy.
Adrenoleukodystrophy (ALD), a progressive metabolic disorder with variable and unpredictable clinical course, is caused by pathogenic variants in ABCD1 gene leading to deficient β-oxidation of saturated very-long-chain fatty acids (VLCFAs) (1, 2). Patients are asymptomatic at birth but develop symptoms as the disease progresses. There are 3 core clinical syndromes: a slowly progressive myeloneuropathy (adrenomyeloneuropathy), a rapidly progressive leukodystrophy (cerebral ALD), and primary adrenal insufficiency. Women develop myeloneuropathy, while men can develop all 3 syndromes (3, 4). These syndromes are not present in all individuals and are not related to genotype. Cerebral ALD and adrenal insufficiency require early detection and intervention and warrant clinical surveillance because of variable penetrance and age at onset. Newborn screening has increased the number of presymptomatic individuals under observation, but clinical surveillance protocols vary.
This paper describes a consensus-based modified Delphi approach among 28 international ALD experts to develop best-practice recommendations for diagnosis, clinical surveillance, and treatment of patients with ALD. They identified 39 discrete areas of consensus. Regular monitoring to detect the onset of adrenal failure and conversion to cerebral ALD is recommended in all male patients. Hematopoietic cell transplant (HCT) is the treatment of choice for cerebral ALD. This guideline addresses a clinical need in the ALD community worldwide as the number of overall diagnoses and presymptomatic individuals is increasing because of newborn screening and greater availability of next-generation sequencing. The poor ability to predict the disease course informs current monitoring intervals but remains subject to change as more data emerge. This knowledge gap should direct future research and illustrates once again that international collaboration among physicians, researchers, and patients is essential to improving care.
References: 1. Kemp S, Huffnagel IC, Linthorst GE, Wanders RJ, Engelen M. Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history. Nat Rev Endocrinol. 2016; 12(10): 606-615. 2. Mosser J, Douar AM, Sarde CO, et al. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature. 1993; 361(6414):726-730. 3. Huffnagel IC, Dijkgraaf MGW, Janssens GE, et al. Disease progression in women with X-linked adrenoleukodystrophy is slow. Orphanet J Rare Dis. 2019; 14(1):30. 4. Habekost CT, Schestatsky P, Torres VF, et al. Neurological impairment among heterozygote women for X-linked Adrenoleukodystrophy: a case control study on a clinical, neurophysiological and biochemical characteristics. Orphanet J Rare Dis. 2014; 9:6.
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ESPE Yearbook of Paediatric Endocrinology
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