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Biomedical subjects

G Touati

Publications and source records attributed to G Touati.

At least 19 recordsLinked to original sources
PubMed2005

[Congenital hyperinsulinism in newborn and infant].

Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in early infancy. The inappropriate oversecretion of insulin is responsible for profound hypoglycaemias requiring aggressive treatment to prevent severe and irreversible brain damage. Several classifications of HI can be attempted, based on: 1) the onset of hypoglycemia in the neonatal period or later in infancy; 2) the histological lesion: focal or diffuse; 3) the genetic transmission: sporadic, recessive, or less frequently dominant. The most common underlying mechanism of HI is dysfunction of the pancreatic ATP-sensitive potassium channel (K(+)(ATP)). The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region. Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion. Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous. The distinction between the focal and the diffuse HI is very important, because the treatments are different. To distinguish between focal and diffuse HI, transhepatic catheterisation with pancreatic venous sampling was the reference technique, but will likely be replaced by [(18)F] Fluoro-L-Dopa PET scan, which is easier to perform. In absence of response to the medical treatment (diazoxide) a limited pancreatectomy permits to cure focal HI, while a diffuse HI requires a subtotal pancreatectomy with high risk of subsequent diabetes mellitus.

ATP-Binding Cassette Transporters↗
PubMed2005

Congenital hyperinsulinism and mosaic abnormalities of the ploidy.

BACKGROUND: Congenital hyperinsulinism and Beckwith-Wiedemann syndrome both lead to beta islet hyperplasia and neonatal hypoglycaemia. They may be related to complex genetic/epigenetic abnormalities of the imprinted 11p15 region. The possibility of common pathophysiological determinants has not been thoroughly investigated. OBJECTIVE: To report abnormalities of the ploidy in two unrelated patients with congenital hyperinsulinism. METHODS: Two patients with severe congenital hyperinsulinism, one overlapping with Beckwith-Wiedemann syndrome, had pancreatic histology, ex vivo potassium channel electrophysiological studies, and mutation detection of the encoding genes. The parental genetic contribution was explored using genome-wide polymorphism, fluorescent in situ hybridisation (FISH), and blood group typing studies. RESULTS: Histological findings diverged from those described in focal congenital hyperinsulinism or Beckwith-Wiedemann syndrome. No potassium channel dysfunction and no mutation of its encoding genes (SUR1, KIR6.2) were detected. In patient 1 with congenital hyperinsulinism and Beckwith-Wiedemann syndrome, paternal isodisomy for the whole haploid set was homogeneous in the pancreatic lesion, and mosaic in the leucocytes and skin fibroblasts (hemihypertrophic segment). Blood group typing confirmed the presence of two erythroid populations (bi-parental v paternal only contribution). Patient 2 had two pancreatic lesions, both revealing triploidy with paternal heterodisomy. Karyotype and FISH analyses done on the fibroblasts and leucocytes of both patients were unremarkable (diploidy). CONCLUSIONS: Diploid (biparental/paternal-only) mosaicism and diploid/triploid mosaicism were present in two distinct patients with congenital hyperinsulinism. These chromosomal abnormalities led to paternal disomy for the whole haploid set in pancreatic lesions (with isodisomy or heterodisomy), thereby extending the range and complexity of the mechanisms underlying congenital hyperinsulinism, associated or not with Beckwith-Wiedemann syndrome.

Chromosome Aberrations↗
PubMed2005

Urea cycle defects: management and outcome.

This paper reviews the clinical presentation of 217 patients with urea cycle defects, including 121 patients with neonatal-onset forms and 96 patients with late-onset forms. Long-term outcome of these patients is also reported with the severity of the neonatal forms of these disorders, mostly for ornithine carbamoyltransferase-deficient males. Patients with late-onset forms may present at any age and carry a 28% mortality rate and a subsequent risk of subsequent disabilities.

Adolescent↗
PubMed2005

Severe hypoglycaemia in isolated 3-methylcrotonyl-CoA carboxylase deficiency; a rare, severe clinical presentation.

