Visual loss as first clinical manifestation of X-linked adrenoleukodystrophy / Perda visual como primeira manifestação clínica de adrenoleucodistrofia ligada ao X

Abstract X-linked adrenoleukodystrophy (X-ALD) represents a group of diseases characterized by the accumulation of very long chain fattyacids (VLCFAs) in the tissues. Its clinical manifestations are usually manifold. Visual changes may be present, but they often appear later in the disease. We describe here the case of a 9-year-old boy with X-ALD, whose first symptom was visual loss, which began at 8 years of age. His ophthalmologic evaluation revealed no alterations. Shortly thereafter, he suffered a head injury. The magnetic resonance imaging of brain revealed findings that led to the suspicion of X-ALD. The plasma VLCFA dosage confirmed this diagnosis. This report aims toshow that in cases of visual loss with a normal ophthalmic examination, a high index of suspicion should be given for conditions suchas X-ALD, since it affects the cortical routes related to vision. Fundoscopy findings appear late in X-ALD.

Resumo A adrenoleucodistrofia ligada ao X (X-ALD) representa um grupo de doenças caracterizadas pelo acúmulo de ácidos graxos de cadeia muito longa (VLCFAs) nos tecidos. Suas manifestações clínicas costumam ser múltiplas. Alterações visuais podem estar presentes, contudo costumam surgir mais tardiamente na doença. Descrevemos aqui o caso de um menino de 9 anos com X-ALD, cujo primeiro sintoma foi perda visual, iniciada aos 8 anos de idade. A sua avaliação oftalmológica não revelou alterações. Pouco tempo depois, ele sofreu um traumatismo craniano. A imagem de ressonância magnética de encéfalo revelou achados que levaram a suspeita de X-ALD. A dosagem dos VLCFAs no plasma confirmou este diagnóstico. Este relato tem como objetivo mostrar que em casos de perda visual com um exame oftalmológico normal, deve-se ter um alto índice de suspeita para condições como a X-ALD, pois a mesma afeta as vias corticais relacionadas à visão. Nessa doença, os achados da fundoscopia aparecem mais tardiamente.

X-linked adrenoleukodystrophy in brazil: a case series / Adrenoleucodistrofia ligada ao x no brasil: uma série de casos

ABSTRACT Objective: To describe patients with different phenotypes of X-linked adrenoleukodystrophy: pre-symptomatic, cerebral demyelinating inflammatory adrenoleukodystrophy, adrenomyeloneuropathy and adrenal insufficiency only. Methods: Specific data related to epidemiology, phenotype, diagnosis and treatment of 24 patients with X-linked adrenoleukodystrophy were collected. A qualitative cross-sectional and descriptive-exploratory analysis was performed using medical records from a reference center in Neuropediatrics in Curitiba, Brazil, as well as an electronic questionnaire. Results: The majority (79%) of patients had cerebral demyelinating inflammatory adrenoleukodystrophy, presenting aphasia, hyperactivity and vision disorders as the main initial symptoms. These symptoms appeared, on average, between six and seven years of age. There was a mean delay of 11 months between the onset of symptoms/signs and the diagnosis. Patients sought diagnosis mainly with neuropediatricians, and the main requested tests were dosage of very long chain fatty acids and brain magnetic resonance. Conclusions: All phenotypes of X-linked adrenoleukodystrophy, except for myelopathy in women, were presented in the studied population, which mainly consisted of children and adolescents. Prevalent signs and symptoms registered in the literature were observed. Most of the patients with cerebral demyelinating inflammatory adrenoleukodystrophy were not diagnosed in time for hematopoietic stem cell transplantation.

RESUMO Objetivo: Descrever pacientes com diferentes formas de adrenoleucodistrofia ligada ao X: pré-sintomática, adrenoleucodistrofia inflamatória desmielinizante cerebral, adrenomieloneuropatia e insuficiência adrenal primária. Métodos: Dados específicos relacionados a epidemiologia, fenótipo, diagnóstico e tratamento de 24 pacientes com adrenoleucodistrofia ligada ao X foram coletados. Realizou-se análise qualitativa, transversal e descritivo-exploratória, utilizando prontuários de um centro de referência em neuropediatria de Curitiba, Brasil, além de um questionário eletrônico. Resultados: A maioria (79%) dos pacientes manifestou adrenoleucodistrofia inflamatória desmielinizante cerebral, apresentando afasia, hiperatividade e distúrbios da visão como principais sintomas iniciais, que apareceram, em média, entre seis e sete anos de idade. Houve um atraso médio de 11 meses entre o início das manifestações e o diagnóstico. Os pacientes procuraram diagnóstico principalmente com neuropediatras, e os principais exames solicitados foram dosagem de ácidos graxos de cadeia muito longa e a ressonância magnética de crânio. Conclusões: Todos os fenótipos da adrenoleucodistrofia ligada ao X, exceto mielopatia em mulheres, foram apresentados na amostra estudada, composta principalmente de crianças e adolescentes. Foram observados sinais e sintomas prevalentes na literatura. A maioria dos pacientes com adrenoleucodistrofia inflamatória desmielinizante cerebral não recebeu diagnóstico em tempo hábil para a realização de transplante de medula óssea.

