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B T Poll-The

Publications and source records attributed to B T Poll-The.

At least 109 records · Page 6Linked to original sources
PubMed1989

Phytanic acid alpha-oxidation and complementation analysis of classical Refsum and peroxisomal disorders.

We have measured the production of 14CO2 from exogenous [1-14C] phytanic acid in fibroblast monolayers from patients with classical Refsum's disease and peroxisomal disorders. Activities in the different disorders were (percentage of control): classical Refsum's disease (5%), isolated peroxisomal acyl-CoA oxidase deficiency (75%), Zellweger syndrome (4%), neonatal adrenoleukodystrophy (5%), and rhizomelic chondrodysplasia punctate (3%). Absence of complementation was demonstrated between Zellweger syndrome and infantile Refsum's disease lines after polyethylene glycol fusion, with decreases of average activity of 11% relative to unfused cell mixtures. Classical Refsum's disease, rhizomelic chondrodysplasia punctata, and neonatal adrenoleukodystrophy lines all complemented one another, and Zellweger syndrome or infantile Refsum's disease lines, with average activity increases of 522%-772%. No intragenic complementation was observed within either group. Four complementation groups were detected suggesting that at least four genes are involved in phytanic acid alpha-oxidation: one gene for the enzyme phytanic acid alpha-hydroxylase (probably mitochondrial); one gene for a regulatory factor for the expression of phytanic acid alpha-decarboxylation activity and two membrane-bound peroxisomal enzymes involved in the synthesis of plasmalogens; two genes for the assembly of functional peroxisomes and/or import of proteins into peroxisomes.

Adrenoleukodystrophy↗
PubMed1989

[Neonatal adrenoleukodystrophy. Apropos of 3 cases in siblings].

Neonatal adrenoleukodystrophy is a recently individualized disease manifested by very early onset of neurologic deterioration. Progression of the disease is rapid and there is no effective therapy. Differences with X-linked adrenoleukodystrophy include genetic inheritance, which is autosomal recessive, a more severe prognosis, and presence of multiple peroxisome enzyme deficiencies that justify classification alongside the Zellweger syndrome among the peroxisome disorders. We report three cases in siblings and describe the main clinical and biochemical features.

Adrenoleukodystrophy↗
PubMed1988

de Toni-Fanconi-Debré syndrome with Leigh syndrome revealing severe muscle cytochrome c oxidase deficiency.

We describe a patient with severe muscle cytochrome c oxidase deficiency who had de Toni-Fanconi-Debré syndrome and acute neurologic deterioration resembling Leigh syndrome, without clear evidence of muscle abnormality. Metabolic investigations revealed elevated cerebrospinal fluid lactate values contrasting with normal blood lactate, and high 3-hydroxybutyrate/acetoacetate ratio with normal lactate/pyruvate ratio. This case emphasizes the importance of performing metabolic and biochemical investigations in every patient with Leigh syndrome, even in the absence of hyperlactatemia or myopathy.

Brain Diseases, Metabolic↗
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↗
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↗
PubMed1987

Bile acids in peroxisomal disorders.

We examined serum bile acids in patients with different peroxisomal disorders. Patients with Zellweger syndrome (n = 23), infantile form of Refsum disease (n = 6) and neonatal adrenoleukodystrophy (n = 4) consistently had increased levels of bile acid precursors. Patients with X-linked adrenoleukodystrophy, (n = 5) classical Refsum disease (n = 3), hyperpipecolic acidaemia (n = 4) and rhizomelic chondrodysplasia punctata (n = 9) did not have increased bile acid precursor levels. Total serum bile acids (41 micrograms ml-1) and the percentage of bile acid precursors (80%) were highest in typical Zellweger patients who died young. Long-living Zellweger patients, neonatal adrenoleukodystrophy patients and infantile Refsum disease patients had, on average, less cholestasis and a lower percentage of bile acid precursors. We also observed that total serum bile acids and the percentage of bile acid precursors decreased with age in long-living Zellweger patients. Screening for bile acid precursors, combined with very long chain fatty acids analysis is, in our experience, an easy and reliable first-line approach to the detection of peroxisomal disorders.

Adrenoleukodystrophy↗
PubMed1986

Hepatic peroxisomes are deficient in infantile refsum disease: a cytochemical study of 4 cases.

We examined liver biopsies from 4 patients with the infantile form of Refsum disease. No peroxisomes were visualized by light microscopy after cytochemical staining for catalase, a marker enzyme for this organelle. Absence of peroxisomes was confirmed by electron microscopy in 3 patients; in the 4th patient we observed organelles of peculiar size and structure and with minimal catalase activity. Light microscopy also showed birefringent macrophages containing P.A.S.-positive material; they were abundant in the 3 older children, and rare in the youngest (8 months). Peroxisomes and birefringent macrophages were absent in 2 patients with the cerebrohepatorenal syndrome of Zellweger. The simultaneous presence of these unique light microscopical characteristics may be of diagnostic value.

