Explore the vast range of titles available.

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. These clinical recommendations are intended to address screening for adrenal insufficiency in boys identified to have ALD by newborn screen. 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. 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. 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.

Nephrotic syndrome is a common condition characterized by filtration of large amounts of protein, hypoalbuminemia, reduced plasma oncotic pressure, sodium retention, and edema. The mechanism responsible for sodium retention in this condition is still controversial. Two different pathophysiological pathways have been proposed to explain edema formation: activation of neurohumoral effector mechanisms, including the renin–angiotensin–aldosterone system, or abnormal intrinsic/primary renal sodium retention. A 5-year-old boy with X-linked adrenoleukodystrophy presented with bilateral leg swelling, massive proteinuria, and hypoalbuminemia. Minimal change disease was diagnosed. The patient was initially treated with corticosteroids and experienced several relapses. The progression of fractional excretion of sodium correlated with proteinuria and undetectable aldosterone levels. This unusual finding suggests that the mechanism of tubular sodium avidity in this child with mineralocorticoid insufficiency was independent of the renin–angiotensin–aldosterone system.

X-linked adrenoleukodystrophy (X-ALD) is a puzzling inborn error of metabolism with a strikingly heterogeneous clinical spectrum. All patients have mutations in the ABCD1 gene and accumulate very long chain fatty acids in all tissues. Virtually all male X-ALD patients develop adrenocortical insufficiency in childhood and progressive myelopathy and peripheral neuropathy in adulthood. A subset of male patients, however, develops a fatal cerebral demyelinating disease, cerebral adrenoleukodystrophy. Female patients also develop progressive myelopathy and peripheral neuropathy, but generally at a later age than males. They only very rarely develop adrenocortical insufficiency or cerebral adrenoleukodystrophy. This review proposes to simplify the classification of the clinical spectrum of X-ALD and reviews the largely unresolved pathophysiological mechanisms and the current treatment options.

Background Progressive myelopathy is the main cause of disability in adrenoleukodystrophy (ALD). Development of therapies is hampered by a lack of quantitative outcome measures. In this study, we investigated whether myelopathy in ALD is associated with retinal neurodegeneration on optical coherence tomography (OCT), which could serve as a surrogate outcome measure. Methods Sixty-two patients (29 men and 33 women) and 70 age-matched and sex-matched controls (33 men and 37 women) were included in this cross-sectional study. We compared retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness between ALD patients and controls. In addition, we correlated these OCT measurements with clinical parameters of severity of myelopathy. Results Patients had significantly thinner RNFL (male group, p  < 0.05) and pRNFL superior and temporal quadrant [both male ( p  < 0.005) and female ( p  < 0.05) groups] compared to controls. Comparing three groups (symptomatic patients, asymptomatic patients and controls), there were significant differences in RNFL thickness (total grid and peripheral ring) in the male group ( p  ≤ 0.002) and in pRNFL thickness (superior and temporal quadrant) in both male ( p  ≤ 0.02) and the female ( p  ≤ 0.02) groups. Neuroretinal layer thickness correlated moderately with severity of myelopathy in men (correlation coefficients between 0.29–0.55, p  < 0.02), but not in women. Conclusions These results suggest that neurodegeneration of the spinal cord in ALD is reflected in the retina of patients with ALD. Therefore, OCT could be valuable as an outcome measure for the myelopathy of ALD. Additional longitudinal studies are ongoing.

Adrenoleukodystrophy (ALD) is a rare and progressive neurogenetic disease that may manifest disparate symptoms. The present study aims at investigating the role of ataxic variant of ALD (AVALD) in patients with adult-onset cerebellar ataxia, as well as characterizing their clinical features that distinguish AVALD from other cerebellar ataxias. Mutations in the ATP binding cassette subfamily D member 1 gene (ABCD1) were ascertained in 516 unrelated patients with ataxia. The patients were categorized into three groups: molecularly unassigned hereditary ataxia (n = 118), sporadic ataxia with autonomic dysfunctions (n = 296), and sporadic ataxia without autonomic dysfunctions (n = 102). Brain MRIs were scrutinized for white matter hyperintensity (WMH) in the parieto-occipital lobes, frontal lobes, corticospinal tracts, pons, middle cerebellar peduncles and cerebellar hemispheres. Two ABCD1 mutations (p.S108L and p.P623fs) previously linked to cerebral ALD and adrenomyeloneuropathy but not AVALD were identified. ALD accounts for 0.85% (1/118) of the patients with molecularly unassigned hereditary ataxia and 0.34% (1/296) of the patients with sporadic ataxia with autonomic dysfunctions. WMH in the corticospinal tracts and WMH in the cerebellar hemispheres were strongly associated with AVALD rather than other ataxias. To conclude, ALD accounts for approximately 0.39% (2/516) of adult-onset cerebellar ataxias. This study expands the mutational spectrum of AVALD and underscores the importance of considering ALD as a potential etiology of cerebellar ataxia.

