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X linked adrenoleucodystrophy (X-ALD) is considered to be a rare cause of Addison's disease, although several small series suggest a high incidence in young Addisonian males. A survey in the south west of England identified 12 male patients diagnosed with Addison's disease in the period 1987-99. In 10 of these (83%) X-ALD was the underlying cause;...
Citations
... In our case, the boy experienced vomiting and coma symptoms but received a delayed diagnosis until mucocutaneous pigmentation appeared and plasma VLCFA levels were tested, ultimately confirming X-ALD clinically. It is worth noting that X-ALD may be underdiagnosed in boys with adrenal insufficiency, as one study found that 83% of boys with unexplained adrenal insufficiency had X-ALD [10,11]. Plasma C26:0/C22:0 and C24:0/C22:0 ratios are the diagnostic hallmarks of ALD [12]. ...
X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by the variations in the ATP-binding cassette sub-family D member 1 (ABCD1) gene. This study is the first to report central precocious puberty (CPP) in individuals with X-ALD. A 6-year-old boy exhibited mucocutaneous pigmentation, increased plasma adrenocorticotropic hormone levels, and elevated very long-chain fatty acids (VLCFA). We identified a variant, c.1826A>G (p. Glu609Gly), in exon 8 of the ABCD1 gene in the proband. Additionally, he displayed rapid growth, testicular volume of 5–6 mL, the onset of pubic hair, and pubertal levels of luteinizing hormone (LH), all meeting the diagnostic criteria for CPP.
... Published diagnostic guidelines for PAI include recommended VLCFA testing for males with PAI who are negative for 21hydroxylase (21-OH) antibodies, and concurrent testing for adrenal antibodies and VLCFA through accredited laboratories in preadolescent boys [22]. However, despite these guidelines and older cases or case series highlighting the need to screen children and adult males with unexplained PAI for ALD [23][24][25], a recent study highlights the continued need for education that PAI in the absence of adrenal antibodies should be a red flag for a potential ALD diagnosis. Age related ranges for VLCFA need to be used. ...
Background:
Adrenoleukodystrophy (ALD) is an X-linked, metabolic disorder caused by deficiency of peroxisomal ALD protein resulting in accumulation of very-long chain fatty acids (VLCFA) primarily in the adrenal cortex and central nervous system. Approximately 35-40% of boys with ALD develop cerebral ALD (CALD), which causes rapidly progressive cerebral demyelination, loss of neurologic function, and death. Approximately 70-80% of boys with ALD have impaired adrenal function prior to the onset of neurologic symptoms.
Case report:
We present a boy who had recurrent episodes of hypoglycaemia from age 2 years and was diagnosed with adrenal insufficiency without adrenal antibodies at age 5.5 years.
Results:
Following initial normal VLCFA levels, subsequent VLCFA analysis demonstrated elevated C26 fatty acids consistent with peroxisomal dysfunction and suggestive of ALD, which was confirmed via molecular genetic analysis of the ABCD1 gene. Brain imaging evidence of cerebral involvement emerged at age 7, and the child underwent successful allogeneic hematopoietic stem cell transplantation. At last assessment (11.5 years old), he was performing as expected for age.
Conclusion:
This case highlights the importance of pursuing a diagnosis when clinical suspicion remains, and the significance of VLCFA analysis for patients with adrenal insufficiency without adrenal antibodies in prompting an ALD diagnosis. Subsequent brain imaging surveillance can detect early, pre-symptomatic cerebral disease allowing for timely treatment and successful arrest of cerebral disease progression.
... 4 Isolated adrenal insufficiency (Addison disease only) can occur in 10% of X-ALD cases and may be present in more than 50% of patients with cerebral X-ALD / AMN. 6 The signs of high ACTH secretion may include unexplained vomiting, weakness, coma or hyperpigmentation. X-ALD is a frequent cause of Addison's disease (35%), particularly when circulating adrenocortical autoantibodies are absent. ...
Introduction: X-linked adrenoleukodystrophy is a genetically determined peroxisomal disease. Clinical case: An eleven-year-old boy was referred to a pediatric clinic due to generalized hyperpigmentation beginning at the age of six. By ten years of age he started to present behavior changes and decreased school perfomance. History of cutaneous hyperpigmentation was documented in the boys maternal uncle. Blood tests were compatible with adrenal insufficiency. Brain Magnetic Resonance Imaging showed frontal leukoencephalopathy. The elevated plasmatic concentration of very long-chain fatty acids and the genotype sequencing of ABCD1 gene established the diagnosis of X-linked adrenoleukodystrophy. The boy´s general condition improved with adrenal insufficiency corticoesteroid treatment however progressive cognitive function deterioration was maintained. Discussion/Conclusion: Early diagnosis and treatment of this rare condition is very important as it can change the disease course. In this case report, given the severity of neurological involvement at diagnosis, no treatment was available to halt neurological disease progression.
