Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinitis pigmentosa (RP) is the most common form of retinal dystrophy. It is featured by a great clinical and genetic heterogeneity. Different patterns of inheritance exist, such as autosomal dominant and recessive, X-linked and digenic. RP25, a locus for autosomal recessive retinitis pigmentosa (arRP), the most frequently inherited form of RP, was mapped to chromosome 6q between D6S257 and D6S1644 microsatellite markers. ELOVL5, SMAP1 and GLULD1 were selected on the basis of their location, tissue expression and/or function. ELOVL5 is implicated in the elongation of long chain fatty acids, including docosahexanoic acid (DHA), which constitutes 50% of the fatty acids of the outer segment of the photoreceptor. SMAP1 (stromal membrane associated protein 1) was found to be located within RP25 locus and is expressed in retina. GLULD1, glutamate-ammonia ligase (glutamine synthase) domain containing 1, plays a key role in the uptake and metabolism of glutamate in the retina. The absence of pathogenic mutations after molecular analysis argues against the implication of ELOVL5, SMAP1 and GLULD1 in the development of RP25 phenotype. Nevertheless, we could not rule them out as good candidates for other retinal degeneration mapping to the same chromosomal region.
 ...
PMID:Mutation screening of three candidate genes, ELOVL5, SMAP1 and GLULD1 in autosomal recessive retinitis pigmentosa. 1627 1

We have studied a male patient with significant developmental delay, growth failure, hypotonia, girdle weakness, microcephaly, and multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed cytogenetic and molecular analyses revealed three de novo X chromosome aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome aberrations in the patient include: a pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes; and an interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase long chain family member 4 (ACSL4). These findings suggest that the disruption of DMD and the absence of ACSL4 in the patient are responsible for neuromuscular disease and cognitive impairment.
 ...
PMID:Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies. 1627 8

Adrenoleukodystrophy (ALD) and its adult variant adrenomyeloneuropathy (AMN) are X-linked diseases associated with a deficiency in the peroxisomal degradation of saturated very long chain fatty acids (VLCFA) resulting in an accumulation of VLCFA in the central and peripheral myelin, the adrenal cortex and the testis. Adrenal insufficiency with clinical hypocortisolism occurs in approximately two thirds of the patients with AMN. We studied the circulating adrenal hormones 17alpha-hydroxyprogesterone (17alpha-OHP), androstenedione and dehydroepiandrosterone sulphate (DHEAS) in 63 male AMN patients (age 17-65 years) and the DHEAS serum levels in 95 healthy male controls (age 30-65 years). 34 of the patients presented with the phenotype of only spinal cord and peripheral nerve disability without hypocortisolism, 29 of the patients presented with the phenotype of either additional hypocortisolism or Addison's syndrome only. Normal 17alpha-OHP concentrations were found in all patients with no significant difference between patients without and with hypocortisolism (6.07 +/- 0.61 nmol/l and 4.76 +/- 0.37 nmol/l). Androstenedione concentration was significantly (p < 0.01) lower in patients with hypocortisolism (2.99 +/- 0.65 pmol/l versus 5.71 +/- 0.68 pmol/l). As serum levels of DHEAS are agedependent we divided the two groups into two subgroups each (subgroup one: age 17-40 years, subgroup two: age 41-65 years). The DHEAS concentration of patients without and with hypocortisolism was significantly (p < 0.01) lower in both subgroups (1. 4.35 +/- 0.84 micromol/l, n = 15, 2. 15 +/- 0.28 micromol/l, n = 19; 1. 1.90 +/- 0.57 micromol/, n = 21, 2. 0.96 +/- 0.29 micromol/l, n = 8) compared to controls (1. 9.0 +/- 0.96 micromol/l; 2. 5.21 +/- 0.25 micromol/l). In conclusion, androstenedione and DHEAS serum concentrations are subnormal in all AMN patients and may therefore serve as sensitive markers of the adrenal function in adrenomyeloneuropathy.
 ...
PMID:Adrenal steroids in adrenomyeloneuropathy. Dehydroepiandrosterone sulfate, androstenedione and 17alpha-hydroxyprogesterone. 1636 29

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.
 ...
PMID:Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy. 1753 76

In the report "Peroxisomal defects in neonatal-onset and X-linked adrenoleukodystrophies" by S. Goldfischer et al. (4 Jan., p. 67), the first sentence of the abstract should have read: "Accumulation of very long chain fatty acids in X-linked and neonatal forms of adrenoleukodystrophy (ALD) appears to be a consequence of deficient oxidation of very long chain fatty acids, a function that has been attributed to peroxisomes."
 ...
PMID:Erratum. 1779 10

