Biomedical subjects

Jean Marie Saudubray

Publications and source records attributed to Jean Marie Saudubray.

5 recordsLinked to original sources

PubMed2006

Impact of inborn errors of metabolism on admission and mortality in a pediatric intensive care unit.

The authors conducted a retrospective analysis of the patients admitted to a pediatric intensive care unit (PICU) during a five-year period, with specific focus on those with a suspected or confirmed diagnosis of inborn errors of metabolism (IEM), in order to ascertain the resources required to care for these patients. Medical records were reviewed for all admissions between January 1998 and December 2002 in a single metabolic referral center, and a subset of patients were identified with suspected IEM at admission or diagnosed IEM at hospital discharge. These patient charts were then further reviewed and the following information was extracted: IEM diagnosis, demographic data, biochemical characteristics at admission, need for mechanical ventilation, use of extracorporeal removal therapy, and outcome at PICU discharge. The study population comprised 70 patients (2.2% of all admissions during the study period) and included 33 neonates and 37 children aged >28 days. IEM diagnosis was known at the time of admission to the PICU in 9/33 of the neonates and 23/37 of the older children. Forty-three of the patients required invasive mechanical ventilation, while continuous extracorporeal removal therapy was used in 27 children. The median length of PICU stay was 3 days (range, 1 to 13 days) and 20 patients (28.6%) died. In conclusion, these observations show that inherited metabolic disease may be as frequent a primary diagnosis as septic shock in some PICUs. In neonates, these diseases are not usually diagnosed prior to PICU admission. Patients with IEM admitted to a PICU require aggressive support (including mechanical ventilation and extracorporeal removal therapies), and consume significant resources for relatively short PICU stays. These patients constitute a significant diagnostic and therapeutic challenge for pediatric intensivists.

Child↗

PubMed2006

Mitochondrial respiratory chain deficiencies expressing the enzymatic deficiency in the hepatic tissue: a study of 31 patients.

We describe the clinical, biochemical, and molecular characteristics of 31 patients with hepatic respiratory chain deficiencies to suggest possible guidelines for a liver biopsy. Initially, 67% of the children did not have any sign of hepatic dysfunction, and 35% presented exclusively with neurologic symptoms. Initial hyperlactacidemia was severe in 52%. Mortality was high (52%) and more marked in newborns; 28% never developed hepatic disease over time despite long-term follow-up. Hepatic, nonspecific multisystem initial symptoms, and constant hyperlactacidemia had significant statistical value as negative prognosis factors. We conclude that liver biopsy should be considered not only in patients with hepatic involvement, but also in patients with predominant neurologic disorders if there is a suspicion of a mitochondrial respiratory chain defect.

Child, Preschool↗

PubMed2005

Kinetic modeling of plasma leucine levels during continuous venovenous extracorporeal removal therapy in neonates with maple syrup urine disease.

A kinetic modeling of leucine plasma concentration changes is proposed to describe the plasma leucine reduction rate during continuous extracorporeal removal therapy (CECRT) in neonates with maple syrup urine disease. Data were obtained from seven neonates using a bicompartmental model for the best fitted curve of plasma leucine decrease during CECRT. During the first 3 h, leucine plasma levels decreased according to an exponential curve: [Leu](t) = [Leu](i) x 0.95 x 10(-0.09t) where [Leu](t) is the leucine plasma level (mumol/L) at time t (h) during CECRT and [Leu](I) is the initial plasma level. From h 4 to the end of CECRT, a second exponential curve was observed: [Leu](t) = [Leu](i) x 0.74 x 10(-0.05t). Plasma leucine levels obtained from three other neonates were similar to those predicted by the model. The apparent distribution volumes for leucine that correspond to the two exponential equations obtained were calculated from the leucine mass removal collected in the spent dialysate and ultrafiltrate. The distribution volume was 34 +/- 3% of body weight during the first 3 h of CECRT and 72 +/- 7% from h 4 to the end of CECRT. These figures are similar to known values for the extracellular water compartment and for total body water in the newborn. The findings suggest that leucine handling during CECRT is similar to that of nonprotein-bound small-molecular-weight solutes such as urea.

Body Water↗

PubMed2003

A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis.

Mitochondrial respiratory chain complex III (ubiquinol-cytochrome c reductase) consists of 11 subunits, only one (cytochrome b) being encoded by the mitochondrial DNA. Disorders of complex III are comparatively rare but are nevertheless present as a clinically heterogeneous group of diseases. To date, no mutation in any of the nuclear-encoded subunits has been described. We report here a deletion in the nuclear gene UQCRB encoding the human ubiquinone-binding protein of complex III (QP-C subunit or subunit VII) in a consanguineous family with an isolated complex III defect. In the proband, a homozygous 4-bp deletion was identified at nucleotides 338-341 of the cDNA predicting both a change in the last seven amino acids and an addition of a stretch of 14 amino acids at the C-terminal end of the protein. Both parents were found to be heterozygous for the deletion, which was absent from 55 controls. Low temperature (-196 degrees C) spectral studies performed on isolated mitochondria from cultured skin fibroblast of the proband showed a decreased cytochrome b content suggestive of a role for the QP-C subunit in the assembly or maintenance of complex III structure.

Acidosis, Lactic↗

PubMed2002

Peroxisomal disorders.

Peroxisomes are subcellular organelles catalyzing a number of indispensable functions in cellular metabolism. The importance of peroxisomes is stressed by the existence of an expanding number of genetic diseases in which there is an impairment of one or more peroxisomal functions. The prototype of this group of diseases is the cerebro-hepato-renal syndrome of Zellweger (ZS), first described as a familial syndrome of multiple congenital defects in 1964. ZS is characterized by the presence of dysmorphias and polymalformative syndrome, severe neurologic abnormalities including neurosensory defects and hepato-intestinal dysfunction with failure to thrive and usually early death. Other peroxisomal disorders share some of these symptoms, but with varying degrees of organ involvement, severity of dysfunction and duration of survival. This paper provides an overview of the peroxisomal disorders including their clinical, biochemical and molecular characteristics with particular emphasis on the clinical presentation in neonates.

Diagnosis, Differential↗