Spondyloepimetaphyseal dysplasia with neurodegeneration associated with AIFM1 mutation - a novel phenotype of the mitochondrial disease.

In 1999, based on a single family, spondyloepimetaphyseal dysplasia (SEMD) with mental retardation (MR) was described as a novel syndrome with probably X-linked recessive inheritance and unknown molecular defect (MIM 300232). Our purpose was to search for the causative defect in the originally described family and in an independently ascertained second family. All patients had slowly progressive neurodegeneration with central and peripheral involvement and identical skeletal dysplasia. Whole exome sequencing performed in two subjects showed a single plausible candidate - the p.Asp237Gly variant in AIFM1 (chr. Xq26.1). The p.Asp237Gly segregated with disease as indicated by linkage analysis [maximum logarithm of odds score (LOD) score at theta 0 for the two families was 3.359]. This variant had not been previously reported and it was predicted to be pathogenic by Polyphen2, SIFT, MutationTaster and Mutation Assessor. AIFM1 encodes mitochondria associated apoptosis-inducing factor. The AIFM1 gene has been linked with COXPD6 encephalomyopathy (MIM 300816), Cowchock syndrome (MIM 310490) and X-linked deafness with neuropathy (DFNX5, MIM 300614), none of which are similar to SEMD-MR. Our results place SEMD as the third instance of a skeletal phenotype associated with a mitochondrial disease (the others being EVEN-PLUS syndrome caused by mutations of HSPA9 and CODAS syndrome due to LONP1 mutations).

Distribution and properties of human intestinal diamine oxidase and its relevance for the histamine catabolism.

High activities of diamine oxidase (EC 1.4.3.6) were measured in the intestinal tract of human subjects and of several mammalian species. The enzyme was localized in the mucosa and was distributed primarily in the cytoplasm; the only exception being the guinea-pig where it was located in the particulate fraction. Despite its instability the enzyme from human colonic mucosa was purified 80-fold. During the purification a soluble monoamine oxidase (EC 1.4.3.4) was separated from diamine oxidase. The pH optima of diamine oxidase for putrescine and histamine were 6.6-7.0 and 6.4-6.6, respectively. Short-chain aliphatic diamines were deaminated with the highest reaction velocity, but histamine and N tau-methylhistamine were also excellent substrates. The Km for putrescine was 8.3 x 10(-5) M, for histamine 1.9 x 10(-5) M and for N tau-methylhistamine 9.7 x 10(-5) M. Typical substrates of monoamine oxidase were not deaminated by the enzyme. Aminoguanidine strongly inhibited human intestinal diamine oxidase (IC50 = 1.1 x 10(-8) M). Because of its properties the intestinal diamine oxidase is considered to play a protective role against histamine in diseases such as ischaemic bowel syndrome, mesenteric infarction and ulcerative colitis.

An evaluation of the TSE MR sequence for time efficient data acquisition in polymer gel dosimetry of applications involving high doses and steep dose gradients.

The use of magnetic resonance imaging as a readout method for polymer gel dosimetry commonly involves long imaging sessions, particularly when high spatial resolution is required in all three dimensions, for the investigation of dose distributions with steep dose gradients and stringent dose delivery specifications. In this work, a volume selective turbo spin echo (TSE) pulse sequence is compared to the established Carr-Purcell-Meiboom-Gill (CPMG) multiecho acquisition with regard to providing accurate dosimetric results in significantly reduced imaging times. Polyethylene glycol diacrylate based (PABIG) gels were irradiated and subsequently scanned to obtain R2 relaxation rate measurements, using a CPMG multiecho sequence and a dual echo TSE utilizing an acceleration (turbo) factor of 64. R2 values, plotted against corresponding Monte Carlo dose calculations, provided calibration data of PABIG gels dose response over a wide dose range. A linear R2 versus dose relationship was demonstrated for both sequences with TSE results presenting reduced dose sensitivity. Although TSE data were found to deviate from linearity at lower doses compared to CPMG data, a relatively wide dynamic dose range of response extending up to approximately 100 Gy was observed for both sequences. The TSE and CPMG sequences were evaluated with a brachytherapy irradiation using a high dose rate 192Ir source and a gamma knife stereotactic radiosurgery irradiation with a single 4 mm collimator helmet shot. Dosimetric results obtained with the TSE and CPMG are shown to compare equally well with the expected dose distributions for these irradiations. The 60-fold scan time reduction achieved with TSE implies that this sequence could prove to be a useful tool for the introduction of polymer gel dosimetry in clinical radiation therapy applications involving high doses and steep dose gradients.

Oxidative deamination of 14C putrescine in mouse tissues in vivo.

