Screening for tetrahydrobiopterin deficiencies using dried blood spots on filter paper

Tetrahydrobiopterin (BH4) deficiency among newborns with hyperphenylalaninemia must be rapidly diagnosed and distinguished from classical phenylketonuria (PKU) to initiate immediately specific treatment and to prevent irreversible neurological damage. The characteristic pattern of urinary pterins makes it possible to differentiate between PKU and BH4 deficiencies, and to identify different variants of BH4 deficiency. However, collection, storage, and shipment of urine samples for pterin analysis is cumbersome. A method for the measurement of different pterins (neopterin, biopterin, and pterin) in blood collected on filter paper was developed as a potential alternative to the screening for BH4 deficiencies in urine and for the monitoring of BH4 pharmacokinetics. Pterins pattern in blood spots was comparable with those in plasma and urine. We thus established reference values for pterins in blood spots in patients with hyperphenylalaninemia and identified new patients with GTP cyclohydrolase I deficiency, 6-pyruvoyl-tetrahydropterin synthase deficiency, and dihydropteridine reductase deficiency using dried blood spots on filter paper.     

Sarcomas: rare primary malignant tumors of the thorax

In this article, it is aimed to review the radiological signs of unusual primary malignant tumors of the thorax. Radiological studies of 11 patients with histologic diagnosis of thoracic sarcomas were interpreted retrospectively. Tumors originated from the chest wall (n=3), mediastinum (n=4), and pulmonary parenchyma (n=4). Histopathologic diagnoses were fibrosarcoma (n=1), alveolar rhabdomyosarcoma (n=1), malignant hemangiopericytoma (n=1), malignant fibrous histiocytoma (n=2), pulmonary vein leiomyosarcoma (n=1), pulmonary artery sarcoma (n=2), pleuropulmonary blastoma (n=1), and chondrosarcoma (n=2). In order to evaluate thoracic sarcomas, cross-sectional methods such as CT and MRI can be useful in demonstrating the origin of the mass, relationship with and involvement of adjacent structures. They present as masses and, unfortunately, radiological findings are not sufficient for specific diagnosis.     

Biotinidase deficiency: novel mutations and their biochemical and clinical correlates

Biotinidase deficiency is a defect in the recycling of the vitamin biotin. Biotin supplementation can markedly improve the neurological and cutaneous symptoms of affected children and prevent symptoms in children identified by newborn screening or treated since birth. We have determined thirteen novel mutations in children with the disorder. Two nonsense mutations, eight single missense mutations, three allelic double missense mutations, and two are polymorphisms were identified in the biotinidase gene (BTD). One of the missense mutations, c.734G>A (p. C245Y), is the first to be reported that alters the cysteine in the putative location crucial for ester formation and binding of the biotinyl-moiety in the active site of the enzyme. These mutations add to the growing list of mutations that are helping to delineate structure/function relationships of the enzyme.     

Late recurrence of sigmoid carcinoma mimicking primary vulvar cancer: case report and review of the literature

Objective

To demonstrate a unique case report about late and isolated vulvar metastasis of sigmoid adeno-carcinoma with review of the literature.

Material-method

57 year old postmenopausal patient with prior sigmoid colon cancer history was admitted with isolated vulvar mass. Immunohistochemistry (IHC) and KRAS gen mutation analysis following surgery were performed to discriminate the metastasis from a vulvar primary malignancy. Further imaging techniques were also performed to exclude additional tumours.

Results

Immunohistochemistry (IHC) and KRAS gene mutation analysis revealed isolated metastasis of the colonic adeno-carcinoma in the vulva.

Conclusion

Isolated and late occurring vulvar metastasis of colonic origin is very unusual. Careful evaluation and IHC is useful for such cases.     

