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Biomedical subjects

P Landrieu

Publications and source records attributed to P Landrieu.

At least 19 recordsLinked to original sources
PubMed1997

Segregation of the G8993 mutant mitochondrial DNA through generations and embryonic tissues in a family at risk of Leigh syndrome.

We identified the T8993G mitochondrial mutation in a female infant who died of Leigh syndrome. The proportion of mutant mitochondrial DNA increased to near homoplasmy in three generations of the pedigree. A similarly high proportion of mutant mitochondrial DNA was found in the chorionic villi and in fetal tissues from a pregnancy interrupted because of the risk of Leigh syndrome. This study supports the concept that prenatal diagnosis can be used for Leigh syndrome with the T8993G mitochondrial DNA mutation.

Abortion, Therapeutic↗
PubMed1997

[Ischemic cerebral vascular accident caused by vertebral artery dissection].

BACKGROUND: Strokes due to vertebral artery lesions are not yet well known in children. CASE REPORT: We report on a case of post-traumatic vertebral artery dissection responsible for ischemic stroke in a 8-year old boy. Headache, vomiting and a brief loss of consciousness were the main initial signs. Neurological examination showed a locked-in syndrome. Cerebral imaging revealed lesions in cortical cerebellar hemisphere, cerebral pedoncular and protuberance. An arteriogram performed on day 10 showed left vertebral artery occlusion at C2 levels consistent with vertebral dissection. Antiagregants treatment was given. Neurological recovery was good. Pertinent clinical data of 24 children who had strokes due to a vertebral artery dissection are analysed. CONCLUSION: Vertebral artery dissection is presently a well-known cause of childhood strokes. Benefits from anticoagulants are now established.

Aortic Dissection↗
PubMed1997

High dose methylprednisolone in severe acute transverse myelopathy.

No effective treatment has been shown for patients with acute transverse myelopathy. In an open study five children with severe acute transverse myelopathy were treated with intravenous methylprednisolone and compared with a historical group of 10 patients. The results show that in the methylprednisolone treatment group compared with the historical group of 10 patients: the median time to walk independently was significantly reduced (23 v 97 days); the proportion of patients with a full recovery within 12 months was significantly higher (80 v 10%); all patients had complete motor recovery within one year in contrast with only two of 10 patients in the historical group; and serious adverse effects did not occur. This pilot study suggests that high dose methylprednisolone is effective in the treatment of acute transverse myelopathy.

Acute Disease↗
PubMed1996

Survival motor neuron gene deletion in the arthrogryposis multiplex congenita-spinal muscular atrophy association.

The survival motor neuron (SMN) gene was lacking in 6/12 patients with arthrogryposis multiplex congenita (AMC) associated with spinal muscular atrophy (SMA). Neither point mutation in the SMN gene nor evidence for linkage to chromosome 5q13 were found in the other patients. Hitherto, arthrogryposis was regarded as an exclusion criterion in SMA. Our data strongly suggest that AMC of neurogenic origin is genetically heterogeneous, with a subgroup being allelic to SMA. Absence or interruption of the SMN gene in the AMC-SMA association will make the diagnosis easier and genetic counselling will now become feasible.

Arthrogryposis↗
PubMed1996

Aggregation of a subpopulation of vimentin filaments in cultured human skin fibroblasts derived from patients with giant axonal neuropathy.

Giant axonal neuropathy (GAN) is a generalized disorder of intermediate filament networks which results in the formation of an ovoid aggregate in a large variety of cell types. We investigated the cytoskeletal organization of cultured skin fibroblasts derived from three GAN patients by indirect immunofluorescence, confocal, and electron microscopy. Whereas the organization of microfilaments seemed normal, the microtubule network appeared disorganized and tangled. The organization of the intermediate filament network, composed of vimentin, was probed with three antibodies directed against different epitopes: two vimentin-specific antibodies, a monoclonal antibody (mAb V9) and a polyclonal antibody, and a serum specific for all type III IFPs (PI serum). These experiments showed that 20% of cultured skin fibroblasts from GAN patients have a vimentin aggregate composed of densely packed filaments which coexists with a well-organized vimentin network. After depolymerization of microtubules with nocodazole, all fibroblasts from GAN patients contained a vimentin aggregate which seemed to arise from a subpopulation of vimentin filaments normally integrated in the vimentin network. Such aggregates were never observed in any condition in control fibroblasts. Moreover, the ultrastructural analysis of GAN cells revealed the presence of swollen mitochondria. We suggest that GAN may be due to a defect in a factor which stabilizes cytoplasmic intermediate filament networks, and we speculate on its identification and properties.

Actin Cytoskeleton↗
PubMed1996

[Primary amenorrhea revealing congenital hydrocephalus].

