Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients.

CONTEXT: In 46,XY disorders of sex development, 5α-reductase deficiency is rare and is not usually the first-intention diagnosis in newborn ambiguous genitalia, contrary to partial androgen insensitivity syndrome. Yet the cause of ambiguous genitalia may guide sex assignment, and rapid, precise diagnosis of 5α-reductase deficiency is essential. OBJECTIVE: The aim of the study was to describe relevant data for clinical diagnosis, biological investigation, and molecular determination from 55 patients with srd5A2 mutations identified in our laboratory over 20 yr to improve early diagnosis. SETTING: The study was performed at Montpellier University Hospital. PATIENTS: We studied a cohort of 55 patients with srd5A2 gene mutations. MAIN OUTCOME MEASURE(S): Genetic analysis of srd5A2 was conducted. RESULTS: Clitoromegaly (49.1%) and microphallus with various degrees of hypospadias (32.7%) were frequent phenotypes. Female external genitalia (7.3%) and isolated micropenis (3.6%) were rare. Seventy-two percent of patients were initially assigned to female gender; five of them (12.5%) switched to male sex in peripuberty. Over 72% of patients were considered for 5α-reductase deficiency diagnosis when the testosterone/dihydrotestosterone cutoff was 10. In 55 patients (with 20 having a history of consanguinity), we identified 33 different mutations. Five have never been reported: p.G32S, p.Y91H, p.G104E, p.F223S, and c.461delT. Homozygous mutations were present in 69.1% of cases, compound heterozygous mutations in 25.5%, and compound heterozygous mutations alone with the V89L polymorphism in 5.4%. Exons 1 and 4 were most affected, with 35.8 and 21.7% mutant alleles per exon, respectively. CONCLUSIONS: In the largest cohort to date, we demonstrate a wide spectrum of phenotypes and biological profiles in patients with 5α-reductase deficiency, whatever their geographical or ethnic origins.

[Acute rheumatic fever is still active in Martinique. Epidemiological and clinical study of 34 cases observed during the 1987-1991 period]. / Le rhumatisme articulaire aigu toujours vivace en Martinqiue. Etude épidémiologique et clinique de 34 cas observés pendant la période 1987-1991.

The authors report 34 cases of acute rheumatic fever observed in children in the North-Atlantic region of the Martinique island during a 5 years period (1987-1991). The majority of the patients belong to areas with poor socio-economic conditions. Clinical manifestations are mainly polyarthritis, monoarthritis, and abdominal pain, associated with accelerated erythrocyte sedimentation rate and high antistreptolysin O titer. Carditis remains the most important complication, 14 out of 34 children being concerned. The prognosis is favorable in most cases, but four children have mitral valve insufficiency and two other have moderate aortic valve insufficiency as sequelae. Although there is a decline in the incidence of the disease in comparison to previous years, the same endemic area is found in this study. Explanations of this phenomenon and recommendations for a new eradication campaign are discussed.

[Acute pancreatitis and valproic acid]. / Pancréatite aiguë et acide valproïque.

An 11 year-old epileptic boy, treated with valproic acid developed after 11 months on therapy a severe acute pancreatitis. Pancreatitis recurred 18 months after re-exposure to the same drug. Twenty-four cases of valproic-acid induced acute pancreatitis have been reported in the literature. However, it remains a major anticonvulsant drug whose tolerance is usually excellent. This complication, although exceptional needs to be known so that the treatment can be stopped in due-time if not tolerated or to avoid eventual recurrence.