... O marcador biológico é um defeito da -oxidaç ão dos ácidos gordos de cadeia muito longa que se encontram aumentados. Esta hipótese diagnóstica tem de ser investigada em qualquer crianç a do sexo masculino que se apresente com ISRP idiopática 6 . ...
A insuficiência suprarrenal primária (ISRP) é relativamente rara na infância e adolescência.
... Approximately 50% develop neurological manifestations similar to AMN but have a later onset (age ≥35 years), a milder disease, cerebral disturbance is uncommon and adrenal insufficiency is rare. 9 The diagnosis of X-ALD may be raised by the above clinical signs or symptoms, including isolated adrenal insufficiency and is commonly achieved by laboratory evaluation of increased concentrations of VLCFA in plasma. Testing typically includes three VLCFA parameters: the level of hexacosanoic acid (C26:0), and the ratio of hexacosanoic acid to tetracosanoic acid (C26:0/ C24:0), and to docosanoic acid (C26:0/C22:0). ...
The X linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease caused by defects of the ABCD1 gene on chromosome Xq28 leading to accumulation of very long chain fatty acids (VLCFA), progressive demyelination and adrenal insufficiency. An 8-year-old boy was referred to our paediatric endocrinology clinic due to fatigue and hyperpigmentation with onset at 2-years old. Blood tests revealed mineralocorticoid insufficiency. Serum adrenocorticotropic hormone and cortisol concentrations were compatible with adrenal insufficiency. Adrenal antibodies were negative. The elevated plasmatic concentration of VLCFA and the genotype analysis with sequencing of ABCD1 gene established the diagnosis of X-ALD. Brain MRI showed demyelination of white matter in the peritrigonal regions. Steroid replacement was started with good response. He initiated restriction of VLCFA by reducing the intake of fatty foods. The authors highlight the importance of suspecting of X-ALD in the aetiology of primary adrenal insufficiency as the first sign of the disease.
... ALD is progressive disorder that affects both the adrenal glands and myelin. 1 This is an inherited disorder of peroxisomal metabolism with lack of fatty acyl coenzyme A (acyl CoA) synthetase leading to accumulation of VLCFAs, leading to progressive dysfunction of adrenals, nervous system and testes. Six different phenotypes are possible of which childhood cerebral ALD and adrenomyeloneuropathy are the commonest ones. 2 Addison's disease may precede the development of neurological features of ALD by many years or decades 3 and many have scanty scalp hair 2 like our 4 Other presentations include impaired vision and auditory discrimination, seizures and progressive dementia and subclinical testicular insufficiency and difficulty in urination. Very rarely patients with X-ALD may have symptoms resembling features of spinocerebellar degeneration. ...
... Las causas más frecuentes de insuficiencia suprarrenal primaria en niños varones de países desarrollados son las de etiología autoinmunitaria y la adrenoleucodistrofia. Por lo tanto, es necesario descartarlas antes de catalogarla como idiopática o enfermedad de Addison 3,4 . La infiltración suprarrenal por citomegalovirus es otra causa menos frecuente de insuficiencia suprarrenal primaria que se produce principalmente en pacientes con alteración de la inmunidad celular y origina un aumento de tamaño de las glándulas suprarrenales visibles en las imágenes por TC, lo cual no se corresponde con el caso. ...
X-linked adrenoleukodystrophy is an inherited metabolic disease caused by the accumulation of saturated very long chain fatty acids (VLCFA). Given that the form of presentation can be primary adrenal insufficiency, diagnosis in affected males is important. Patient was a 4-year-old boy with attention deficit hyperactivity disorder, cutaneous-mucosal hyperpigmentation, and dehydration with hyponatremia and hyperpotassemia was diagnosed with adrenoleukodystrophy presenting as primary adrenal insufficiency. Antiadrenal antibodies: negative. Plasma VLCFA: C(26:0)=1.25mg/ml (0.18-0.48), C(24:0)/C(22:0) =1.53 (< 1), and C(26:0)/ C(22:0)=0.04 (< 0.02). Abdominal computed tomography: small adrenal glands. Cranial magnetic resonance imaging and evoked potentials: normal at diagnosis and with signs of white matter demyelination after 2 years of follow-up. Testing for an autoimmune etiology and adrenoleukodystrophy is important in boys with primary adrenal insufficiency before Addison's disease is diagnosed.
