Optic nerve hypoplasia and growth hormone deficiency in a cholestatic infant

This report describes a 4-month-old male with cholestasis, hypoglycemia, and short stature. Symptoms appeared since neonatal age with jaundice, hypoglycemia, neurologic manifestations, and later with short stature. Laboratory investigation was indicative for cholestasis. Further research indicated isolated growth hormone deficiency with accompanying optic nerve hypoplasia. Unexplained hypoglycemia and cholestasis in neonates have to be investigated for growth hormone deficiency. Moreover, in cases with unexplained cholestasis, timely recognition of hypoglycemia is important for the early diagnosis of the disorder before the appearance of growth retardation.     

Serial blood donations for intrauterine transfusions of severe hemolytic disease of the newborn with the use of recombinant erythropoietin in a pregnant woman alloimmunized with anti-Ku

BACKGROUND: The management of a pregnant woman with the rare Ko phenotype and anti-Ku is a special challenge, because matched blood is extremely rare and the possibility of severe hemolytic disease of the newborn is high. CASE REPORT: A 30-year-old woman with rare Ko (Knull) phenotype presented at 18 weeks of gestation with positive indirect agglutination test results. She had anti-Ku due to previous blood transfusion, one pregnancy, and two abortions. STUDY DESIGN AND METHODS: During this pregnancy, anti-Ku titers ranged from 1024 to 4096. At the 26th week of gestation ultrasound showed a hydropic fetus and urgent intrauterine exchange transfusion was performed with the maternal red blood cells (RBCs). Recombinant human erythropoietin (rHu-EPO) and intravenous (IV) iron were administered to the mother to ensure an adequate supply of matched RBCs for intrauterine transfusions and possible perinatal hemorrhage. RESULTS: Intrauterine transfusions were repeated every 1 to 3 weeks. By 35 weeks 2 days of gestation, the mother had donated 4 units of blood, and four intrauterine transfusions had been performed. Cesarean section was then decided and a healthy male newborn was born. He was treated with phototherapy but without exchange transfusions. By the 15th day of life rHu-EPO was administrated to the newborn because of anemia. The maternal RBCs completely disappeared from the child's blood by Day 100. CONCLUSIONS: As shown in this case, treatment with rHu-EPO and IV Fe has effectively increased the mother's capacity to donate RBCs for autologous use and intrauterine transfusions, with no adverse effects to the mother or the child.     

Stüve–Wiedemann syndrome in a neonate

We describe a female neonate with Stüve–Wiedemann syndrome. The facial dysmorphism, joint contracture, distinctive skeletal changes, and myotonic discharges on electromyogram raised a suspicion of the rare autosomal recessive syndrome, which was later confirmed on molecular analysis of leukemia inhibitory factor receptor. She developed recurrent attacks of hyperpyrexia and died at age 3 months.     

A Rare Case of a Male with 45, XO, SRY+, ZFY+ with Short Stature and Mild Turner Stigmata

Background: Turner syndrome is hypothesized to result from haploinsufficiency of certain genes expressed from both sex chromosomes that escape X inactivation. Case Report: We present the rare case of a 4-year-old boy who was referred to the pediatric endocrinology unit for evaluation of slight growth delay. Results: Standard cytogenetic analysis showed a 45,XO karyotype. Molecular studies disclosed the presence of an intact SRY homeobox region and the ZFY region sited on the Y short arm. Other Y chromosome sequences which are normally found on the short arm of chromosome Y (p) were absent and their exact location on a different chromosome remained unclear. Subsequently, FISH (fluorescent in situ hybridization) analysis failed to detect any Y sequences, while haplotype analysis indicated that the present X chromosome was of paternal origin. Conclusion: Phenotype-genotype correlation studies were consistent with a male patient presenting with short stature and some of the Turner's syndrome stigmata. The consequences for the patients with this chromosomal abnormality and treatment with recombinant growth hormone are also discussed.     

