Late diagnosis of 3ß-Hydroxysteroid dehydrogenase deficiency: the pivotal role of gas chromatography-mass spectrometry urinary steroid metabolome analysis and a novel homozygous nonsense mutation in the HSD3B2 gene.

OBJECTIVES: 3ß-Hydroxysteroid dehydrogenase (3ß-HSD) deficiency is a rare type of congenital adrenal hyperplasia caused by recessive loss-of-function mutations in HSD3B2 gene. CASE PRESENTATION: We report an 8.5-year-old, 46XY, Roma boy with advanced adrenarche signs born to consanguineous parents. He was born at term with ambiguous genitalia. At 15 days of age, he underwent replacement therapy with hydrocortisone and fludrocortisone due to a salt wasting (SW) crisis and adrenal insufficiency. At 3.5 years, he was admitted again with SW crisis attributed to the low - unadjusted to body surface area - hydrocortisone dose and presented with bilateral gynecomastia and adrenarche. At 8.5 years, his bone age was four years more advanced than his chronological age and he was prepubertal, with very high testosterone levels. Gas chromatography-mass spectrometry (GC-MS) urinary steroid metabolome analysis revealed the typical steroid metabolic fingerprint of 3ß-HSD deficiency. Sequencing of the HSD3B2 gene identified in homozygosity the novel p.Lys36Ter nonsense mutation. Furthermore, this patient was found to be heterozygous for p.Val281Leu in the CYP21A2 gene. Both parents were identified as carriers of the p.Lys36Ter in HSD3B2. CONCLUSIONS: A novel nonsense p.Lys36Ter mutation in HSD3B2 was identified in a male patient with hypospadias. 3ß-HSD deficiency due to mutations in the HSD3B2 gene is extremely rare and the finding of a patient with this rare type of disorders of sex development (DSD) is one of the very few reported to date. The complexity of such diseases requires a multidisciplinary team approach regarding the diagnosis and follow-up.

[Nuclear medicine applications of the gastrointestinal tract in pediatric surgery].

There are pathological entities of the gastrointestinal tract whose investigation and follow-up remain quite challenging for pediatric surgeons. Although there are many new diagnostic techniques, radionuclide applications still remain important. Nuclear medicine plays a crucial role in diagnosis of biliary atresia and contributes to its differential diagnosis from neonatal hepatitis with an accuracy of 95% through cholescintigraphy. This method also detects postoperative complications, such as bile leaks and obstruction after liver transplantation in children. Technetium-99m pertechnetate scan is considered the standard method for preoperative diagnosis of a Meckel's diverticulum, characterized by a specificity of 95% and a sensitivity of 85%. Milk scan is the most sensitive noninvasive method for detecting gastroesophageal reflux, due to its high temporal acquisition rate and reveals tracheoesophageal communications in neonates suffering from persistent cough and recurrent pulmonary infections. Finally, in case of necrotizing enterocolitis, Nuclear Medicine has to offer the measurement by radioimmunological methods of markers such as IL-6, T- antigen, I-FABP, glutathione S-transferase and ß-galactocidase of intestinal mucosa cells, which are useful in the diagnosis, follow-up and prognosis of the disease. In conclusion, radionuclide techniques in the investigation of the gastrointestinal tract in neonates and children are useful functional methods, with lower radiation exposure compared to radiological techniques that are usually applied.