1/205. Case studies: psychological test findings for two children with X-linked adrenoleukodystrophy. Psychological evaluations were performed on two children with X-linked adrenoleukodystrophy. Case histories are presented that describe the natural history of the disorder and its symptom patterns, some of which mirror psychiatric disorders of childhood. Psychological evaluation test scores for both boys are displayed in a table, and commonalities and differences are discussed. Findings are reviewed to expedite the referral process for a definitive diagnosis. Guidelines are provided regarding the differential diagnosis of adrenoleukodystrophy and other neurodegenerative disorders of childhood from the more prevalent disorders of behavior and learning that may present in a developmental clinic. Finally, recommendations for psychological interventions with the affected child and family members are provided. ( info) |
| adrenoleukodystrophy (ALD) is an X-linked disorder of metabolism of very long chain fatty acids (VLCFAs) with a frequency of up to 1:20,000 in males. VLCFAs C24:0 and C26:0 accumulate in the cholesterol ester and ganglioside fraction in plasma and red cells. Symptoms of ALD are ataxia, loss of visual and auditory functions, and cerebral convulsions. Up to the present, no sure therapeutic approaches have been established. Efforts were reported by dietary regimens with VLCFA restriction and glyceroltrioleate and glyceroltrierucate intake. In the present trial, we report a 55-year-old Caucasian male suffering from progressive ALD with spastic paraparesis. He has had a positive family history since the eighteenth century. In this patient treated with maximum dietary therapy over a period of 60 months, no normalization of C24:0 and C26:0 was reached, and neurological disorders were progressive. As a result, plasmapheresis was applied during the period 1990-1994 and since then for more selective adsorption of VLCFAs, dextran sulfate adsorption (Liposorber, Kaneka, japan). During this period (64 months), C24:0 and C26:0 levels were reduced by 54.5% and 51.8%, respectively (p = 0.0001). The patient experienced a significant improvement in performance and general well-being. There has been no further progression of neuronal disorders to document. ( info) |
| amniocentesis was performed at 17 weeks' gestation on a 39-year-old woman at risk of being a carrier for X-linked adrenoleukodystrophy (X-ALD). Her first son had been affected with childhood cerebral X-ALD and had died at the age of nine years. dna analysis had not been performed nor was any material available. The amniotic fluid cells (AFC) karyotype was found to be male and initial determination of very long chain fatty acids (VLCFA) in cultured amniocytes revealed borderline values. As an alternative strategy the complete coding region of the ALD gene was amplified and sequenced using dna isolated from both AFC and maternal leukocytes as templates. Sequencing of the mother's dna revealed the heterozygous pattern of a 2 bp deletion in exon 5, the most frequent individual mutation leading to X-ALD. It has previously been described to result in a complete loss of protein. This deletion was excluded in the fetus. Accordingly, ALDP was readily detected in AFC by immunofluorescence. We conclude that under circumstances of incomplete data about the index case the combination of methods, namely dna analysis of the heterozygous mother, and biochemical, immunocytochemical and dna analyses in fetal cells can secure a reliable prenatal diagnosis of X-ALD. ( info) |
4/205. Two novel missense mutations causing adrenoleukodystrophy in Italian patients. The authors present two new missense mutations in exon 1 of the adrenoleukodystrophy (ALD) gene. The first, a C813T transition, results in the substitution Pro143 Ser in the third putative transmembrane domain of the adrenoleukodystrophy protein (ALDP) in an adult onset case. The second, a de novo C709T transition, results in a substitution Ser 108 Leu between the second and the third putative transmembrane segments, in a childhood case. ( info) |
5/205. Two novel frameshift mutations in the adrenoleukodystrophy gene in Italian patients. Two novel frameshift adrenoleukodystrophy mutations in two families were identified: a complex dinucleotide deletion/tetranucleotide insertion at 1116 TC-->GAGA (codon 244 [serine]) and an AG deletion at nucleotide 1462 (codon 359 [glutamic acid]). Both mutations are predicted to cause premature termination of protein synthesis. The patients were affected by childhood cerebral adrenoleukodystrophy and by adrenomyeloneuropathy with mild addison disease, respectively. ( info) |