UNLABELLED: Among the various endocrine manifestations of chronic hydrocephaly, amenorrhea is not exceptional, whereas late puberty and obesity are the most frequent. The hypothalamic gonadotropic function usually returns to normal within the few months following the ventricular shunt. CASE REPORT: A 16 year-old girl, with a von Recklinghausen's disease, developed amenorrhea 2 years after the onset of puberty. X-rays of her skull showed an enlarged sella turcica and a diagnosis of hydrocephalus due to aqueductal stenosis was finally made. As her head circumference was retrospectively shown at +3 SD as early as the first month of life, the stenosis was certainly congenital, a feature known to occur in 2% of patients with von-Recklinghausen's disease. CONCLUSION: In symptomatic forms of aqueductal stenosis, the preferred surgical procedure is ventriculocisternostomy under endoscopy. Recovery of intellectual functions is often incomplete. Early diagnosis of hydrocephalus is of paramount importance; ultrasonography through anterior fontanel should be proposed to any infant with head circumference reaching +3 SD.

Adolescent↗
PubMed1996

Congenital unilateral perisylvian syndrome: radiological basis and clinical correlations.

DESIGN: Advances in neuroimaging have allowed correlations between radiological patterns and clinical features of brain malformations. This paper reports clinical, prognosis, and electroencephalographic features of six children with a previously unrecognised neuroimaging picture of unilateral widening and verticalisation of the sylvian fossa associated with an abnormal ipsilateral perisylvian cortex. RESULTS: All children had reduced hemisphere size and thalamostriatal hypoplasia ipsilateral to the cleft and hemiplegia. Cognitive development was mostly impaired. Epilepsy occurred in two patients and was mainly characterised by partial seizures. Studies with EEG showed hemispheric slowing of background activity homolateral to the perisylvian dysplasia. Occurrence of the malformation among their siblings was not found. CONCLUSION: Similar brain malformations occasionally reported in older patients confirm the clinical picture, sporadic occurrence, and prognosis found, allowing the validation of a unilateral perisylvian syndrome.

Brain↗
PubMed1996

Extensive brain calcifications, leukodystrophy, and formation of parenchymal cysts: a new progressive disorder due to diffuse cerebral microangiopathy.

A new cerebral disorder, described in three unrelated children, has recognizable clinical, radiologic, and neuropathologic findings. The onset occurs from early infancy to adolescence with slowing of cognitive performance, rare convulsive seizures, and a mixture of extrapyramidal, cerebellar, and pyramidal signs. CT shows progressive calcifications in the basal and cerebellar gray nuclei and the central white matter. MRI reveals diffuse abnormal signals of the white matter on T2-weighted sequences. A special feature is the development of parenchymal cysts in the cerebellum and the supratentorial compartment, leading to compressive complications and surgical considerations. Neuropathologic examination of surgically removed pericystic samples reveals angiomatous-like rearrangements of the microvessels, together with degenerative secondary changes of other cellular elements. Both the anatomic findings and the course of the disease suggest a constitutional, diffuse cerebral microangiopathy resulting in microcystic, then macrocystic, parenchymal degeneration.

Brain Diseases↗
PubMed1996

Analysis of a splice-site mutation in the sap-precursor gene of a patient with metachromatic leukodystrophy.

Sphingolipid activator proteins (SAPs) are small, nonenzymatic glycoproteins required for the lysosomal degradation of various sphingolipids with a short oligosaccharide chain by their exohydrolases. Four of the five known activator proteins (sap-A-sap-D), also called "saposins," are derived from a common precursor by proteolytic processing. sap-B stimulates hydrolysis of sulfatides by arylsulfatase A in vivo. Its recessively inherited deficiency results in a metabolic disorder similar to classical metachromatic leukodystrophy, which is caused by a defect of arylsulfatase A. Here we report on a patient with sap-B deficiency. Reverse-transcription-PCR studies on the patient's mRNA revealed the occurrence of two distinct mutant species: one with an in-frame deletion of the first 21 bases of exon 6, the other with a complete in-frame deletion of this exon. The patient was homozygous for the underlying mutation, which was found to be a G-->T transversion within the acceptor splice site between intron e and exon 6, abolishing normal RNA splicing. Allele-specific oligonucleotide hybridization revealed that the parents and both grandfathers of the patient were carriers of this mutation. In order to analyze the fate of the mutant precursor proteins, both abnormal cDNAs were stably expressed in baby hamster kidney cells. Pulse-chase experiments showed that the deletion of 21 bp had no effect on the transport and the maturation of the encoded precursor. All sap forms except sap-B were detectable by immunochemical methods. The cDNA bearing a complete deletion of exon 6 encoded a shortened precursor of only 60 kD, and no mature SAPs were detectable. The carbohydrate chains of this polypeptide were of the high-mannose and hybrid type, indicating no transport of the mutant precursor beyond early Golgi apparatus. An endoplasmic-reticulum localization of this polypeptide was supported by indirect immunofluorescence analysis.

