1/15. Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution.We describe an 18-year-old patient with psychomotor retardation and abnormally short metatarsi and metacarpals but no other signs of classic refsum disease. Molecular analysis of the phytanoyl-coenzyme a hydroxylase gene revealed a homozygous deletion causing a frameshift. Surprisingly, L-pipecolic acid was elevated in plasma, and microscopy of the liver showed a reduced number of peroxisomes per cell and a larger average peroxisome size. These abnormal peroxisomes lacked catalase as did peroxisomes in fibroblasts of this patient. Such generalized peroxisomal abnormalities are not present in classic refsum disease.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
2/15. Refsum's disease: electron microscopy of an iris biopsy.Refsum's disease (phytanic acid storage disease) results in an accumulation of lipid as a result of an absence of mitochondrial hydroxylation of phytanic acid. We describe a previously unrecorded electron microscopic study of lipid deposition in the iris pigment epithelium of a patient with Refsum's disease, and lipid was present in other sites within the iris.- - - - - - - - - - ranking = 2731.1619747686keywords = storage disease, storage (Clic here for more details about this article) |
3/15. Infantile phytanic acid storage disease, a disorder of peroxisome biogenesis: a case report.The infantile and classic forms of phytanic acid storage disease belong to the newly recognized group of peroxisomal disorders. In this paper we report the full clinical, morphological and biochemical results in a patient with infantile phytanic acid storage disease. The results indicate a generalized loss of peroxisomal functions due to a deficiency of peroxisomes as demonstrated in hepatocytes and cultured skin fibroblasts.- - - - - - - - - - ranking = 16386.971848612keywords = storage disease, storage (Clic here for more details about this article) |
4/15. Dysmorphic syndrome with phytanic acid oxidase deficiency, abnormal very long chain fatty acids, and pipecolic acidemia: studies in four children.We describe a relatively new syndrome in four children with characteristic facial dysmorphism, sensorineural hearing loss, severe visual impairment with retinitis pigmentosa, hypotonia, hepatomegaly, and severe developmental delay. Two patients had intracranial hemorrhage secondary to a vitamin k-responsive clotting defect; both had steatorrhea. liver biopsy specimens in two children showed an accentuated lobular architecture with prominent fibrous bands in the portal area. In one, the ultrastructure showed accumulation of abnormal substances and occasional trilaminar structures in hepatocytes and other cells. All four patients had elevated serum phytanic acid concentrations (0.3 to 2.7 mg/dl, normal less than 0.2 mg/dl) and deficient fibroblast phytanic acid oxidase activity (0.1 to 6.7 pmol/mg protein/hr, normal 23 to 87 pmol/mg protein/hr). serum pipecolic acid was 7 to 55 times normal, and the ratio of C26/C22 very long chain fatty acids was increased (0.10 to 0.22; normal less than 0.03). This characteristic syndrome has been described in several children and called infantile refsum disease or phytanic acid storage disease. Its relationship to neonatal adrenoleukodystrophy, hyperpipecolic acidemia, and zellweger syndrome is discussed.- - - - - - - - - - ranking = 2731.1619747686keywords = storage disease, storage (Clic here for more details about this article) |
5/15. peroxisomes in infantile phytanic acid storage disease: a cytochemical study of skin fibroblasts.Cultured skin fibroblasts from six patients demonstrating clinical signs and biochemical characteristics of infantile phytanic acid storage disease (IPSD) were examined by electron microscopy, using cytochemical procedures for the demonstration of peroxisomal catalase activity. In four of the six fibroblast cell lines peroxisomes strongly reactive for catalase were present in numbers similar to those found in normal fibroblasts. liver biopsy tissue from one of these patients showed no typical hepatic peroxisomes, but did show small, marginally reactive bodies. In two other IPSD fibroblast cell lines peroxisomes with appreciable cytochemical reactivity were rare or absent. It seems, therefore, that infantile phytanic acid storage disease is heterogeneous with respect to the presence of cytochemically recognizable peroxisomes, at least in the cases studied here. Furthermore, peroxisomes may be markedly affected in one cell type - liver - and yet not affected in another - skin fibroblasts - within a single individual.- - - - - - - - - - ranking = 16386.971848612keywords = storage disease, storage (Clic here for more details about this article) |
6/15. Infantile Refsum's disease: a peroxisomal storage disorder?An 18-month-old infant presented with a history of arrest of neurological development from the age of eight months, with progressive ataxia, deafness, retinitis pigmentosa and hepatomegaly. Biochemical investigations revealed an elevated plasma phytanic acid level and deficiency of phytanic acid oxidase in skin fibroblasts. Histopathological findings in a liver biopsy were similar to those reported in infantile phytanic acid storage disease. Unexpected findings were the presence of elevated levels of plasma pipecolic acid, and elevated plasma long-chain fatty acid ratios, biochemical findings previously considered to be diagnostic of Zellweger's hepato-cerebro-renal syndrome, and of adrenoleucodystrophy, respectively. Recent biochemical evidence suggests that this patient, and other similar cases that have recently come to our attention, may have a fundamental defect in the peroxisomal enzyme system.- - - - - - - - - - ranking = 3435.1198682079keywords = storage disease, storage, enzyme (Clic here for more details about this article) |