Since the introduction of neonatal screening for branched-chain organic acidurias, it has been noted that isolated 3-methylcrotonyl-CoA carboxylase deficiency is probably one of the most frequent organic acidurias. Only a few cases with severe clinical presentation have been described. Profound hypoglycaemia is an uncommon but life-threatening complication.

Carbon-Carbon Ligases↗
PubMed2005

Methylmalonic and propionic acidaemias: management and outcome.

Organic acidurias comprise many various disorders. Methylmalonic aciduria (MMA) and propionic aciduria (PA) are the most frequent diseases and the two organic acidurias for which we have better knowledge of the long-term outcome. Comparing the outcome of patients born before and after 1990, it appears that better neonatal and long-term management have improved the survival rate. Less than 20% of the patients died in either the neonatal period or before the age of 10 years. However, most surviving patients showed poor nutritional status with growth retardation and about 40% present some kind of visceral or neurological impairment. The developmental outcome may have improved in MMA patients, with IQ higher than 75 in about 40% patients aged more than 4 years. Conversely, poor intellectual development is the rule in PA patterns, with 60% having an IQ less than 75 and requiring special education. Successful liver and/or renal transplantations, in a few patients, have resulted in better quality of life but have not necessarily prevented neurological and various visceral complications. These results emphasize the need for permanent metabolic follow-up whatever the therapeutic strategy.

Child, Preschool↗
PubMed2005

Dominantly inherited hyperinsulinaemic hypoglycaemia.

Congenital hyperinsulinism (HI), the most important cause of hypoglycaemia in early infancy, is a heterogeneous disease with two types of histological lesions, focal and diffuse, with major consequences in terms of surgical approaches. In contrast to focal islet-cell hyperplasia, always sporadic to our knowledge, diffuse hyperinsulinism is a heterogeneous disorder involving several genes, various mechanisms of pathogenic mutations and different transmissions: (i) channelopathy involving the genes encoding the sulphonylurea receptor (SUR1) or the inward-rectifying potassium channel (Kir6.2) in recessively inherited HI or more rarely dominantly inherited HI; (ii) metabolic disorders implicating the short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) enzyme inrecessively inherited HI, the glucokinase gene (GK), the glutamate dehydrogenase gene (GLUD1) when hyperammonemia is associated, dominant exercise-induced HI with still-unknown mechanism, and more recently the human insulin receptor gene in dominantly inherited hyperinsulinism. Thus, dominant HI disorders always correspond to diffuse HI, where most hypoglycaemia occur in infancy, and are sensitive to medical treatment. Channel causes could be due to dominant negative mutation with one abnormality in channels composed of four Kir6.2 subunits and four SUR1 subunits, leading to a complete destruction of the channel structure or function, or due to haploinsufficiency with only one functional allele, leading to 50% of functional protein, which is not sufficient to obtain enough opened channels to maintain the membrane depolarized. Metabolic causes are due to a gain of function of enzyme activity (deregulated enzymes), except for physical exercise-induced hyperinsulinaemic hypoglycaemia, of still-unknown cause. Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in early infancy (Aynsley-Green et al 2000; Cornblath et al 1990; Pagliara et al 1973; Thomas et al 1977). The inappropriate oversecretion of insulin is responsible for profound hypoglycaemia that requires aggressive treatment to prevent severe and irreversible brain damage (Volpe 1995). HI is a heterogeneous disease associated with several genes, various mechanisms of pathogenic mutations and different transmissions (Dunne et al 2004).

Exercise↗
PubMed2005

[Hypoglycemia associated with oral sulfonylurea hypoglycaemic agents in an 11-year-old girl].

UNLABELLED: In children more than 8 years old, hyperinsulinism is the most common cause of hypoglycemia. CASE REPORT: We report the case of an 11-year-old girl who presented recurrent hypoglycemia with endogenous hyperinsulinism (high insulin and C-peptide concentrations). The morphological investigations didn't find insulinoma. Finally the questioning identifies the voluntary intoxication with hypoglycemic agent. At a later date, the sulfonylurea dosage during an hypoglycaemic episode was positive. CONCLUSION: The sulfonylurea drugs can mimic an endogenous hyperinsulinism and mislead the diagnostic to an insulinoma suspicion and lead to a surgical exploration. A sulfonylurea dosage should be done before planning out surgery.