Animals↗
PubMed1995

Familial isolated vitamin E deficiency. Extensive study of a large family with a 5-year therapeutic follow-up.

A major neurological deterioration, beginning with ataxia, led to the diagnosis of familial vitamin E deficiency in a girl. Based upon vitamin E determinations, 4/8 members of the (consanguineous) sibship were considered to be homozygous. Homozygosity was also found for the alleles of six markers linked to the AVED locus, recently identified in similar Tunisian or Sicilian families on chromosome 8q. Measures of vitamin E in lipoprotein fractions and in liver biopsy after vitamin E oral load suggested that free diffusion of vitamin E between the different compartments was possible and even increased. However, a high-affinity ligand seemed to be lacking, either in the hepatic recycling of vitamin E or in both the hepatic and the other vitamin E compartments. The 5-year substitutive treatment was successful only in the pre- or paucisymptomatic patients. Serum vitamin E must be measured in any unexplained progressive ataxia.

Adolescent↗
PubMed1995

[Encephalopathy induced by arterial hypertension: clinical, radiological and therapeutical aspects].

BACKGROUND: Neuroradiological features of hypertensive encephalopathy are not yet well-known. PATIENTS AND METHODS: The clinical manifestations, neuroradiological aspects and treatment of four patients suffering from hypertensive encephalopathy were studied; special attention was paid to manifestations presented by one patient which appeared representative of the usual manifestations of hypertensive encephalopathy. RESULTS: The main clinical features were visual disturbances (n = 4); altered consciousness (n = 2) and seizures (n = 3). Visual disturbances resulted from cortical lesions (n = 4) associated with optic nerve damage and retinopathy (n = 2). Cerebral imaging showed low density images (CT scan) and hypersignal (MRI, T2 sequence) located in parieto-occipital cortical ribbon and adjacent white matter from the first 24 hours following the onset of neurologic symptoms. In the studied patient, the abnormal images resolved within 1 month after the onset of the disease. Unilateral infarction of the anterior visual pathway affected two patients in whom: 1) hypertension remaining undetected for a long time was revealed by neurological signs; 2) visual impairment was preceded by an hypotensive episode induced by antihypertensive therapy. CONCLUSIONS: Neuroradiological features of hypertensive encephalopathy are useful in establishing the diagnosis. A gradual reduction of blood pressure could prevent the risk of visual complications.

Adolescent↗
PubMed1995

Extensive macrogyri or no visible gyri: distinct clinical, electroencephalographic, and genetic features according to different imaging patterns.

We studied 43 children with extensive brain gyral anomalies diagnosed radiologically and defined by (a) the absence or paucity of sulci over cortical areas affecting at least two lobes in each hemisphere, and (b) the absence or reduction of interdigitation between gray and white matter. We correlated the clinical, EEG, and genetic findings with the imaging features. A seemingly homogeneous group of patients (group A, n = 30) presented a common imaging pattern characterized by four features: (1) a thickened neocortex, (2) widened lateral ventricles, (3) apparent verticalization and widening of sylvian fissures, and (4) bilateral and symmetric distribution of the abnormalities. Another group of patients (group B, n = 13) exhibited heterogeneous imaging anomalies, termed "nonlissencephalic brain malformation," differing in at least one of the following four ways from the radiologic criteria defining group A: absence of verticalization of sylvian fissures (n = 12), thin neocortex (n = 2), normal-size lateral ventricles (n = 2), and asymmetric brain defects (n = 3). In group A, some clinical features had a significantly lower frequency (p < or = 0.01) than in group B: microcephaly, a complete lack of postural development, and intractable epilepsy. There was a significant relationship, but only in group A, between the degree of gyral anomalies and the extent of neurodevelopmental delay. Some EEG patterns (rapid rhythms and delta-theta rhythms) were highly specific for the group A patients. There was lower risk of familial recurrence in group A (recurrence of convolutional anomalies was 3.5% of sibship in group A versus 44% of sibship in group B, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Cortex↗
PubMed1995

[Angiokeratoma and fucosidosis. Immunohistochemical and ultrastructural study].

