D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity?

D-2-Hydroxyglutaric aciduria has been observed in patients with extremely variable clinical symptoms, creating doubt about the existence of a disease entity related to the biochemical finding. An international survey of patients with D-2-hydroxyglutaric aciduria was initiated to solve this issue. The clinical history, neuroimaging, and biochemical findings of 17 patients were studied. Ten of the patients had a severe early-infantile-onset encephalopathy characterized by epilepsy, hypotonia, cerebral visual failure, and little development. Five of these patients had a cardiomyopathy. In neuroimaging, all patients had a mild ventriculomegaly, often enlarged frontal subarachnoid spaces and subdural effusions, and always signs of delayed cerebral maturation. In all patients who underwent neuroimaging before 6 months, subependymal cysts over the head or corpus of the caudate nucleus were noted. Seven patients had a much milder and variable clinical picture, most often characterized by mental retardation, hypotonia, and macrocephaly, but sometimes no related clinical problems. Neuroimaging findings in 3 patients variably showed delayed cerebral maturation, ventriculomegaly, or subependymal cysts. Biochemical findings included elevations of D-2-hydroxyglutaric acid in urine, plasma, and cerebrospinal fluid in both groups. Cerebrospinal fluid gamma-aminobutyric acid was elevated in almost all patients investigated. Urinary citric acid cycle intermediates were variably elevated. The conclusion of the study is that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with at least two phenotypes.

Cohorting of infants with respiratory syncytial virus.

During two winter periods (1994-1995 and 1995-1996), nasopharyngeal aspirates were obtained from infants and young children with an acute respiratory illness, after initial assessment in an area with six cubicles which serves as an admissions unit. Aspirates were sent for rapid diagnostic testing. Respiratory syncytial virus (RSV) positive patients were cohorted into two six-bedded bays on the paediatric wards. Over the two successive winter periods studied, 347 RSV positive patients were assigned to the cohort. No nosocomial infections were identified during the first winter; in the second, two were identified. Cohorting at admission eased clinical management, with one area used for high-dependency care and cubicles being freed for children with other infectious diseases. Nosocomial infection was minimized.

Continuous negative extrathoracic pressure in neonatal respiratory failure.

OBJECTIVE: In uncontrolled clinical trials, negative extrathoracic pressure has been shown to be an effective respiratory support. We aimed to assess its role in the context of current neonatal intensive care. DESIGN: A randomized controlled trial, with sequential analysis of matched pairs of infants. Matching was undertaken by stratified randomization from 15 groups divided according to gestational age, oxygen requirement, and whether patients were intubated at 4 hours of age. SETTING: Two neonatal intensive care units. PATIENTS: Two hundred forty-four patients (birth weight 1.53 +/- 0.69 kg (mean +/- SD); gestational age 30.4 +/- 3.5 weeks) with respiratory failure. INTERVENTIONS: Patients were randomized at 4 hours of age to receive either standard neonatal intensive care, or standard care plus continuous negative extrathoracic pressure (CNEP, -4 to -6 cmH2O) applied within a purpose-designed neonatal incubator. OUTCOME SCORES: Clinical scores were calculated for each infant at 56 days of age, or death if earlier. Scores included measures for mortality, respiratory outcome, the presence of cerebral ultrasound abnormalities, patent arterial duct, necrotizing enterocolitis, and retinopathy. The treatment given for the higher score for each pair was recorded and the cumulative net number of pairs favoring CNEP plotted in the sequential analysis to provide an ethical early termination strategy. Individual components of the outcome score and other secondary measurements were analyzed on completion of the trial. RESULTS: The sequential analysis reached a decision boundary after 122 out of a possible maximum of 124 pairs were completed. The overall outcome score showed an overall significant benefit for CNEP. Secondary analysis showed that the use of CNEP was associated with an increase in mortality, cranial ultrasound abnormalities, and pneumothoraces, which were not statistically significant. However, 5% fewer patients were intubated (95% confidence interval [CI], 0-10), and the total duration of oxygen therapy among surviving infants at 56 days was lower (20.5 days, compared with 38.9 in controls; difference 18.4 days, 95% CI 3.8 to 33.0). Among all infants, the mean total duration of oxygen therapy was 18.3 days among CNEP-treated infants compared with 33.6 days among the controls (difference -15.3 days, 95% CI -0.2 to -30.4). This reduction in mean levels is entirely attributable to substantially fewer patients requiring prolonged oxygen therapy, the median duration of treatment being very similar in the two groups. As a result, commensurately fewer surviving infants showed chronic lung disease of prematurity. CONCLUSIONS: The use of continuous negative pressure improves the respiratory outcome for neonates with respiratory failure.

A case of congenital chylothorax treated by pleuroperitoneal drainage.

A congenital chylothorax that necessitated recurrent pleural taps was successfully treated by a pleuroperitoneal shunt that was inserted when the infant was 28 days old. Further thoracentesis was avoided and failure to thrive was overcome.