Child↗
PubMed2005

Long-term follow-up of neonatal mitochondrial cytopathies: a study of 57 patients.

OBJECTIVES: We sought to determine the long-term clinical and biochemical outcome of newborns with mitochondrial cytopathies (MCs) and to identify possible prognostic factors that may modify the course of these diseases. MATERIAL AND METHODS: Fifty-seven newborns with MCs were identified in a retrospective review (1983-2002). We defined 2 different outcome categories: clinical (neurologic, hepatic, myopathic, and multiorganic) and biochemical (lactate level normalization or initially normal remaining unchanged, decreased but not normalized, and persistently high). We used 2 different statistical approaches: (1) survival studies depending on the initial symptoms and lactate and enzymatic deficiencies using the Kaplan-Meier method; and (2) the same variables compared with different survival age groups and clinical and biochemical outcome categories using the chi2 test. RESULTS: Thirty-three patients died (57.8%), 12 remain alive (21%), and 12 were lost in the follow-up; 6 of them are currently older than 4 years. Most of the patients manifested multiorganic disease (64.8%) and high lactate level (77.1%) over time. Children surviving to 2.5 to 3 years of age were more likely to survive for a long period of time. Initial neurologic and hepatic presentation increased the risk to develop neurologic disease and severe persistent hyperlactacidemia, respectively. Initial severe hyperlactacidemia and combined enzyme deficiencies were significant risk factors for higher mortality and multiorganic disorders. Two patients with exclusively myopathic outcome are alive and cognitively normal at 12 years of life. CONCLUSIONS: Children with neonatal-onset MCs have very high mortality and poor prospects. However, some with life-threatening presentations may gradually improve, giving rise to less severe diseases. Those with exclusively myopathic symptoms have a better prognosis.

Child, Preschool↗
PubMed2004

[Aortobronchial fistulas].

INTRODUCTION: Aortobronchial fistulas are uncommon but generally fatal if not treated surgically. Haemoptysis is the main symptom of this pathology. STATES OF ART AND PERSPECTIVES: Aortobronchial fistulas occur most commonly in patients with thoracic aneurysms (atherosclerosis, mycotic, aortic surgery's complication...). Main investigation is CT angiography with 2 D and 3 D reconstructions. CONCLUSION: Endovascular exclusion can be efficient treatment option.

Aortic Diseases↗
PubMed2003

Comparative histological and biometric study of the coronary, radial and left internal thoracic arteries.

In an attempt to elucidate the causes of occlusion of radial arteries used for coronary artery bypass grafts and to improve the results of these procedures, we studied the biometry and histology of the coronary, radial and left internal thoracic arteries. These arteries were harvested from 20 cadavers (13 males, 7 females). The specimens were calibrated to the various bypass graft sites using coronary calibrators, and were then submitted to histological examination to determine the structure and innervation of the vessel wall. No correlation was observed between the internal calibers of these various arteries, with the exception of the anterior interventricular and right coronary arteries. Intimal changes and the presence of atheromatous plaque were observed in coronary and radial arteries, but never in the internal thoracic artery. Like the coronary arteries and their branches, the radial artery is a muscular artery. Aging of muscular arteries results in thickening of the intima, which becomes fibrotic due to migration of myocytes from the media and duplication of the internal elastic lamina. The media becomes fibrous, hypertrophic or atrophic. The walls of the radial and coronary arteries contain several adventitial nerves (sympathetic and parasympathetic nerve fibers), but these nerve fibers were not observed in the wall of the left internal thoracic artery. In contrast, the internal thoracic artery, like the aorta, is an elastic artery. Aging of elastic arteries is first observed between the ages of 20 and 29 years and is characterized by loss of one or several elastic laminae of the media and more marked intimal thickening, over a variable length. Even if a radial artery's caliber is similar to that of the coronary artery, histological evolution and graft patency depend on its muscular identity.

