ABSTRACT
3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic disorder due to a deficiency of the 3-hydroxy-3-methylglutarylCoA lyase (HMG-CoA lyase), a mitochondrial enzyme involved in ketogenesis and in the final step of l-leucine catabolism. HMG-CoA lyase deficiency can lead, in particular circumstances, such as fever, prolonged fasting or digestive disorders, to brutal and severe hypoglycemia with metabolic acidosis and sometimes fatal coma. We report on a new case of 3-hydroxy-3-methylglutaric aciduria particular by its late onset in a 3-year-old patient. Molecular investigation identified two new sequence modifications in the HMGCL gene: c.494G>A (p.Arg165Gln) and c.820G>A (p.Gly274Arg). We remind about this case report that the therapeutical is mainly preventive and allows a very good prognosis for this disease. Long-term treatment consists in limited fasting time, continuous low protein diet and l-carnitine supplementation. Preventive measures are essential: prevention of fasting and emergency treatment during intercurrent infections.
Subject(s)
Amino Acid Metabolism, Inborn Errors/genetics , Chromosome Aberrations , Genes, Recessive/genetics , Hypoglycemia/genetics , Meglutol/urine , Oxo-Acid-Lyases/deficiency , Oxo-Acid-Lyases/genetics , Rare Diseases/diagnosis , Rare Diseases/genetics , Alleles , Amino Acid Metabolism, Inborn Errors/diagnosis , Carnitine/administration & dosage , Child, Preschool , Combined Modality Therapy , DNA Mutational Analysis , Diet, Protein-Restricted , Exons/genetics , Humans , Hypoglycemia/urine , Leucine/metabolism , Male , Polymerase Chain Reaction , Rare Diseases/therapy , Sequence Analysis, DNAABSTRACT
AIM: To determine the impact of rapid influenza test (RIT) on the prescription of additional tests, antibiotics and oseltamivir, and the influence of oseltamivir on clinical signs and parents' day work stoppage. METHODS: Prospective study in the pediatric emergency department of Nice University Hospital from 29th January 2007 to 3rd March 2007 including children from 1 month to 6 years old with fever greater or equal to 38.5 degrees C for less than 48 h. Virologic research on nasopharyngeal aspiration was: immunofluorescence, cell culture and RIT Quickvue. Clinical informations, additional tests and treatments were registered for each child. An antiviral treatment (oseltamivir) was proposed to children older than 1 year with positive RIT. Evolution at 7 days was evaluated by phone contact. RESULTS: One hundred and seventy-seven children were included (mean age 24 months, sex-ratio 1.88). The RIT was positive in 42.3% (n=75). Compared with cell culture, the sensibility, specificity, positive predictive value and negative predictive value of the RIT were, respectively, 95.6, 91.6, 88 and 97%. Clinical signs significantly correlated to influenza were: impairment, rhinitis and acute otitis media. In the RIT positive group, there were significantly less additional tests (13 versus 36) and particularly urinalysis (5 versus 19), and more spreading in the family (p=0.0002). There was not any significant difference concerning hospitalizations, antibiotic prescriptions, or parents' day work stoppage. CONCLUSION: During influenza epidemic, in a pediatric emergency department, RIT allows a reduction of additional tests in febrile young children, particularly urinalysis.