Birefringence↗
PubMed1986

Infantile Refsum's disease: biochemical findings suggesting multiple peroxisomal dysfunction.

Infantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth and psychomotor development. An elevated plasma phytanic acid concentration and a deficient phytanic acid oxidase activity in fibroblasts were found with an accumulation of very long chain fatty acids in plasma and fibroblasts. There were elevated pipecolic acid levels in plasma, urine and CSF, and abnormal bile acid metabolites in plasma. Deficient activity of acylCoA: dihydroxyacetone phosphate acyl transferase was found in thrombocytes and fibroblasts of these patients as well as an impaired de novo plasmalogen biosynthesis in fibroblasts. These biochemical abnormalities, previously described in the Zellweger syndrome, suggest multiple peroxisomal dysfunction in our patients.

Acyltransferases↗
PubMed1986

Prenatal diagnosis of Zellweger syndrome and related disorders: impaired degradation of phytanic acid.

Normal amniocytes and chorionic villous cells in culture are able to produce 14CO2 from exogenous [1-14C] phytanic acid. In contrast, cells from four fetuses at risk for the cerebro-hepato-renal (Zellweger) syndrome and related disorders showed a greatly reduced activity, indicating a block in oxidation of the fatty acid. Our data confirm that phytanic acid oxidase activity measurement can be used for the prenatal assessment of this group of disorders.

Adult↗
PubMed1985

Neurological findings in triosephosphate isomerase deficiency.

Two siblings with hemolytic anemia caused by triosephosphate isomerase deficiency developed a progressive neurological syndrome featuring dystonic movements, tremor, pyramidal tract signs, and evidence of spinal motor neuron involvement. Intelligence was unaffected. The findings in these patients and in 14 previously published cases indicate that neurological manifestations are an integral part of the disorder and suggest that specific structures in the basal ganglia, brainstem, and spinal cord bear the brunt of the pathological process, which does not affect the cerebral cortex.

Anemia, Hemolytic↗
PubMed1985

Pseudomonoventricle due to a malformation of the septum pellucidum.

Three children with complete absence of the frontal horns of the lateral ventricles and a single midline cavity on CT scan are reported. Two patients presented with adipsia, persistent serum hyperosmolarity and partial central diabetes insipidus. Another presented with congenital hemiplegia. The CT appearance was different from that of the known causes of monoventricle and was attributable to a malformation of the septum pellucidum, first described neuropathologically by Gross and Kaltenbäck (1957) who termed it frontal pseudomonoventricle.

Cerebral Ventricles↗
PubMedDate not supplied

Phenylketonuria in The Netherlands: 93% of the mutations are detected by single-strand conformation analysis.

Single-strand conformational analysis was used to screen for genetic defects in all thirteen exons of the phenylalanine hydroxylase gene (PAH) in phenylketonuria and hyperphenylalaninemia patients in the Netherlands. Exons that showed a bandshift were sequenced directly. In this way, we were able to identify 93% of the PAH mutations in a panel of 34 patients. Twenty-one different mutations were found: 4 of these gene aberrations are novel.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

Cytoplasmic catalase and ghostlike peroxisomes in the liver from a child with atypical chondrodysplasia punctata.

In the liver biopsy from an 8.5-year-old girl with the biochemical characteristics of rhizomelic chondrodysplasia punctata (RCDP), but with normal limbs, normal catalase-containing peroxisomes were absent. Light microscopy after diaminobenzidine staining for catalase activity (the peroxisomal marker enzyme) and immunostaining against catalase protein indicated a cytosolic localization of the enzyme. By electron microscopy, rare and extremely large, irregularly shaped vesicles were found in the parenchymal cells. The three peroxisomal beta-oxidation enzymes (acyl-CoA oxidase, bi(tri)functional enzyme, and 3-ketoacyl-CoA thiolase) and alanine-glyoxylate aminotransferase were immunolocalized in these organelles. However, a weak to negative label was obtained after staining against catalase. Diaminobenzidine staining demonstrated a minimal catalase reaction product in some vesicles only. Morphometry revealed a corrected mean d-circle of 1.44 microns and a maximum d-circle of 2.767 microns (controls: 0.635 microns and 1.027 microns, respectively). Numerical, volume, and surface densities were reduced to 3%, 41%, and 17% of control values, respectively. The large size, irregular shape, and rarity of the organelles are morphologic features of peroxisomal "ghosts." It seems that in this patient, apart from the known peroxisomal defects in RCDP, catalase incorporation into the peroxisomes is impaired together with a normal proliferation (division) of the organelles. In the cultured skin fibroblasts from the patient, however, immuno-electron microscopy showed normal catalase-containing peroxisomes in apparently normal numbers.

Catalase↗