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At least 19 recordsLinked to original sources
PubMed1989

Adrenoleukodystrophy. The chain shortening of erucic acid (22:1(n-9)) and adrenic acid (22:4(n-6)) is deficient in neonatal adrenoleukodystrophy and normal in X-linked adrenoleukodistrophy skin fibroblasts.

The metabolism of long chain unsaturated fatty acids was studied in cultured fibroblasts from patients with X-linked adrenoleukodystrophy (ALD) and with neonatal ALD. By using [14-14C] erucic acid (22:1(n-9)) as substrate it was shown that the peroxisomal beta-oxidation, measured as chain shortening, was impaired in cells from patients with neonatal ALD. The beta-oxidation of adrenic acid (22:4(n-6)), measured as acid-soluble products, was also reduced in the neonatal ALD cells. The peroxisomal beta-oxidation of [14-14C]erucic acid (22:1(n-9)) and [2-14C]adrenic acid (22:4(n-6)) was normal in cells from X-ALD patients. The beta-oxidation, esterification and chain elongation of [1-14C]arachidonic acid (20:4(n-6)) and [1-14C]eicosapentaenoic acid (20:5(n-3)) was normal in both X-linked ALD and in neonatal ALD. Previous studies suggest that the activation of very long chain fatty acids by a lignoceryl (24:0)-CoA ligase is deficient in X-linked ALD, while the peroxisomal beta-oxidation enzymes are deficient in neonatal ALD. The present results suggest that the peroxisomal very long-chain acyl-CoA ligase is not required for activation of unsaturated C20 and C22 fatty acids and that these fatty acids can be efficiently activated by the long chain acyl-(palmityl)-CoA ligase.

Adrenoleukodystrophy↗
PubMed1991

Adrenoleukodystrophy: a correlation between saturated very long-chain fatty acids in mononuclear cells and phenotype.

Saturated very long-chain fatty acids in erythrocyte membranes, blood plasma, and mononuclear cells were studied in 4 patients with childhood-adolescent adrenoleukodystrophy and 4 patients with adult adrenoleukodystrophy and 19 normal control subjects by using high-performance liquid chromatography. Ratios of C26:0 to C22:0 in mononuclear cells, erythrocyte membranes, and blood plasma in patients with childhood-adolescent and adult adrenoleukodystrophy were significantly higher than in normal control subjects. Furthermore, ratios of C26:0 to C22:0 in mononuclear cells were significantly higher in patients with childhood-adolescent adrenoleukodystrophy than in patients with adult adrenoleukodystrophy, whereas there was no significant difference in the ratios in erythrocyte membranes and blood plasma between the two groups of patients with adrenoleukodystrophy. These results suggest that there is a correlation between phenotype and ratio of C26:0 to C22:0 within mononuclear cells in patients with adrenoleukodystrophy.

Adolescent↗
PubMed1987

Adrenoleukodystrophy: biochemical procedures in diagnosis, prevention and treatment.

The childhood form of adrenoleukodystrophy is an X-linked recessive disorder which is characterized biochemically by elevated concentrations of saturated very long chain fatty acids in tissues and plasma and impaired very long chain fatty acid oxidation in fibroblasts and leukocytes from adrenoleukodystrophy patients. The most consistently observed increase is that in hexacosanoic acid (C26:0); thus, measurement of plasma C26:0 concentration by gas-liquid chromatography provides a rapid, sensitive method of diagnosis. Prenatal diagnosis of adrenoleukodystrophy can be made by measurement of C26:0 concentrations in amniocytes and chorionic villus cells. Heterozygote (carrier) detection has also been accomplished by biochemical measurement of C26:0 in plasma and skin fibroblasts. In a study of over 200 obligate heterozygotes, greater than 90% showed abnormal concentrations of C26:0. Hybridization studies using the cloned DNA fragment St14 detects polymorphisms in the distal end of the long arm of the X chromosome (Xq27-28) and six informative kindreds have shown co-segregation of adrenoleukodystrophy and the St14 marker through 65 meioses. Thus, such studies can supplement very long chain fatty acid concentrations in heterozygote detection. Therapeutic interventions for adrenoleukodystrophy, such as dietary restriction of very long chain fatty acids, administration of clofibrate or carnitine, immunosuppression and adrenal hormone replacement, have not been successful. Recently, a modification of the very long chain fatty acid-restricted diet has been employed in which this diet is supplemented with synthetic glycerol trioleate. The rationale for this diet is that decreased very long chain fatty acid synthesis by fibroblasts from patients with adrenoleukodystrophy was observed when oleic acid was added to the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenoleukodystrophy↗
PubMed1978

Metabolic studies of adrenoleukodystrophy.