Aged↗
PubMed2003

[Aortobronchial fistula developing from an infectious aneurysm of the thoracic aorta].

Aortobronchial fistula presenting as massive haemoptysis is a rapidly fatal process if not promptly diagnosed and repaired. It's an unusual complication of thoracic aneurysm. We report the case of a 61-year-old woman with rupture of a thoracic aortic infectious aneurysm secondary to an Escherichia coli infection. Aortobronchial fistula diagnosis should be considered in patients who have minor or major haemoptysis and correct diagnostic procedures should be performed early. An aggressive surgical approach is often necessary.

Anti-Bacterial Agents↗
PubMed2003

Intimo-intimal intussusception: a rare clinical form of aortic dissection.

A 33-year-old hypertensive man presented with epigastric pain radiating to the back. Transoesophageal echocardiography (TOE) revealed an intimal flap on the aortic arch and descending aorta. No intimal flap of the ascending aorta was detected on TOE or CT. The diagnosis was made on opening the ascending aorta: complete circumferential dissection of the ascending aorta flush with the coronary ostia, with no residual intimal flap, and intimo-intimal glove-finger intussusception of the internal channel into the descending thoracic aorta. Aortic intussusception is a very rare form of Type I dissection, and the absence of intimal tear in the ascending aorta can be misleading and delay the diagnosis.

Adult↗
PubMed2003

Impaired mitochondrial pyruvate importation in a patient and a fetus at risk.

The patient was the first child of healthy consanguineous parents. She presented at birth with hypotonia, mild facial dysmorphism, periventricular cysts, marked metabolic acidosis, hyperlactacidemia with normal lactate/pyruvate molar ratios, normoglycemia, and normal ammonia. Hyperlactacidemia was severe (5-14 mmol/l) and not corrected with bicarbonate, thiamine (10 mg/d), 2-chloropropionate (100 mg/kg/d) and a ketogenic diet. Pyruvate dehydrogenase (PDHC) activity was normal in lymphocytes and fibroblasts. Functional assays were performed in digitonin-permeabilized fibroblasts to measure oxidation rates from radiolabeled pyruvate and malate. The production of [14C]acetylcarnitine or [14C]citric cycle intermediates derived from [2-14C]pyruvate as well as the release of 14CO(2) from [1-14C]pyruvate was severely impaired, whereas decarboxylation of [U-14C]malate was normal. With increasing concentrations of [1-14C]pyruvate, the patient's fibroblasts behave like control fibroblasts incubated in the presence of alpha-cyano-4-hydroxycinnamate, a specific inhibitor of mitochondrial pyruvate uptake: a progressive increase in 14CO(2) production was observed, likely due to passive diffusion of [1-14C]pyruvate through the mitochondrial membranes. Our results are consistent with a defect of mitochondrial pyruvate transport in the patient. Mutational analysis was precluded as the cDNA sequence of the pyruvate carrier has not been identified as yet in any organism. An affected fetus was recognized in a subsequent dichorionic twin pregnancy using the coupled assay measuring [2-14C]pyruvate oxidation rates on digitonin-permeabilized trophoblasts. After selective feticide, the pregnancy was uncomplicated with delivery at 37w of a healthy female, who is currently 2-month old.

Algeria↗
PubMed2003

[Biometry and structure of the left internal thoracic and radial coronary arteries].

In an attempt to elucidate the causes of occlusion of radial arteries for coronary artery bypass grafts, we studied the biometry and histology of the coronary, radial and left internal thoracic arteries of 20 anatomical subjects (13 males and 7 females). These specimens were calibrated to the various bypass graft sites using coronary calibrators, and were then submitted to histological examination to determine the structure of the vessel wall. Our preliminary results show no correlation between the internal calibres of these various arteries. Like the coronary arteries and their branches, the radial artery is a muscular artery. In contrast, the left internal thoracic artery like the aorta, is an elastic artery.