The importance of late pregnancy scans for renal tract abnormalities.

A 12-month prospective population study of antenatal patients was undertaken in a large district general hospital to assess ultrasound scanning in late pregnancy for the detection of non-lethal fetal renal abnormalities. The rate of false-negative antenatal scans during the study period was also assessed. Both 18-20 and 28-32 weeks' gestational scans were performed on 6497 pregnant women. Forty fetuses with a suspected abnormality were referred for postnatal examination and 29 neonates were found to have renal abnormalities. Of these, 21 were significant and eight were likely to be extrarenal pelves. In six, there was evidence of an abnormality at the early scan. Nine children, seven with reflux, presented within the study period, all with preceding normal antenatal scans. The incidence (0.46 per cent) of structural renal abnormalities is similar to that reported previously. A late scan is necessary for the antenatal detection of non-lethal renal abnormalities.

Antenatal ultrasonography to detect fetal renal abnormalities: a prospective screening programme.

OBJECTIVE: To evaluate screening for abnormalities of the fetal renal tract by ultrasonography and to determine the incidence of such abnormalities in a population. DESIGN: A 12 month prospective population study. Follow up of infants to between 9 and 18 months. SETTING: A district general hospital. PARTICIPANTS: 6292 Pregnant women reaching 28 weeks' gestation within the study period. INTERVENTIONS: Antenatal ultrasound scanning was offered to all of the women. Babies in whom an abnormality of the renal tract had been detected antenatally underwent ultrasound scanning at the end of the first week. If the abnormality was confirmed contrast radiography was performed. END POINT: Confirmation of suspected renal abnormality by postnatal investigations. Detection of abnormality in children thought to be normal antenatally. MEASUREMENTS AND MAIN RESULTS: Of the 92 babies who had abnormal antenatal scans, 42 had abnormalities confirmed postnatally. Four of them died and 21 had had or were awaiting an operation at 18 months' follow up. Seven children had renal abnormalities that were missed antenatally. The incidence of abnormalities detected by screening antenatally was 0.65%, and the overall incidence at 18 months' follow up was 0.76%. CONCLUSIONS: The incidence of structural renal abnormalities in babies is higher than reported previously. Antenatal ultrasonography is an effective way of detecting such abnormalities.

Developmental outcome of high-risk neonates in North Staffordshire.

The findings of the developmental outcome of a 2-year follow-up study (1982-1983) on 92 2 1/2-year-old children born in North Staffordshire District are reported. They were assessed by the Griffiths Mental Developmental Scales and all came from a defined geographical area. The babies were all cared for in the Neonatal Unit at the North Staffordshire Maternity Hospital. The group comprised infants weighing less than 1500 g and those of more than 1500 g who required ventilatory support for more than 48 hours. Nine (9.8%) children had major disabilities, including two with severe hearing impairment and two with visual impairment. Disabilities were not attributable to a congenital abnormality or illness acquired after discharge from the neonatal unit.

Detection of abnormality of fetal urinary tract as a predictor of renal tract disease.

Over three years all infants in this hospital found to have an abnormality of the urinary tract on antenatal scanning were followed up after delivery with contrast radiography. Disease of the renal tract was confirmed in 17 of 20 infants. Of the 15 survivors, 12 underwent surgery in the first year of life. Abnormality of the fetal urinary tract detected by ultrasound scanning seems to be an important indicator of disease of the renal tract. Before its use is extended, however, further assessment of the benefit of antenatal diagnosis and of the best time to scan is required.

Small bowel biopsy.

We describe our technique of small bowel biopsy, which has been used on 190 occasions over a four year period. In 77%, the examination was completed within 10 minutes, and fluoroscopy times were less than 10 seconds in 75% of the cases. The technique is easily taught, and it has made the examination a minor procedure.

An outbreak of Serratia marcescens infections in a neonatal unit.

Over a 15-month period 732 babies were admitted to a neonatal unit, and Serratia marcescens was isolated from 153 (21%). In one-fifth (34) a clinical infection (9 major and 25 minor) developed. Major infection was associated with high mortality and morbidity and 2 cases presented after the neonatal period. No environmental reservoir was found. Colonised symptom-free neonates were considered to be the source, with transmission by staff-baby contact despite adequate hand-washing. Overcrowding was believed to be responsible for the difficulties experienced in eradicating this transmission.

A case of ring chromosome.

A girl with a G22 ring chromosome is described. There are few physical abnormalities, performance quotient is in the low normal range but verbal skills are much retarded.

Thyrotoxicosis in a neonate of a mother with no history of thyroid disease.

A newborn infant had rectal prolapse, congenital lactase deficiency, and temporary neonatal thyrotoxicosis. The thyrotoxicosis was associated with a raised long-acting thyroid stimulator index in a mother with no personal or family history of thyroid or related autoimmune disease. The parents were first cousins.