Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening

Tandem mass spectrometry was adopted for newborn screening by North Carolina in April 1999. Since then, three infants with short-chain acyl-CoA dehydrogenase (SCAD) and one with isobutyryl-CoA dehydrogenase deficiency were detected on the basis of elevated butyrylcarnitine/isobutyrylcarnitine (C4-carnitine) concentrations in newborn blood spots analyzed by tandem mass spectrometry. For three SCAD-deficient infants, biochemical evaluation included a plasma acylcarnitine profile with markedly elevated C4-carnitine, urine organic acid analysis with markedly elevated ethylmalonic and 2-methylsuccinic acids, and markedly elevated [U-13C]butyrylcarnitine concentrations in medium from fibroblasts incubated with [U-13C]palmitic acid and excess l-carnitine, consistent with classic SCAD deficiency. Two of three infants diagnosed with classic SCAD deficiency remained asymptomatic; however, the third infant presented with seizures and a cerebral infarct at 10 wk of age. All three infants had putatively inactivating mutations in both alleles of the SCAD gene. The highly elevated plasma C4-carnitine levels in the three infants detected by newborn screening tandem mass spectrometry differentiated them from infants and children who were homozygous or compound heterozygous for one of two SCAD gene susceptibility variations; for the latter group the C4-carnitine levels were normal. Isobutyryl-CoA dehydrogenase deficiency in a fourth infant was confirmed after isolated elevation of C4-carnitine in the acylcarnitine profile.     

Glutaric acidemia, type I, missed by newborn screening in an infant with dystonia following promethazine administration

We report a child initially diagnosed with promethazine-induced dystonia despite a lack of response to diphenhydramine therapy. On further evaluation, the child was diagnosed with glutaric acidemia, type I (GA-I), an autosomal recessive inborn error of metabolism caused by the deficiency of glutaryl-CoA dehydrogenase. The characteristic clinical feature of GA-I is an acute encephalopathic and neurologic crisis typically occurring during a catabolic state. Despite slow improvement, many patients do not fully recover from a neurologic crisis, and residual neurologic morbidity can be significant. Although newborn screening using tandem mass spectrometry is expected to enable presymptomatic diagnosis of GA-I, this patient was not detected by newborn screening with tandem mass spectrometry. Therefore, a high suspicion of GA-I must be maintained in the evaluation of childhood dystonia, even when newborn screening results are reportedly normal.     

Mammographic findings after breast cancer treatment with local excision and definitive irradiation

Following local excision and definitive irradiation of 163 breast cancers in 160 women, alterations in mammographic patterns were observed for up to 7 years. Skin thickening was observed in 96% of mammograms obtained within 1 year of completing therapy and was most pronounced in women treated with iridium implant, chemotherapy, or axillary dissection. In 76% of mammograms, alterations in the parenchymal pattern, including coarsening of stroma and increased breast density, were seen at 1 year. Neither skin nor parenchymal changes progressed after 1 year. Within 3 years of treatment the parenchymal density, which usually regressed, did not change in all patients. At 3 years skin thickness and the parenchymal pattern had returned to normal in less than 50% of the breasts of these women. Scars developed in approximately one-quarter of women. They were present on the initial post-treatment mammogram and remained unchanged on serial studies. Coarse, benign calcifications also developed in the breasts of about one-quarter of women. Microcalcifications developed in 11 breasts; biopsy specimens of six were benign. Benign microcalcifications may be related to therapy.     

Lymphangiomas in children: MR imaging

Seventeen lymphangiomas in 15 patients were imaged with magnetic resonance (MR) to define the nature, extent, and anatomic relationships of these lesions. The MR and pathologic findings were then compared to determine the histologic basis for the signal-intensity characteristics of these lesions. The signal intensity of 13 lesions was similar to or slightly less than that of muscle on T1-weighted images and greater than that of fat on T2-weighted images. This appearance correlated with the presence of ectatic lymphatic channels containing clear fluid on histologic section. Four lymphangiomas had high signal intensity, approximately equal to that of fat, on T1-weighted images, reflecting the presence of clotted blood or small cystic spaces with a higher ratio of fat to fluid. Sixteen of 17 lesions had visible septations on MR images. The authors' experience suggests that most lymphangiomas have a characteristic appearance on MR images. The information obtained with MR imaging can help in providing a preoperative diagnosis, in planning surgical resection, and in defining recurrence.     

Liver metastases: detection by phase-contrast MR imaging

Forty patients with biopsy-proved metastatic liver cancers were studied by magnetic resonance (MR) imaging using one or more conventional (in-phase) pulse sequences and a corresponding phase-contrast (opposed-phase) pulse sequence. Pulse-sequence performance was quantitated by measuring signal-difference-to-noise (SD/N) ratios between cancerous tissue and liver. The SD/N performance of T2-weighted spin-echo (SE) pulse sequences improved when used with the phase-contrast technique. SE 2,000/30 opposed-phase images showed improved (P less than .001) SD/N in 72% of patients over in-phase images. The SD/N of T1-weighted SE or inversion recovery pulse sequences deteriorated when used with the phase-contrast technique. Changes in measured SD/N correlated well with image appearance and actual lesion detectability in individual cases. Phase-contrast imaging should be employed routinely when T2-weighted SE pulse sequences are relied on to detect liver cancer.     

Low-speed rotational angioplasty in chronic peripheral artery occlusions: experience in 83 patients. Work in progress

Between December 1986 and October 1988, 83 patients with chronic peripheral artery occlusions were treated with a new technique. In 56 patients, the superficial femoral artery was completely occluded; in 21 patients, the popliteal artery; and in six patients, the iliac artery. The length of occlusion ranged from 5 to 35 cm (mean, 12.5 cm). The duration, estimated by history, was 5-48 months (mean, 16.5 months). In seven patients, durations of 6-36 months were documented angiographically. A flexible, blunt, motor-driven rotating catheter was introduced through an 8-F sheath, and rotational angioplasty was performed at low speed (up to 200 rpm). In 49 of 60 (82%) patients in whom this new technique was used as the primary intervention, the occlusions were successfully reopened. In 23 patients in whom conventional methods had failed more than 4 weeks earlier, the success rate for rotational angioplasty was 67% (12 of 18 patients); when the time interval was less than 4 weeks, only one of five patients was treated successfully. In none of the 83 patients did a perforation occur. This new technique can reopen chronic artery occlusions with a high degree of success and without the danger of vessel-wall perforation, even after failure of conventional techniques.     

Using Instrumental Neutron Activation Analysis for geochemical analyses of terrestrial impact structures: Current analytical procedures at the University of Vienna Geochemistry Activation Analysis Laboratory

The Instrumental Neutron Activation Analysis Gamma Spectroscopy Laboratory at the Department of Lithospheric Research, University of Vienna, has been upgraded in the year 2006. This paper describes the sample preparation, new instrumentation and data evaluation for hundreds of rock samples of two terrestrial impact structures. The measurement and data evaluation are done by using Genie™ 2000 and a custom-made batch software for the used analysis sequences.