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.
 ...
PMID:Clinical profile of adrenoleukodysrophy. 1990 37

Neonatal adrenoleukodystrophy constitutes a distinct genetic disorder of autosomal recessive inheritance, and is distinguishable from the cerebro-hepato-renal syndrome of Zellweger and X-linked juvenile adrenoleukodystrophy, although all three conditions store very long chain fatty acids. Abnormal clinical features in neonatal adrenoleukodystrophy are generally present at birth, and include muscle hypotonia, severe psychomotor retardation, and failure to thrive. These infants are generally blind and deaf, with seizures developing during their first few weeks. A retinopathic "leopard spot" is common, and should help identify this disorder. The brains of four infants who died of neonatal adrenoleukodystrophy were biochemically analyzed for complex lipids, including cholesterol, cholesterol esters, total phospholipids, total galactolipids, and gangliosides. Additional analyses included the separation and identification of very long chain fatty acids and various forms of brain plasmalogen. Analyses of brains with neonatal adrenoleukodystrophy revealed the chemical identification of at least two stored lipid products. Very long chain fatty acids are present, especially in cholesterol esters, and vinyl ether ethanolamine plasmalogens are markedly elevated. The storage of vinyl ether plasmalogen in brains of infants dying of neonatal adrenoleukodystrophy clearly distinguishes them from those with cerebro-hepato-renal syndrome of Zellweger, which fail to synthesize plasmalogens.
 ...
PMID:Neonatal adrenoleukodystrophy: a clinical, pathologic, and biochemical study. 2304 13

X-linked adrenoleukodistrophy is a severe neurodegenerative disorder with impaired very long chain fatty acid metabolism. The disease associated ABCD1 gene encodes a peroxisomal membrane protein which belongs to the superfamily of ATP-binding cassette transporters. We investigated eight male X-ALD patients diagnosed among 142 suspected patients referred for investigation. Plasma levels of very long chain fatty acids were measured at our laboratory using capillary gas chromatography. Eight cases of childhood X-ALD were diagnosed. This is the first published series of Serbian patients with X-ALD. In addition, diagnosis identifies carriers, which could be benefit for genetic counselling and prenatal diagnosis.
 ...
PMID:X-linked adreno leukodistrophy: Profiles of very long chain fatty acids in plasma and fibroblasts in eigth Serbian patients. 2310 97

Adrenoleukodystrophy (ALD) is a rare X-linked inherited leukodystrophy with a reduced capacity for degradation of very long chain fatty acids (VLCFAs). The intracellular accumulation of VLCFA leads to demyelination in the central nervous system (CNS) and cell destruction in the adrenal glands. ALD primarily affects males; however, females may develop milder symptoms that may be difficult to recognize. The present report describes a 35-year-old female who experienced a feeling of heaviness in the upper and lower limbs, pain in both knees, and difficulty climbing stairs, running, and jumping. Clinical examination revealed decreased sensitivity in the feet, particularly to touch. Deep tendon reflexes in the lower limbs were brisk, and Babinski's sign was present bilaterally. Multiple sclerosis (MS) was excluded, and all clinical and biochemical tests were normal. After two years of progressing symptoms, the patient was reevaluated and plasma levels of VLCFA were found to be elevated. Seven years prior to this finding, the patient had been found to be heterozygous for the missense mutation c.1679C> T, p.Pro560Leu on the ABCD1 gene (ATP-Binding Cassette subfamily D1). In conclusion, the patient's symptoms could be attributed to ALD. The present case underlines the importance of reevaluating family history in women presenting with vague neurological symptoms.
...
PMID:Clinical manifest x-linked recessive adrenoleukodystrophy in a female. 2386 71

X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disorder, in which accumulation of very long chain fatty acids (VLCFAs) results in damage to the central nervous system. As the disease is X-linked, males are affected severely, but female carriers may also present with neurological symptoms. We report the case of a young adult female, who presented with episodic sensorimotor symptoms. Although she was a heterozygous female carrier of X-ALD, subsequent investigations confirmed a diagnosis of multiple sclerosis (MS). To the best of our knowledge, this is the first reported case of a female X-ALD carrier in which the clinical features were more consistent with co-existent MS than ALD-related pathology. The case serves as a reminder that alternative, more common diagnoses should also be considered in carriers of rare neurological syndromes.
...
PMID:Multiple sclerosis in an adrenoleukodystrophy carrier. 2476 66


<< Previous 1 2 3 4 5 Next >>