... Las causas más frecuentes de insuficiencia suprarrenal primaria en niños varones de países desarrollados son las de etiología autoinmunitaria y la adrenoleucodistrofia. Por lo tanto, es necesario descartarlas antes de catalogarla como idiopática o enfermedad de Addison 3,4 . La infiltración suprarrenal por citomegalovirus es otra causa menos frecuente de insuficiencia suprarrenal primaria que se produce principalmente en pacientes con alteración de la inmunidad celular y origina un aumento de tamaño de las glándulas suprarrenales visibles en las imágenes por TC, lo cual no se corresponde con el caso. ...
X-linked adrenoleukodystrophy is an inherited metabolic disease caused by the accumulation of saturated very long chain fatty acids (VLCFA). Given that the form of presentation can be primary adrenal insufficiency, diagnosis in affected males is important. Patient was a 4-year-old boy with attention deficit hyperactivity disorder, cutaneous-mucosal hyperpigmentation, and dehydration with hyponatremia and hyperpotassemia was diagnosed with adrenoleukodystrophy presenting as primary adrenal insufficiency. Antiadrenal antibodies: negative. Plasma VLCFA: C26:0 = 1.25 mg/ml (0.18-0.48), C24:0/C22:0 =1.53 (< 1), and C26:0/ C22:0 = 0.04 (< 0.02). Abdominal computed tomography: small adrenal glands. Cranial magnetic resonance imaging and evoked potentials: normal at diagnosis and with signs of white matter demyelination after 2 years of follow-up.
Testing for an autoimmune etiology and adrenoleukodystrophy is important in boys with primary adrenal insufficiency before Addison's disease is diagnosed.
... Em 80% a 90% dos casos, os sinais endócrinos precedem os sintomas neurológicos (81,82). Portanto, a possibilidade de ALD deve ser suspeitada em meninos com doença de Addison, mesmo na ausência de demência ou distúrbio neurológico progressivo (83). ...
Thomas Addison first described, 150 years ago, a clinical syndrome characterized by salt-wasting and skin hyperpigmentation, associated with a destruction of the adrenal gland. Even today, over a century after Addison's report, primary adrenal insufficiency can present as a life-threatening condition, since it frequently goes unrecognized in its early stages. In the 1850s, tuberculous adrenalitis was present in the majority of patients, but nowadays, autoimmune Addison's disease is the most common cause of primary adrenal insufficiency. In the present report, we show the prevalence of different etiologies, clinical manifestations and laboratorial findings, including the adrenal cortex autoantibody, and 21-hydroxylase antibody in a Brazilian series of patients with primary adrenal insufficiency followed at Divisão de Endocrinologia da Universidade Federal de São Paulo (UNIFESP) and at Faculdade de Medicina de Ribeirão Preto-USP (FMRP-USP).
... Cerebral x-linked adrenoleukodystrophy (X-ALD) X-ALD 47,48 is a peroxisomal disorder involving defective boxidation of very long-chain fatty acids (VLCFA). Phenotypes vary in severity from pure Addisonian presentations without obvious CNS involvement, 49 through the insidious adult-onset form (adrenomyeloneuropathy (AMN)), adolescent and adult onset cerebral X-ALD to the rapidly dementing and fatal childhood onset cerebral form at most severe. Approximately 40% of boys with X-ALD will develop childhood cerebral disease. ...
For the past two decades, hematopoietic cell transplantation (HCT) has been used as effective therapy for selected inherited metabolic diseases (IMD) including Hurler (MPS IH) and Maroteaux-Lamy (MPS VI) syndromes, childhood-onset cerebral X-linked adrenoleukodystrophy (X-ALD), globoid-cell leukodystrophy (GLD), metachromatic leukodystrophy (MLD), alpha-mannosidosis, osteopetrosis, and others. Careful pre-HCT evaluation is critical and coordinated, multidisciplinary follow-up is essential in this field of transplantation. The primary goals of HCT for these disorders have been to promote long-term survival with donor-derived engraftment and to optimize the quality of life. Guidelines for HCT and monitoring are provided; a brief overview of long-term results is also presented.