Two series of metabolic studies were prompted by the previous finding that the brain and adrenal tissues of patients with adrenoleukodystrophy, an X-linked genetic disorder, contain unusually long-chain (C22--C32) fatty acids in cholesterol esters and gangliosides. Postmortem brain tissues from three patients were assayed for activities of the three distinct cholesterol ester hydrolases, using [4-14C]cholesterol oleate, lignocerate and cerotate as the substrates. No deficiency of the crude mitochrondrial (pH 4.2), the microsomal (pH 6.0), or the myelin-localized cholesterol ester hydrolases was detected, although the activities of the myelin-localized cholesterol ester hydrolase against cholesteryl lignocerate and cerotate were too low for reliable assays. The activities of the microsomal and myelin-localized hydrolases were actually higher in adrenoleukodystrophy than in controls. Uptake and exclusion by cultured fibroblasts of [1-14C]stearic, [1-14C]lignoceric and [1-14C)cerotic acids were also examined. All fatty acids were avidly taken up by the fibroblasts. Stearic acid was excluded from the cells much more rapidly than lignoceric or cerotic acid. No difference was observed in the uptake and exclusion of fatty acids between the controls and adrenoleukodystrophy, except that cells from some cases of adrenoleukodystrophy consistently took up the very long chain fatty acids at greater rates than the control cells. Neither did the distribution of the label among individual lipids reveal differences between the controls and adrenoleukodystrophy, although there were interesting and dramatic differences in the metabolism of lignoceric acid and cerotic acid. Cerotic acid appeared largely inert with 90--95% remaining intact over eight days, while lignoceric acid was mostly incorporated into complex lipids. This series of studies did not uncover the fundamental genetic defect underlying adrenoleukodystrophy.

Biological Transport↗
PubMed1989

A pathological study of a peripheral nerve in a case of neonatal adrenoleukodystrophy.

The pathological findings for a sural nerve biopsy specimen in a case of neonatal adrenoleukodystrophy are described. The density and total number of myelinated fibers in the patient showed no significant changes compared with controls. On electric microscopy, however, thickness of the myelin was smaller in the patient than in controls. Some linear or trilamellar inclusion bodies were found in Schwann cells and fibroblasts, similar to those found in X-linked adrenoleukodystrophy. Büngner's bands were also seen on electron microscopy, and myelin ovoids and balls were seen in teased fibers. These results show that a sural nerve biopsy is useful for the diagnosis of neonatal adrenoleukodystrophy. We suspect that axonal or neuronal degeneration occurs with changes in myelin in neonatal adrenoleukodystrophy.

Adrenoleukodystrophy↗
PubMed1991

Immunochemical and biochemical studies of fatty acid oxidation in fibroblasts of Zellweger and X-linked adrenoleukodystrophy patients.

Immunoblot analyses of peroxisomal beta-oxidation enzymes showed that subunit A of acyl-CoA oxidase gave a stronger immunoreaction in fibroblasts of Zellweger and X-linked adrenoleukodystrophy patients than in those of controls. Subunits B and C and 3-ketoacyl-CoA thiolase were detected in fibroblasts of controls and X-linked adrenoleukodystrophy patients, but not of Zellweger patients. Total oxidation of palmitic and lignoceric acid was normal in homogenates of fibroblasts from Zellweger and X-linked adrenoleukodystrophy patients. The peroxisomal oxidation of both acids was only deficient in Zellweger patients. These data may not reflect the situation in vivo, as is evident from the accumulation of very-long-chain fatty acids in Zellweger and X-linked adrenoleukodystrophy patients.

Acetyl-CoA C-Acyltransferase↗
PubMed1989

A comparison of erythrocytes, lymphocytes and blood plasma as samples in fatty acid analysis for the diagnosis of adrenoleukodystrophy.