The renin-angiotensin-aldosterone axis in patients with nontumoral [corrected] hyperprolactinemia

Objective In physiological conditions, renin–angiotensin–aldosterone (RAA) axis is under continuous tonic inhibition by dopamine. The aim of this study was to evaluate the relationship of nontumoural hyperprolactinemia with the activity of adrenocortical and RAA axis, before and after administration of bromocriptine. Design Twenty women with nontumoural hyperprolactinemia and 20 healthy women matched for body mass index and age were recruited in this study. All participants were placed on fixed salt intake for 2 weeks before the experiments. The study was conducted in three phases. In phase I, the participants received an intravenous infusion of angiotensin II in three consecutive doses of 2, 4 and 6 ng/kg BW changed every 30 min. In phase II, the patients were started on bromocriptine in gradually increasing doses of 1·25, 2·5, 5, 7·5 and 10 mg/day for 10 weeks. In phase III, the protocol of phase I was repeated in the patient group. Circulating levels of cortisol, plasma renin activity (PRA), aldosterone and prolactin were assayed. Results Baseline values of prolactin, and PRA (2·6 ± 0·18 nm vs 0·45 ± 0·05 nm P < 0·001 and 142·2 ± 14·4 vs 30·7 ± 2·7 pm /h, P < 0·001, respectively) but not aldosterone (P = 0·081) were significantly higher in the patient group. The angiotensin infusion test induced a significantly greater response in the patient group. Administration of the dopamine agonist restored the basal levels and diminished the response to angiotensin infusion for all the parameters tested. No change in the blood pressure was recorded. Conclusions Our study demonstrates that in nontumoural hyperprolactinemia there is an increased reactivity of renin–angiotensin–aldosterone (RAA) axis that is almost completely restored after treatment with a dopamine agonist.     

Ultrasound velocity through the cortex of phalanges,radius, and tibia in normal and osteoporotic postmenopausal women using a new multisite quantitative ultrasound device

RATIONALE AND OBJECTIVES: To assess a new multisite quantitative ultrasound (QUS) device (Sunlight Omnisense 7000 S) suitable for the measurement of speed of sound (SOS) in the phalanges, radius, and tibia. METHODS: The study group consisted of 270 healthy Caucasian postmenopausal patients (mean age: 60.0 +/- 7.6 years) and 53 Caucasian postmenopausal patients (mean age: 67.2 +/- 7.4 years) with osteoporotic fractures. Measurements of SOS and bone mineral density (BMD) were carried out in all subjects. RESULTS: Intraobserver in vivo short-term precision was on average 0.76% for the radius, 0.47% for the tibia, and 1.54% for the phalanges. The interobserver precision ranged from 0.77% to 2.39%. Measurements of SOS at the 3 skeletal sites were significantly correlated (r = 0.28-0.44; P < 0.001). Significant correlations were found between SOS at all sites and BMD (r = 0.21-0.41; P < 0.001). The odds ratio for fracture prediction for SOS was 1.47 for tibia, 1.69 for radius, and 2.69 for phalanx. The corresponding odds ratios for BMD at the lumbar spine, femoral neck, and total hip ranged from 2.08 to 3.26. The area under the receiver operating characteristic curve ranged from 0.611 to 0.741 for SOS measurements and from 0.745 to 0.797 for BMD measurements. CONCLUSIONS: The Omnisense multisite QUS device exhibits reproducible performance. Among the QUS variables, the phalangeal SOS provides the best discrimination of fracture patients.     

Checkpoint abrogation in G2 compromises repair of chromosomal breaks in ataxia telangiectasia cells

Checkpoint abrogation in G(2) compromises repair of DNA double-strand breaks (DSB) and confers enhanced G(2) chromosomal radiosensitivity in ataxia telangiectasia (AT) cells. To directly test this hypothesis, we combined calyculin A-induced premature chromosome condensation with conventional cytogenetics to evaluate chromosome damage before and after the G(2) checkpoint in irradiated primary AT and normal human lymphocytes and their lymphoblastoid derivatives. Direct analysis of radiation damage in G(2) by premature chromosome condensation reveals practically indistinguishable levels of chromosomal breaks in AT and normal cells. Yet a 4-fold increase in metaphase chromosome damage is observed in AT cells as compared with normal cells which, in contrast to AT cells, exhibit a strong G(2) arrest manifest as an abrupt reduction in the mitotic index. Thus, an active checkpoint facilitates repair of chromosomal breaks in normal cells. Treatment with caffeine that abrogates the G(2) checkpoint without significantly affecting DSB rejoining increases metaphase chromosome damage of normal cells to the AT level but leaves unchanged interphase chromosome damage in G(2). Caffeine has no effect on any of these end points in AT cells. These observations represent the first direct evidence that the G(2) checkpoint facilitates repair of chromosome damage, presumably by supporting repair of DNA DSBs. Failure to arrest will lead to chromatin condensation and conversion of unrepaired DNA DSBs to chromosomal breaks during G(2)-to-M phase transition.