7/15. Peroxisomal very long-chain fatty acid beta-oxidation in human skin fibroblasts: activity in zellweger syndrome and other peroxisomal disorders.Since very long-chain fatty acids with a chain length of 24 carbons or more are known to accumulate in tissues and body fluids from patients with the cerebrohepato-renal (Zellweger) syndrome, infantile refsum disease, neonatal adrenoleukodystrophy and X-linked adrenoleukodystrophy, we studied very long-chain fatty acid oxidation in cultured skin fibroblasts from these patients. In this paper, we report that in accordance with earlier results the first step in the beta-oxidation of the very long-chain fatty acid lignoceric acid (C24:0) primarily occurs in peroxisomes in control human skin fibroblasts. Furthermore, it was found that peroxisomal lignoceric acid beta-oxidation was strongly deficient in fibroblasts from patients with zellweger syndrome, infantile Refsum disease, neonatal and X-linked adrenoleukodystrophy, which explains for the accumulation of very long-chain fatty acids in all four disease entities. In zellweger syndrome, infantile refsum disease and neonatal adrenoleukodystrophy the impairment in peroxisomal very long-chain fatty acid beta-oxidation is probably caused by a strong deficiency of all peroxisomal beta-oxidation enzyme proteins due to a deficiency of peroxisomes.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
8/15. Treatment of infantile phytanic acid storage disease: clinical, biochemical and ultrastructural findings in two children treated for 2 years.Two patients with infantile phytanic acid storage disease (infantile refsum disease), one of whom showed the presence of morphologically normal peroxisomes in a liver biopsy, were treated with a low phytanic acid diet for more than 2 years and the effects of treatment on certain clinical, biochemical and ultrastructural parameters were examined. Both patients showed evidence of either an improvement or stabilisation in their clinical condition. plasma phytanic acid levels decreased to near normal values in approximately 6 weeks after the introduction of the diet; plasma pipecolic acid also declined markedly but the decrease was not so rapid and its level remained abnormal. C26:C22 fatty acid ratios decreased very slowly and even after 2 years the values remained grossly abnormal. Despite the marked reduction of phytanic acid in the liver, there was an increase in the C26:C22 fatty acid ratios and this appeared to be paralleled by an increase in inclusion bodies. Our data suggest that some patients with the infantile form of refsum disease may show some clinical benefit from dietary management and this is reflected biochemically by decreases in the plasma levels of phytanic acid and pipecolic acid.- - - - - - - - - - ranking = 13655.809873843keywords = storage disease, storage (Clic here for more details about this article) |
9/15. Infantile phytanic acid storage disease, a possible variant of Refsum's disease: three cases, including ultrastructural studies of the liver.Three cases of phytanic acid storage disease with symptoms during the first months of life are reported. hepatomegaly, facial dysmorphia, growth and/or mental retardation and osteopenia were observed in addition to retinitis pigmentosa and neurosensory deafness. The presence of phytanic acid in serum (160-320 mumol/1 (50-100 micrograms/ml)) was accompanied by hypocholesterolaemia. Electron microscopy showed that a storage material had accumulated in mesenchymal and parenchymal liver cells. Lamellar structures were seen in hepatocytes and other storing cells. These inclusions resembled the structures found in plant chloroplasts containing phytol. Some of the clinical and biological data obtained were consistent with Refsum's disease. However, other characteristics such as mental retardation, hepatomegaly, osteopenia, hypocholesterolaemia and hypoalphalipoproteinaemia, as well as the ultrastructural findings in the liver, suggested that our patients' illness was either a phytanic acid storage disease different from the classical form of Refsum's disease, or a more severe early symptomatic form of Refsum's disease. early diagnosis by phytanic acid assay and electron microscopic liver examination calls for prescription of a low phytanate diet in the hope of improving the child's condition.- - - - - - - - - - ranking = 16562.711321972keywords = storage disease, storage (Clic here for more details about this article) |
10/15. Ophthalmic manifestations of infantile phytanic acid storage disease.Two patients had infantile phytanic acid storage disease. Patient 1 had nystagmus from early infancy, epicanthal folds, esotropia, and a pigmentary retinopathy. The second case had similar manifestations; however, no nystagmus was present. Both patients were hypotonic as infants, had a severe hearing impairment, and were moderately severely developmentally delayed. serum phytanic acid levels in both cases were clearly elevated. The fundus and fluorescein angiogram showed macular and diffuse retinal pigment epithelial defects, vascular attenuation, and pigmentary dispersion. The electroretinogram demonstrated severely subnormal rod- and cone-mediated responses, with greater involvement evident for responses generated by middle and inner retinal neurons compared with responses mediated by photoreceptors. The ophthalmologist may be the first to recognize the characteristic features of this disorder. early diagnosis may be important because this disorder may be ameliorated by dietary restriction of phytanic acid.- - - - - - - - - - ranking = 13655.809873843keywords = storage disease, storage (Clic here for more details about this article) |
| | Next -> |