We studied the very-long-chain fatty acids of blood plasma, erythrocyte membranes and lymphocytes in 4 adrenoleukodystrophy patients, 5 adrenoleukodystrophy obligate carriers, 12 normal controls and 81 patients with various neurological disorders by high-performance liquid chromatography and compared the reliabilities in the diagnosis of adrenoleukodystrophy of these 3 components of peripheral blood. Of 81 patients with various neurological disorders, 2 myotonic dystrophy and 2 spinocerebellar degeneration patients showed increased ratios of C26:0 to C22:0 in erythrocyte membranes, but not in blood plasma and lymphocytes. None of the 12 normal controls showed increased ratios of C26:0 to C22:0 in erythrocyte membranes, blood plasma and lymphocytes. These results suggest that fatty acid analysis for the diagnosis of adrenoleukodystrophy is more reliable when blood plasma and lymphocytes are used than when erythrocyte membranes are used.

Adolescent↗
PubMedDate not supplied

Variable phenotypes in a family kindred with adrenoleukodystrophy.

Adrenoleukodystrophy, an X-linked recessive disorder characterized by progressive demyelination of the central nervous system and adrenal insufficiency, usually manifests at 4-8 years of age. We report a 20-month-old male who presented with the sudden onset of status epilepticus and cortical blindness; initially, he had complete resolution of these findings, but experienced a relapse 3 months later. The initial computed tomographic scans depicted cerebral edema and possible "watershed infarcts:" however, over the next 2 weeks before discharge from the hospital, the cortical blindness and ataxia both resolved. During the next 2 months, he exhibited no symptoms: he had no seizures and his neurologic examinations were normal. Three months after the initial hospitalization, he developed what the mother believed was "a weakness on his right side." Magnetic resonance imaging confirmed severe white matter disease. Adrenoleukodystrophy was clinically suspected and an assay of plasma levels confirmed an elevation of C26 long-chain saturated fatty acid levels. After the patient's diagnosis of adrenoleukodystrophy was confirmed, long-chain fatty acid levels were obtained on his 5-year-old brother and his mother. This child had the earliest known onset of X-linked adrenoleukodystrophy.

Adrenoleukodystrophy↗
PubMed1986

Accumulation and defective beta-oxidation of very long chain fatty acids in Zellweger's syndrome, adrenoleukodystrophy and Refsum's disease variants.

The accumulation of very long chain fatty acids in plasma and skin fibroblasts was measured in at least four separate inherited disease states. Both the magnitude and the nature of the fatty acid changes reflected the clinical status of individual patients. In Zellweger's syndrome, and to a lesser extent in infantile Refsum's disease, there was an increase in 24:0, 26:0, 26:1, and a number of even longer chain fatty acids, while in the X-linked form of adrenoleukodystrophy these changes were less pronounced. Zellweger fibroblasts in culture took up lignoceric, phytanic and stearic acids and incorporated them into a variety of lipids in a manner comparable to control fibroblasts. However, these cells were unable to convert phytanic or lignoceric acid to CO2. Infantile Refsum's and X-linked adrenoleukodystrophy fibroblasts showed normal conversion of these acids to CO2. Normal fibroblast homogenates produced radioactive acetate from [1-14C] stearic and [1-14C] lignoceric acids indicating that both substrates were beta-oxidised under these conditions. Homogenates of fibroblasts from all patients patients with biochemical evidence of accumulation of very long chain fatty acids showed normal or near-normal stearic acid beta-oxidation, but were deficient in lignoceric acid beta-oxidation. Residual lignoceric acid beta-oxidation activity varied from approximately 15% in Zellweger syndrome up to 50% in X-linked adrenoleukodystrophy. It is postulated that the accumulation of very long chain fatty acids results from defects in peroxisomal beta-oxidation. In Zellweger's syndrome, and possibly in infantile Refsum's disease, it is probable that this defect is secondary to a primary abnormality affecting the structure and/or function of peroxisomes, while the primary defect in X-linked adrenoleukodystrophy may be confined to a pathway specific for the oxidation of very long chain fatty acids.

Adrenoleukodystrophy↗
PubMed1976

Adrenoleukodystrophy with disease of the eye and optic nerve.