Enfermedad de Addison en un niño con adrenoleucodistrofia ligada al cromosoma X / Primary adrenal failure associated to X-linked adrenoleukodystrophy: report of one case

Primary adrenal failure (PAF) can be congenital or acquired. X-linked adrenoleukodystrophy (ALD-X), produced by the mutation of the ABDC1 gene (Xq28), that leads to the plasma accumulation of very long chain fatty acids, is one of the congenital diseases associated to adrenal destruction. We report a 7 years old boy with fast progression of right strabismus and general symptoms as weariness, weakness and mucosal and skin pigmentation. A brain magnetic resonance image showed a leukoencephalopathy, characteristic of ALD-X. Low plasma cortisol, high ACTH levels and lack of response to ACTH test, confirmed the diagnosis of primary adrenal insufficiency. High plasma levels of C26:0 fatty acids, and C24/22, C26/22 ratios confirmed ALD-X.

Clinical profile of adrenoleukodysrophy.

X-linked Adrenoleukodystrophy (ALD) is the most common of the peroxisomal disorder and is associated with functional defect of the very long chain fatty acid (VLCFA) oxidation leading to the accumulation of VLCFA in the white matter and adrenal cortex. Retrospective evaluation of medical records of ALD patients were carried out. In all the 5 patients the duration of the symptoms varied from 1-7 years. Most of them presented with Addisonian crisis (4/5) and hyperpigmentation (5/5), white half of them (3/5) had neurological symptoms. All patients had biochemical evidence of the adrenal insufficiency. All siblings of patients should be screened for the possibility of ALD with VLCFA.

Adrenal functions in children with adrenoleukodystrophy.

BACKGROUND: Adrenoleukodystrophy refers to an inherited disorder that mainly affects the adrenal gland, and the nervous system. The most common type is X-linked adrenoleukodystrophy (XALD). The main presenting symptoms are behavioral changes. However, endocrinological manifestations are also important and need to be clarified especially adrenal insufficiency which is a lifethreatening condition that can be prevented. OBJECTIVE: To review the endocrinological and the adrenal functions in X-linked ALD. SUBJECTS AND METHOD: The medical records of four patients diagnosed with ALD at the Endocrinology and Metabolic Unit, Department of Pediatrics, King Chulalongkorn Memorial Hospital between 1998 and 2000 were reviewed. The diagnoses were confirmed by elevated very long chain fatty acid (VLCFA) levels and the typical changes seen on magnetic resonance imaging (MRI) of the brain. The adrenal functions in these patients were studied. RESULTS: All patients presented between 7-11 years of age with learning problems and behavioral changes, without symptoms of adrenal insufficiency such as nausea, vomiting and abdominal pain. However, the physical signs of adrenal insufficiency such as generalized hyperpigmentation particularly on the nipples, skin creases and genitalia were present. The laboratory investigations revealed normal blood sugar and serum electrolytes. The adrenal functions were revealed as follows. Basal ACTH levels were high in 2 cases (290, > 1,250 pg/mL). Basal cortisol level was low in 1 case. ACTH stimulation tests revealed subnormal responses in 3 cases. Magnetic Resonance Imaging of the brain showed white matter degeneration in the occipital area in 2 cases and frontal area in 2 cases. CONCLUSION: Adrenal insufficiency can be detected by laboratory evaluation despite the lack of symptoms, therefore, the adrenal function should be evaluated in X-ALD at diagnosis for proper management.

Adrenoleucodistrofia: estudo clínico e histopatológico de um caso associado ao uso de abortivos no segundo mês de gestaçäo / Adrenoleukodystrophy: clinical and histopathological study of a case associated to the use of abortifacient agents in the second month of pregnancy

Os autores descrevem um caso de adrenoleucodistrofia (ALD) em um paciente do sexo masculino, com 8 anos de idade, cuja genitora no primeiro trimestre da gravidez tomou miscelânia de drogas com fins abortivos. O curso da doença foi progressivo iniciando-se por distúrbios auditivos, visuais e mentais, seguindo-se alteraçöes neurovegetativas, motoras, convulsivas e postura fetal. No estágio final o paciente tornou-se amaurótico, surdo, quadriplégico e demente. O óbito ocorreu por infecçäo respiratória. O diagnóstico foi confirmado pelo estudos do LCR, eletrofisiológicos e pelos achados de necrópsia (cérebro e glândulas adrenais)