INTRODUCTION: Angiokeratoma can lead to diagnoses other than Fabry's disease. We report a case of angiokeratoma in a child with fucosidosis. CASE REPORT: A 7-year-old child with psychomotor retardation presented angiokeratoma located on the penis. Uptake of type I Ulex Europaeus Agglutinin antilectin antiserum was intense in the endothelial structure. This antibody is specific for alpha-L-fucose residues which were thus found in large quantities in the vacuoles of the ultrastructure. The patient also had a major deficiency in leukocyte, serum and fibroblast alpha-fucosidase. COMMENTS: This is a typical case of fucosidosis, a rare hereditary disease with autosomal recessive transmission due to generalized deficiency in alpha-L-fucosidase. Diffuse angiokeratosis should suggest, other than Fabry's disease, fucosidase and other enzyme deficiencies including sialidase, GM1 gangliosidase as well as Kanzaki's disease.

Angiokeratoma↗
PubMed1994

Submicroscopic deletions of 17p13.3 in type 1 Lissencephaly.

DNA markers YNZ22.1 and YNH37.3 were studied by Southern blotting in 14 patients with typical (11 cases) and atypical (3 cases) type 1 Lissencephaly, all with normal high resolution karyotype. A submicroscopic deletion was found in 2 typical cases: one with Miller-Dieker Syndrome (MDS), the other with Isolated Lissencephaly Sequence (ILS). These results suggest a genetic continuum between MDS and ILS. The low frequency of such deletions, especially in ILS, will necessitate direct testing of the newly identified LIS 1 gene.

Cerebral Cortex↗
PubMed1994

Refractory anaemia and mitochondrial cytopathy in childhood.

We report two cases of childhood myelodysplasia (MDS) related to a mitochondrial (mt) cytopathy that illustrate the difficulty in recognizing such disorders in patients with solely haematological signs. Both patients have refractory anaemia with ring sideroblasts and vacuolization of haemopoietic precursors. These cytological features are similar to those observed in Pearson's disease, recently identified as a mitochondrial disease, and are strongly suggestive of a mitochondrial enzyme defect. The diagnosis of mitochondrial cytopathy was established on Southern blotting of mt DNA, showing a mt DNA deletion, or on the impairment of the respiratory chain enzyme activities. The absence of cytogenic abnormalities, and the polyclonal pattern of peripheral neutrophil and lymphocyte fractions, suggest that, in mt cytopathies, MDS cannot be considered as a truly malignant disorder.

Anemia, Sideroblastic↗
PubMed1994

Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.

We report an inborn error of the tricarboxylic acid cycle, fumarase deficiency, in two siblings born to first cousin parents. They presented with progressive encephalopathy, dystonia, leucopenia, and neutropenia. Elevation of lactate in the cerebrospinal fluid and high fumarate excretion in the urine led us to investigate the activities of the respiratory chain and of the Krebs cycle, and to finally identify fumarase deficiency in these two children. The deficiency was profound and present in all tissues investigated, affecting the cytosolic and the mitochondrial fumarase isoenzymes to the same degree. Analysis of fumarase cDNA demonstrated that both patients were homozygous for a missense mutation, a G-955-->C transversion, predicting a Glu-319-->Gln substitution. This substitution occurred in a highly conserved region of the fumarase cDNA. Both parents exhibited half the expected fumarase activity in their lymphocytes and were found to be heterozygous for this substitution. The present study is to our knowledge the first molecular characterization of tricarboxylic acid deficiency, a rare inherited inborn error of metabolism in childhood.

Amino Acid Sequence↗
PubMed1994

[Syndrome of delayed maturation of the sucking-swallowing reflex].

BACKGROUND: Neonates with neurological diseases often have difficulty in sucking or swallowing. This report describes such difficulties in a group of infants with normal development, suggesting late maturation of sucking and swallowing. POPULATION AND METHODS: Seven infants (four girls, three boys) had suffered from aspiration since their first day of life (four cases) with severe asphyxia (two cases), late repeated episodes of airway obstruction by accumulated secretions (two cases), and weak isolated sucking and swallowing (one case). The lack of sucking and swallowing or difficulty with them were the main manifestations in these newborns: the face lacked expression and the tongue movements were abnormal with, in two cases, hyper-extension of the neck. A second phase during the first months of life was marked by episodes of bradycardia and/or drowsiness. A third phase during the first years of life was characterized by repeated episodes of respiratory infections, recurrent stridor and accumulation of saliva. These manifestations required prolonged hospitalization (mean: 2.5 months), nasogastric feeding, and in two cases, surgery. The investigations during the acute phases included a cineradiographic study of swallowing, laryngoscopy, monitoring of the distal esophagus pH, a barium swallow, polygraphic recording during sleep and MR imaging of the brain stem. The difficulties in sucking or swallowing disappeared before the age of 6 months (two cases), between 6 and 12 months (one case), between 1 and 5 years (four cases) without any sequelae or speech disorders. CONCLUSION: These transient sucking or swallowing difficulties suggest late maturation of praxis. They required specialized prolonged education after careful, essentially clinical, investigation.

Deglutition Disorders↗