| A 13-year-old boy with cervical kyphosis was diagnosed as having juvenile alexander disease because of the typical MRI findings, abnormally elevated alphaB-crystallin and heat shock protein 27 in the cerebrospinal fluid. Positron emission tomography with 18F-fluorodeoxyglucose demonstrated hypometabolism in the frontal white matter corresponding to the areas with leukodystrophy. However, the overlying gray matter preserved normal glucose metabolism. ( info) |
7/205. Late-onset adrenoleukodystrophy associated with long-standing psychiatric symptoms. BACKGROUND: It is not commonly appreciated that patients with adrenoleukodystrophy (ALD) can first present in adulthood with psychiatric symptoms. METHOD: This case study involved a 31-year-old man who was referred for a neuropsychiatric assessment of tardive dyskinesia and treatment-resistant psychosis. Upon neurologic examination, he was found to have spasticity, marked hyperreflexia with clonus, and bilateral Babinski signs. T2-weighted magnetic resonance imaging demonstrated severe white matter disease. Metabolic screening revealed abnormalities of very long chain fatty acids consistent with the diagnosis of ALD. These results prompted us to review the literature on late-onset ALD with attention to (1) the nature of the associated psychiatric and neurologic symptoms, (2) the neuroimaging abnormalities associated with this disorder, and (3) treatment considerations. RESULTS: Individuals with adult-onset ALD may initially present with psychiatric symptomatology. Most commonly, these patients manifest signs of mania including disinhibition, impulsivity, increased spending, hypersexuality, loudness, and perseveration. ALD patients will often have upper motor neuron findings on neurologic examination. Despite the name of the disease, patients with ALD may not have clinical evidence of adrenal dysfunction. neuroimaging reveals diffuse, confluent white matter lesions that typically originate in the parieto-occipital region. Both neuroleptic and anticholinergic medications may result in significant side effects with little resolution of the underlying psychiatric symptoms. CONCLUSION: This case study and review of the literature illustrate the importance of performing neurologic and radiological examinations on all psychiatric patients with chronic illnesses. We emphasize the importance of reexamining and reimaging patients who are not responding to standard treatment. The clinical problem of "treatment resistance" should be seen as an indication that other diagnoses, such as an underlying metabolic disorder, need to be considered. ( info) |
8/205. X-linked adrenoleukodystrophy: spinocerebellar variant. The phenotypic variability in X-linked adrenoleukodystrophy (X-ALD) can be wide and varied. Rarely, it can present with clinical signs of spinocerebellar degeneration. There are very few reported cases of selective predominant white matter disease of the cerebellum in these patients. We report a patient with a rare variant of adult onset ALD who was previously diagnosed as spinocerebellar ataxia. He was a 24-year-old male who had delayed developmental milestones, developed signs of spinocerebellar degeneration (SCD) after 10 years of Addison's disease. Serial magnetic resonance imaging (MRI), revealed cerebellar and pontine white matter disease but sparing the cerebral cortex and supratentorial white matter. His diagnosis of X-ALD was subsequently confirmed by the elevated serum very long chain fatty acids. This patient illustrates the unusual clinical presentation and imaging features of X-ALD and the importance of considering X-ALD in the clinical context of spinocerebellar degeneration. Early recognition of this rare variant would allow proper genetic counselling and institution of dietary therapy and/or bone marrow transplantation. ( info) |
| The clinical course of a 6-year-old boy with adrenoleukodystrophy (ALD) who underwent allogeneic stem-cell transplantation during an early clinical stage is described. Twenty-three months after transplant, he remains neurologically stable, but with moderate neurological sequelae; the serum very long chain fatty acid profile has improved, but not normalized. The indications, mechanism of action, and complications of bone marrow transplantation in ALD are discussed briefly, along with other potential therapies. ( info) |
| adrenoleukodystrophy (ALD) is an X-linked inherited disorder of lipid metabolism usually presenting in childhood or early adolescence. It is a progressive disease with symptoms of adrenal insufficiency and central nervous system demyelination. The pathology results from the accumulation of very long-chain fatty acids and an inflammatory reaction in the brain white matter. We report a case of ALD associated with adrenal insufficiency and two autoimmune diseases: vitiligo and ulcerative colitis. ( info) |