Oxidative deamination of 14C putrescine was examined in vivo in mice. Exogenous putrescine is catabolized rapidly; 2.5 min after i.v. putrescine infection, its main oxidative metabolites, namely GABA and an unidentified compound were detected in all tissues tested; inhibition of DAO activity by aminoguanidine strongly suppressed formation of both products.

The importance of human intestinal diamine oxidase in the oxidation of histamine and/or putrescine.

Histamine, naturally methylated histamine and putrescine are good substrates for human intestinal diamine oxidase, N-Methyl-N-formylhydrazine, the constituent of the mashroom poison-gyromitrin is an inhibitor of human intestinal diamine oxidase. Burimamide inhibits more effectively mammalian intestinal diamine oxidases than pea seedling diamine oxidase, beta-aminopropionitrile is a better inhibitor of pea seedling enzyme than mammalian diamine oxidases. This inhibitory differences might be related to preference in histamine or putrescine oxidizing activity of these enzymes.

Rhizomelic spondyloepimetaphyseal dysplasia.

Spondyloepipmetaphyseal dysplasias (SEMDS) are characterized by flattening of the vertebral bodies and epi-metaphyseal involvement of all the tubular bones. We report a 13 year-old boy with a novel variant of SEMD that presents with rhizomelic/mesomelic shortening of the extremities and normal head, hands and feet. Variable metaphyseal involvement and relatively large proximal humeral and knee epiphyses are further distinctive radiographic features in this patient.

[Clinical application of proton magnetic resonance spectroscopy for differential diagnosis of pediatric posterior fossa tumors]. / Zastosowanie Spektroskopii Protonowej Rezonansu Magnetycznego w diagnostyce róznicowej nowotworów tylnego dolu czaszki u dzieci.

We report here on a correlation between proton magnetic resonance spectroscopy (MRS) spectra obtained in children with posterior fossa tumors and tumor histology and grading. Twenty-six children (age 1-16) were investigated before surgery by using single-voxel proton MRS. All examination were performed on a 1.5 T MR scanner by using single-voxel (8 cm3) with PRESS sequence (TR 1600 ms, TE 270 ms, NEX 256). Spectra of N-acetylaspartate (NAA), choline containing compounds (Cho), creatine and phosphocreatine (Cr) and lactate (Lac) were evaluated. Absolute concentrations of the metabolites were measured and their ratios were calculated. Correlation between these and tumor histology and grading were then determined. Concentration of Cho and Lac, and Cho/NAA ratio were the major statistically significant parameters for discrimination between benign (WHO grade I and II) and malignant tumors (WHO grade III and IV), in particular between pilocytic astrocytomas and medulloblastomas. Discrimination between individual histological types within malignant and benign tumor groups was not possible. Proton MRS of pediatric posterior fossa tumors seems to be helpful in prediction of tumor grading and histology. Specific character of the examination requires establishing of the individual standards for every MR scanner.

[Dominant symphalangism and conductive hearing loss]. / Symfalangizm proksymalny i niedosluch przewodzeniowy.

Dominant symphalangism in three generations is presented in this paper. Conductive hearing loss of 14 year old male patient with proximal symphalangism was due to fixation of the stapes.

[Alpha-mannosidosis in two siblings]. / Alfa-mannozydoza u dwojga rodzenstwa.

A rare metabolic disease, alpha-mannosidosis, is described in two siblings. Psychomotoric deficiency, deafness, coarse face and radiological changes in the skeletal system indicated an inherited lysosomal storage disease.

Robinow syndrome: report of two cases and review of the literature.

We report two patients with Robinow syndrome, review the published literature and stress the importance and limitations of radiographic examination in the diagnosis of this disorder, which shows extreme clinical and radiographic variability. The radiographic differential diagnosis of Robinow syndrome is discussed.

Biochemical, physiological and pathophysiological aspects of intestinal diamine oxidase.

Studies were performed on the distribution and properties of intestinal diamine oxidase (DAO) previously called histaminase. DAO activity is high in the gastrointestinal tract of all investigated species. The highest values are in the aboral part of the small intestine: where DAO is localized in the mucosa, predominantly in the top villus region. A high reaction velocity of human intestinal DAO is observed with putrescine, methylhistamine and histamine. H2 receptor antagonists and an agonist (impromidine) inhibit intestinal DAO. The physiological and pathophysiological significance of intestinal DAO in the regulation of histamine and putrescine levels is described, as is the possibility that DAO may act as a growth retardant.

Brachytelephalangic chondrodysplasia punctata.

A case is reported here of a boy with brachytelephalangic chondrodysplasia punctata. This is the first case of this disorder reported in the Australian literature.

Spondylo-epimetaphyseal dysplasia: a new X-linked variant with mental retardation.

