Robert Denis

Clinical value of a single postnatal lactate measurement after intrapartum asphyxia

Our aim was to compare the respective values of base deficit and lactate in birth asphyxia. Methods: Base deficit and lactate levels were measured from radial artery blood samples taken at 30min of life in 115 term newborns suspected as having been asphyxiated during labour. Both base deficit and lactate levels were compared between patients who further developed moderate or severe encephalopathy and those who experienced no or only mild encephalopathy. Receiver operating characteristics curves and clinical values of both indicators were computed. Results: The correlation between base deficit and lactate was significant (r2= 0.51, p < 0.0001). Both indicators were significantly associated with neonatal outcome. Lactacidaemia lower than 5 mmol/l and/or base deficit level lower than 10 mEq/l were not followed by neurological complications. Plasma lactate concentration greater than 9 mmol/l was associated with moderate or severe encephalopathy with a sensitivity of 84% and a specificity of 67%. Base deficit and lactate had similar clinical values.

A simple method for measuring separate glomerular filtration rate using a single injection of 99mTc-DTPA and the scintillation camera

A new technique for measuring glomerular filtration in each kidney has been developed using a scintillation camera and the 99mTc-DTPA complex. The technique has been applied to 101 children with various uropathies. Correlations with the total and separate creatinine clearance, the HgCl2 uptake test, and the maximal urinary concentration have been good. The reproducibility of the method has been satisfactory in a small number of patients. The test is particularly adapted to children because of its simplicity, reduced trauma, short duration (20 minutes) and low-radiation dose. In contrast to some other radioisotope techniques, it can be carried out in infants.

Pyruvate-dehydrogenase Deficiency - Clinical and Biochemical-diagnosis

A female neonate with pyruvate dehydrogenase (PDH) deficiency is presented with clinical, radiologic, biochemical, neuropathologic, and molecular genetic data. She was dysmorphic, with a high forehead, lowset ears, thin upper lip, upturned nose, and rhizomelic limbs. Cranial MRI revealed severe cortical atrophy, ventricular dilatation, and corpus callosum agenesis. Pyruvate and lactate levels were increased in CSF and blood. Urinary organic acid profile was compatible with PDH deficiency. PDH activity was normal in fibroblasts, lymphocytes, and muscle. The PDH E1-alpha gene was sequenced and a single base mutation was found within the regulatory phosphorylation site in exon 10. It is postulated that this mutation causes a cerebral form of PDH deficiency. Tissue-specific expression of the disease could be explained by differential X chromosome inactivation because the PDH E1-alpha gene is located on this chromosome. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF.

Neuropathological Findings of a Patient With Pyruvate Dehydrogenase-e1-alpha Deficiency Presenting As a Cerebral Lactic-acidosis

SummaryNeuropathological findings are reported of a 6-month-old female child with a “cerebral” lactic acidosis. A mutation in the pyruvate dehydrogenase (PDH) E1α gene was found. Gross examination of the brain revealed a severe thinning of the cerebral parenchym, a marked hydrocephalus sparing the aqueduct and fourth ventricle, agenesis of the corpus callosum and heterotopic noduli of gray matter in subependymal regions. Microscopical examination showed heterotopic inferior olives, absent pyramids and focal neuroglial overgrowth into meninges. In addition some heterotopia of Purkinje cells and dysplasia of the dentate nuclei were observed. There was a marked vascular proliferation with many thin-walled, congestive vessels in the cerebral and cerebellar white matter, and to a lesser extent in the striatum. To our knowledge these cerebellar and vascular abnormalities have not been reported before in patients with “cerebral” lactic acidosis. The combination of these neuropathological findings might be characteristic for PDH deficiency and more specifically for its E1α subtype. Neuropathological examination could lead to the retrospective diagnosis of PDH E1α deficiency in those cases where biochemical investigations were not or incompletely performed. This may have potential implications for genetic counseling.

Hyperphosphatasemia in early diagnosed infantile GM1 gangliosidosis presenting as transient hydrops fetalis.

The authors report a case of unsuspected fetal storage disorder initially diagnosed by placental examination performed because of a transient ascites at 28 weeks of gestation. At birth mild dysmorphic features and gradual neurological deterioration were observed. Highly elevated alkaline phosphatase levels were repeatedly noticed. Deficiency of beta-galactosidase was documented confirming GM1 gangliosidosis. Previous reports described the placental pathology after positive prenatal diagnoses of lysosomal diseases. In the present case, the postnatal diagnosis was made in view of the placental pathologic findings. Our observation indicates the need for thorough investigations in hydrops fetalis, in search for metabolic diseases.