Aged↗
PubMed2002

[Hematologic manifestations of inborn errors of metabolism].

Haematological symptoms can be helpful for the diagnosis of metabolic diseases. A megaloblastic anemia orientates to folate and cobalamine anomalies when associated with homocystinemia and decreased plasma methionine levels, or to congenital oroticuria (hypochromia), Pearson syndrome (sideroblasts and vacuolisation of precursors) and thiamine transporter abnormality (sideroblasts) in the absence of homocystinuria. An hemolytic anemia orientates to anomalies of anaerobic glycolysis, heme synthesis, or iron metabolism, and Wilson disease. A pancytopenia orientates to organic aciduria, lysinuric protein intolerance, mevalonic aciduria and lysosomal storage diseases (Gaucher, Niemann Pick, Wolman) when hepatosplenomegaly is present. Uremic hemolytic syndrome and hemophagocytic lymphohistiocytosis respectively orientate to B12 anomalies, lysinuric protein intolerance, lysosomal storage diseases and organic aciduria.

Child↗
PubMed2002

Clinical approach to inherited metabolic disorders in neonates: an overview.

There are almost one hundred inborn errors of metabolism which can start in the neonatal period, but less than 20 are amenable to treatment. In general, an extremely evocative clinical setting is the course of a full-term baby born after normal pregnancy and delivery who, after an initial symptom-free period deteriorates relentlessly for no apparent reason and does not respond to symptomatic therapy. Investigations routinely performed in all sick neonates yield normal results. Emergency treatment must be undertaken in parallel with investigations. Five main presentations can be observed: a neurologic deterioration 'intoxication' type mostly suggests maple syrup urine disease, methylmalonic, propionic, isovaleric acidaemias and urea cycle disorders. Isolated seizures is the revealing symptom of pyridoxine-responsive and folinic acid responsive seizures. A jaundice or a liver failure suggest galactosaemia, fructosaemia, tyrosinaemia type I (after 3 weeks), phosphomannoisomerase deficiency or bile acid synthesis defects. Cardiac failure and heartbeat disorders should first suggest mitochondrial fatty acid oxidation (FAO) disorders. Persistent hypoglycaemia is the presenting sign of glyco/gluconeogeneis defects, hyperinsulinism and FAO disorders. The first line investigation relies upon the collection at the same time of a few samples including blood gases electrolytes, prothrombin time, transaminases, ammonia and lactic acid, and the search for ketonuria. The storage of plasma, urine and blood (on filter paper) is an important element in the diagnosis. The utilization of these samples should be carefully planned after taking advice from specialists in inborn errors.

Diagnosis, Differential↗
PubMed2002

Growth in paediatric Crohn's disease.

Growth failure (GF) is one of the major complications affecting children with inflammatory bowel disease. The faltering is temporary in 40-50% of cases and prolonged in 10-20% in Crohn's disease (CD). Such failure is rare in children with ulcerative colitis (5%). This complication is often associated with retarded bone development and delayed onset of sexual maturation. The delayed linear growth has a variety of causes including insufficient intake due to anorexia and the inflammatory process with increased energy and protein expenditure. Other factors are increased intestinal loss, secondary hypopituitarism and treatment with steroids. Therapeutic strategies of CD in children have changed this last decade by introducing new therapeutic agents such as topic steroids, immunosuppressors, anti-TNF (antibody and notably in children enteral nutrition which has shown its efficacy in inducing remissions of active CD, restoring nutritional status and stimulation of linear growth. The results of a recent prospective multicentric study over 2 years in 82 CD show that severe GF (-2 SD) is initially present in 15% (n = 12), among them 11 remain < -2SD after 2 years of follow-up. Six patients who were on the normal range initially increased their GF during the follow-up (< -2SD) (total 21% < -2SD (n = 17) at 2 years). At inclusion in this group there was no difference in growth velocity, used of steroids, enteral nutrition or severity of CD as compared to the group with no GF. It suggests that new treatment strategy should be developed in the future for this specific complication of paediatric CD.

Adrenal Cortex Hormones↗