Adrenoleukodystrophy is an X-chromosome-linked recessive disease characterized by primary atrophy of the adrenal glands with or without Addison's disease and low plasma cortisol levels, and a degeneration of white matter of the central nervous system with blindness. In suspected cases of adrenoleukodystrophy an impaired rise in plasma cortisol levels after adrenocorticotrophin stimulation may be diagnostic. With the electron microscope, pathognomonic intracytoplasmic lamellar inclusions have been seen in adrenal cortical cells, peripheral nerve Schwann's cells, testicular interstitial cells, and in macrophages of the brain. Adrenoleukodystrophy appears to be a genetically determined lipid storage disease with an error in membrane sterol metabolism. A 10-year-old boy with adrenoleukodystrophy had visual loss, a prominent early symptom. The ocular abnormality consisted of a disproportionate loss of nerve fibers from the macular region. No intracytoplasmic lamellar inclusions were identified in cells representing macrophages within the optic nerve. They contained myelin debris suggestive of end-stage disease.

Adrenal Gland Diseases↗
PubMed1987

Adrenoleukodystrophy: dietary oleic acid lowers hexacosanoate levels.

Adrenoleukodystrophy (ALD) is an X-linked disorder characterized by demyelination, adrenal insufficiency, and accumulation of saturated very-long-chain fatty acids (VLFA), particularly hexacosanoate (C26:0). We treated 5 patients with adrenoleukodystrophy (3 males and 2 symptomatic female carriers) for 6 months with a diet enriched in oleic acid (C18:1) and moderately restricted in C26:0. Elevated plasma and erythrocyte levels of C26:0 decreased in a time-dependent manner during treatment. Total plasma C26:0 concentration was lowered by 50 +/- 9% (p less than 0.01); it became normal in the female carriers. The total erythrocyte level of C26:0 decreased (44 +/- 5%; p less than 0.001) into the normal range in all patients. Significant decreases were noted in the saturated VLFA composition of plasma and erythrocyte sphingomyelin and erythrocyte phosphatidylcholine during dietary treatment. In general, decreases in saturated VLFA levels were accompanied by increases in monounsaturated VLFA levels, while total VLFA values did not change. This novel approach to the treatment of adrenoleukodystrophy, in which there is an exchange of monounsaturated VLFA for the more toxic saturated VLFA, may prove clinically beneficial in this disorder.

Adrenoleukodystrophy↗
PubMed1985

Cerebro-hepato-renal (Zellweger) syndrome, adrenoleukodystrophy, and Refsum's disease: plasma changes and skin fibroblast phytanic acid oxidase.

Cerebro-hepato-renal (Zellweger) syndrome, adrenoleukodystrophy, and Refsum's disease patients can be divided into at least five distinct groups, according to the nature of their plasma changes and their fibroblast phytanic acid oxidase activities. The biochemical changes in the plasma vary from an increase in a single metabolite or group of structurally related metabolites, such as in X-linked adrenoleukodystrophy (ALD) and classical Refsum's disease, to an increase in a number of structurally distinct metabolites, as in neonatal ALD/Zellweger syndrome, and infantile Refsum's disease. All patients, with the exception of those with the X-linked form of adrenoleukodystrophy are deficient in phytanic acid oxidase activity. The great similarity observed in neonatal adrenoleukodystrophy/Zellweger syndrome and infantile Refsum's disease suggests that the basic biochemical lesion in each may be similar or at least closely related.

Adrenoleukodystrophy↗
PubMed1987

Infantile Refsum disease: an inherited peroxisomal disorder. Comparison with Zellweger syndrome and neonatal adrenoleukodystrophy.

Three patients affected by infantile Refsum disease are described with mental retardation, minor facial dysmorphia, chorioretinopathy, sensorineural hearing deficit, hepatomegaly, failure to thrive and hypocholesterolaemia. Initially, only an accumulation of phytanic acid was thought to be present. More recent findings showed a biochemical profile very similar to that found in classical Zellweger syndrome or neonatal adrenoleukodystrophy. Morphologically typical peroxisomes were absent in the liver. All three disorders are associated with multiple peroxisomal dysfunction. Because of these similarities pertinent clinical data of our three patients are compared with those of reported patients diagnosed as having infantile Refsum disease, neonatal adrenoleukodystrophy or Zellweger syndrome who survived for several years. Attention is drawn to the difference in severity of clinical features, ranging from infantile Refsum's disease to neonatal adrenoleukodystrophy and, finally, to Zellweger syndrome.