UNLABELLED: A new X-linked variant of spondylo-epimetaphyseal dysplasia with distinctive phenotype and severe mental retardation in three boys of one family is reported. The children were normal at birth. After several months of normal development progressive physical disability and slow mental deterioration were observed. Extensive biochemical tests were normal. CONCLUSION: These patients represent a new form of X-linked spondylo-epimetaphyseal dysplasia.

Inhibition of plant and mammalian diamine oxidases by hydrazine and guanidine compounds.

1. Pig kidney and pea seedling diamine oxidases have similar sensitivity to methylhydrazine and phenylhydrazine as inhibitors. 2. Inhibition of pig kidney and pea seedling enzymes by hydrazine and guanidine compounds is time dependent. To reveal full inhibitory potency, methylhydrazine and aminoguanidine need longer preincubation with plant diamine oxidase as compared with mammalian diamine oxidase. 3. Impromidine, a known H2 histamine receptor agonist with guanidine and imidazole structures, and aminoguanidine have higher inhibitory activity towards pig kidney enzyme in comparison with the pea seedling one. 4. Impromidine inhibits pig kidney diamine oxidase in a noncompetitive manner. The Ki value is 6.6 muM. 5. The 24 hr dialysis of rat intestinal diamine oxidase preincubated with phenylhydrazine or impromidine only partially recovered the enzymic activities. 6. Impromidine inhibits mouse intestinal diamine oxidase in vivo.

Inhibition of plant and mammalian diamine oxidase by substrate analogues.

Imidazoles, aliphatic substrate analogues and the natural dipeptides, carnosine and anserine, were investigated as inhibitors of diamine oxidase from the pig kidney, human pregnancy plasma and pea seedlings. Imidazole, methylimidazoles, N-acetylimidazole, histamine and N tau-methylhistamine are relatively potent inhibitors of mammalian diamine oxidase showing no influence on plant enzymes. Anserine and carnosine are inhibitors of pig kidney and pea seedling enzymes. Ki values are 2 microM and 10 microM respectively. Investigated natural derivatives of putrescine and cadaverine have no influence on diamine oxidase of different origin. In conclusion, we present some evidence to suggest that mammalian diamine oxidase, despite a high reaction rate with putrescine, is better adapted to histamine oxidation, whereas for plant enzymes the diamines are preferred substrates.

Diastrophic dysplasia with severe primary kyphosis and 'monkey wrench' appearance of the femora.

The cases of two sisters with severe diastrophic dysplasia who showed some unusual radiographic features (kyphosis secondary to hypoplasia/dysplasia of the lumbar spine and a 'monkey wrench' appearance of the proximal femur) are reported here. Absent patellae were another feature that has not previously been reported in diastrophic dysplasia.

N-methyl-N-formylhydrazine: a toxic and mutagenic inhibitor of the intestinal diamine oxidase.

N-methyl-N-formylhydrazine is the first active intermediate of the poison gyromitrin of the mushroom: false morel. This compound is a non-competitive inhibitor of human intestinal diamine oxidase (ID50 = 1.6 X 10(-5) mol/l). This concentration corresponds to less than 5 g of wet weight of mushroom/l. The diamine oxidases from 5 other sources are inhibited in a similar manner. Semicarbazide and aminoguanidine are 10-respectively 1000-fold more potent inhibitors of the human intestinal diamine oxidase. An involvement of the diamine oxidase inhibitory property of N-methyl-N-formylhydrazine in toxic and mutagenic effects of the substance is considered.

Diamine oxidase in the hen.

In adult hens diamine oxidase (histaminase) activity was found in gastrointestinal tract (with the highest value in ileum), liver and spleen. Intestinal diamine oxidase is predominantly a particle-bound enzyme. In the intestine oxidation of putrescine leads to delta 1-pyrroline formation, in liver both delta 1-pyrroline and gamma-aminobutyric acid are formed. The inhibitor properties of hen intestinal and rat intestinal diamine oxidases are very similar and differ from pea seedling diamine oxidase. The natural dipeptides carnosine and anserine are relatively potent inhibitors of hen intestinal diamine oxidase.

Ceruloplasmin and liver diamine oxidase in guinea pig after industrial emulsifiers application.

Plasma ceruloplasmin and liver diamine oxidase were measured in guinea pigs pretreated with industrial emulsifiers (long chain aliphatic amines combined with ethylene oxides). Emulsifiers produced biphasic changes in ceruloplasmin activity. An increase observed the 1st and 3rd day was followed by a drop at the 7th day. Diamine oxidase was diminished markedly at 1st day. The inflammation of liver followed by its impairment produced by industrial emulsifiers is discussed as a cause of these metabolic changes.