Corticospinal tract involvement in a patient with 3-HMG coenzyme A lyase deficiency

3-Hydroxy-3-methylglutaryl coenzyme A lyase deficiency, an inborn error of ketone body synthesis and leucine degradation, is a rare disorder. There are few reports demonstrating clinical and neuroradiologic findings of this condition. This report describes a 3.5-year-old previously healthy male who was admitted with complex partial seizures and was diagnosed as having 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency. The patient's previous medical history was unremarkable. His development and neurologic examination were normal. Cranial magnetic resonance imaging indicated prominent corticospinal tract and pontine involvement with focal cerebral white matter changes which have not been described in the literature before.     

Treatment of Lyme neuroborreliosis with plasmapheresis

Lyme disease is a rare tick‐borne multisystemic infection caused by Borrelia burgdorferi. Different neurological conditions were reported in the disease. In this article, we present a 15‐year‐old patient hospitalized with ataxia who was diagnosed with Lyme neuroborreliosis. Intravenous immunoglobulin and ceftriaxone treatment was applied to the patient for 4 weeks. However, ataxia did not recover, upper and lower muscle weakness developed, and deep tendon reflexes diminished during follow‐up. The patient was diagnosed with Guillain–Barre syndrome arising from B. burgdorferi. Second dose of intravenous immunoglobulin treatment was started for 5 days but the patient didn't recover. Therefore administration of plasmapheresis was decided. All symptoms relieved following the plasmapheresis. The effect of plasmapheresis in pediatric neuroborreliosis has not been documented before. This study highlights that plasmapheresis could be a useful alternative for pediatric neuroborreliosis cases. J. Clin. Apheresis 31:476–478, 2016. © 2015 Wiley Periodicals, Inc.     

A case of primary spinal intramedullary lymphoma

A 41-year-old male presented to our clinic with a 1-month history of left hemiparesis. He had marked left arm weakness. The diagnostic work-up revealed an intramedullary mass at spinal level C2-4. Laminectomies were performed at C2-3-4 and the tumor was subtotally resected. Histological examination identified the mass as a non-Hodgkin's diffuse B-cell lymphoma. The patient was treated with corticosteroids, chemotherapy, and adjuvant radiotherapy. The residual tumor tissue had completely disappeared by 6 months of follow-up; however, the patient presented with intraventricular metastasis at 11 months postsurgery.     

Tissue factor pathway inhibitor attenuates procoagulant activity and upregulation of tissue factor at the site of balloon-induced arterial injury in pigs.

Intravenous infusion of recombinant tissue factor pathway inhibitor (rTFPI) for 24 hours decreases neointimal thickening and luminal stenosis 1 month after balloon-induced injury to the carotid arteries in minipigs. This study was designed to determine whether the effect of rTFPI is accounted for by early decreases in procoagulant activity and thrombosis on the injured vessel wall. Vascular injury was induced by balloon hyperinflations in both carotid arteries of anesthetized pigs given no anticoagulant as a control (n=16), an intravenous infusion for 24 hours of rTFPI (0.5 mg/kg bolus and 25 microg. kg(-1). min(-1), n=14), or an intravenous infusion of unfractionated heparin (100 U. kg(-1). h(-1), n=19). Accumulation of radiolabeled autologous platelets was markedly decreased over 24 hours on injured arteries from animals given rTFPI (0.6x10(6)/cm(2)) compared with controls (2.5x10(6)/cm(2), P=0.0004). Deposition of radiolabeled fibrin was also decreased in rTFPI-treated animals (269+/-266 microg/cm(2)) compared with controls (2389+/-1673 microg/cm(2), P=0.04). Similar effects were observed with heparin. However, factor Xa activity, assayed after 24 hours by incubation of the injured arterial segments with the chromogenic substrate S-2222, was decreased more markedly on arteries from rTFPI-treated animals (0.14+/-0.13 OD) than those from heparin-treated animals (0.29+/-0.18 OD) compared with controls (0. 47+/-0.24 OD, P=0.0007). In addition, arteries from rTFPI-treated animals showed a 4-fold lower induction of tissue factor protein compared with controls (P=0.0002). Attenuation of procoagulant activity and tissue factor-mediated thrombin generation in response to injury may account for the promising results with rTFPI in the porcine angioplasty model.