Adrenoleukodystrophy↗
PubMed1988

Direct demonstration that the deficient oxidation of very long chain fatty acids in X-linked adrenoleukodystrophy is due to an impaired ability of peroxisomes to activate very long chain fatty acids.

A method was developed to prepare peroxisome-enriched fractions depleted of microsomes and mitochondria from cultured skin fibroblasts. The method consists of differential centrifugation of a postnuclear supernatant followed by density gradient centrifugation on a discontinuous Metrizamide gradient. The activity of hexacosanoyl-CoA synthetase was subsequently measured in postnuclear supernatants and peroxisome-enriched fractions prepared from cultured skin fibroblasts from control subjects and patients with X-linked adrenoleukodystrophy. Whereas the hexacosanoyl-CoA synthetase activity in postnuclear supernatants of X-linked adrenoleukodystrophy fibroblasts was only slightly decreased (77.8 +/- 4.4% of control (n = 15], enzyme activity was found to be much more markedly reduced in peroxisomal fractions isolated from the mutant fibroblasts (19.6 +/- 6.7% of control (n = 5]. This is a direct demonstration that the defect in X-linked adrenoleukodystrophy is at the level of a deficient ability of peroxisomes to activate very long chain fatty acids, as first suggested by Hashmi et al. [Hashmi, M., Stanley, W. and Singh, I. (1986) FEBS Lett. 86, 247-250].

Adrenoleukodystrophy↗
PubMed1989

Adrenoleukodystrophy: a nursing challenge.

Adrenoleukodystrophy has only recently been recognized as a disorder unique to children. Its debilitating sequelae have a profound impact on the physical, psychosocial, and cognitive development of children. Superimposed on coping with the crisis of illness is the stressor of hospitalization, a common experience for children with adrenoleukodystrophy. This article focuses on nursing's contribution to facilitating children's adaptation to the stressors of a progressive disorder, adrenoleukodystrophy, and hospitalization. Utilizing a developmental approach, the psychosocial needs of these children are addressed in a format based on the nursing process.

Adrenoleukodystrophy↗
PubMed1988

A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy).

In the present paper two siblings are presented with clinical manifestations very similar to those of patients affected by neonatal adrenoleukodystrophy. In contrast to neonatal adrenoleukodystrophy patients, hepatic peroxisomes in these siblings were enlarged in size and not decreased in number. Accumulation of very-long-chain fatty acids (VLCFA) was associated with an isolated deficiency of the fatty acyl-CoA oxidase, the enzyme that catalyzes the first step of the peroxisomal beta-oxidation. Plasma levels of di- and trihydroxy-coprostanoic acid, phytanic acid, and pipecolic acid were normal; furthermore, acyl-CoA:dihydroxyacetone phosphate acyltransferase activity in cultured fibroblasts was also found to be normal. The clinical, biochemical, and cytochemical features found in these two siblings are compared with those seen in two other disorders characterized by the absence of a decreased number of hepatic peroxisomes and the presence of VLCFA: (1) pseudo-Zellweger syndrome (deficiency of peroxisomal thiolase activity) and (2) X-linked childhood adrenoleukodystrophy (deficiency of activation of lignoceric acid). Review of the different biochemical defects possible in very-long-chain fatty-acid oxidation reveals different clinical pictures of varying severity, depending on the level at which the biochemical defect occurs.

Acetyl-CoA C-Acetyltransferase↗
PubMed1976

Histochemical characteristics of the striated inclusions of adrenoleukodystrophy.

The straited accumulations in adrenal cortical cells and brain macrophages that are characteristic of adrenoleukodystrophy have been studied histochemically in cryostat sections to seek leads for the biochemical identification of the striated material. It stained pale pink with oil red O and did not stain with the Schultz cholesterol procedure or periodic acid-Schiff technique. By utilizing the birefringence of the accumulations as a marker, it was determined that, unlike natural cholesterol and cholesterol esters, the striated material was resistant to acetone and ethanol extraction. It was readily soluble, however, in nonpolar solvents such as n-hexane and chloroform. These findings indicated that the material was most probably a lipid, and they suggested that sequential extraction of adrenoleukodystrophy adrenal and brain with acetone and then n-hexane could be used to isolate this material in relatively pure form. Based on this lead, biochemical studies have just revealed a fatty acid abnormality in adrenoleukodystrophy which appears to be unique to this genetic disease.

Adrenal Cortex↗