Background X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder. Male patients develop adrenocortical insufficiency (80 % before 18 years), a chronic myelopathy (adrenomyeloneuropathy (AMN); all in adulthood), or progressive cerebral demyelination (cerebral ALD; 40 % before 18 years). Cerebral ALD is treated with haematopoetic cell transplantation (HCT). It is unknown if AMN still develops in patients with X-ALD that underwent HCT for cerebral ALD in childhood. Patients and methods A retrospective observational study was performed by selecting all adult patients with X-ALD in our cohort that underwent HCT in childhood. Results This retrospective study found that three out of five patients in our cohort who underwent HCT in childhood developed signs of myelopathy in adulthood. Conclusion These data suggest that HCT for cerebral ALD in childhood does not prevent the onset of AMN in X-ALD in adulthood.

This case presentation outlines the occurrence of primary adrenal insufficiency secondary to ATP binding cassette subfamily D member 1 (ABCD1) mutation in a man in his 40s following a genetic screening test performed after a diagnosis of X-linked adrenoleukodystrophy (X-ALD) in his nephew who is in his middle childhood years. In contrast to his nephew’s presentation with rapid onset and progression of cerebral adrenoleukodystrophy leading to severe neurological manifestations, his symptoms primarily included chronic fatigue and muscle stiffness without any features suggestive of mineralocorticoid deficiency noted for at least 3 years preceding the timeline of his diagnosis. Genetic testing revealed X-ALD (hemizygous for ABCD1:c901-5c>A). A short synacthen test confirmed primary adrenocortical insufficiency. Hydrocortisone treatment was initiated, leading to improvement in symptoms. His presentation highlights the well-recognised but less commonly perceived implications of ABCD1 mutation and its relevance in routine clinical practice as a part of diagnostic tests for primary adrenal insufficiency.

Adrenoleukodystrophy (ALD) is a fatal progressive neurodegenerative disorder affecting brain white matter. The most common form of ALD is X-linked (X-ALD) and results from mutation of the ABCD1-encoded very long chain fatty acid (VLCFA) transporter. X-ALD is clinically heterogeneous, with the cerebral form being the most severe. Diagnosed in boys usually between the ages of 4 and 8, cerebral X-ALD symptoms progress rapidly (in as little as two years) through declines in cognition, learning, and behavior, to paralysis and ultimately to a vegetative state and death. Currently, there are no good treatments for X-ALD. Here we exploit the Drosophila bubblegum (bgm) double bubble (dbb) model of neurometabolic disease to expand diagnostic power and therapeutic potential for adrenoleukodystrophy. We show that loss of the Drosophila long/very long chain acyl-CoA synthetase genes bgm and/or dbb is indistinguishable from loss of the Drosophila ABC transporter gene dABCD1. Shared loss-of-function phenotypes for synthetase and transporter mutants point to a lipid metabolic pathway association with ALD-like neurodegenerative disease in Drosophila; a pathway association that has yet to be established in humans. We also show that manipulation of environment increases the severity of neurodegeneration in bgm and dbb flies, adding even further to a suite of new candidate ALD disease-causing genes and pathways in humans. Finally, we show that it is a lack of lipid metabolic pathway product and not (as commonly thought) an accumulation of pathway precursor that is causative of neurometabolic disease: addition of medium chain fatty acids to the diet of bgm or dbb flies prevents the onset of neurodegeneration. Taken together, our data provide new foundations both for diagnosing adrenoleukodystrophy and for designing effective, mechanism-based treatment protocols.

Recurrent episodes of vomiting and diarrhoea in a child can present as a diagnostic dilemma and be easily misdiagnosed as recurrent viral gastroenteritis episodes. Primary adrenal insufficiency can present with recurrent episodes of vomiting and diarrhoea with the presence of metabolic acidosis and can be life-threatening if left undiagnosed and untreated. A high index of suspicion should be kept for diagnosing primary adrenal insufficiency in a child presenting with recurrent episodes of vomiting and diarrhoea with laboratory evidence of metabolic acidosis and hypoglycaemia. Primary adrenal insufficiency, in a male child specifically, should raise alarm for X-linked adrenoleukodystrophy (X-ALD). Very-long-chain fatty acids and confirmatory genetic testing for an ABCD1 gene mutation can help confirm the diagnosis. Addison’s disease often presents prior to the onset of the cerebral form of X-ALD. Early diagnosis of X-ALD allows for MRI screening for the development of cerebral disease in its early stages when treatment with stem cell transplant can halt the disease and be lifesaving.