First results of the growth disorders related twinning programme Partners4Growth implemented at the tertiary university pediatric endocrinology clinics in Bulgaria.

OBJECTIVES: Early diagnosis of childhood growth disorders, their timely and proper treatment are important for better outcomes.The aim of the present study was to assess the results of the first 18 months of the growth disorders related twinning programme "Partners4Growth" implemented at all tertiary university pediatric endocrinology clinics in Bulgaria. METHODS: In 2019, Partners4Growth started operation at 7 centres (4 experienced and 3 twin centres) with the main aim of aligning their practices in the shortest possible time. Education of twin centres' personnel was organized, equipment and methods for growth evaluation and follow-up were standardized. The approach was tested initially at one centre. At baseline and at the 18th month a questionnaire concerning diagnosis and management of recombinant human growth hormone (rhGH) requiring disorders was applied. RESULTS: A total of 104 new patients were diagnosed compared to 30 in the previous year. Of those, 91 started rhGH treatment - 65 (64 %) GH deficient, 12 (12 %) Turner syndrome, 7 (7 %) Prader-Willi syndrome patients, and 7 (7 %) born small for gestational age without postnatal catch-up, representing 35.8 % of all currently rhGH treated Bulgarian children. A better geographical coverage and more advanced diagnostic and management practices were achieved. CONCLUSIONS: Partners4Growth facilitated the alignment of the tertiary pediatric endocrinology centres competences thus leading to an improved diagnosis and treatment of growth disorders as well as better patients' access. For its short existence, the Programme increased significantly the number of new patients in the difficult times of COVID-19 pandemic thus justifying its continuation.

New Territory for an Old Disease: 5-Alpha-Reductase Type 2 Deficiency in Bulgaria.

Disorders/differences of sexual development (DSD) are a group of conditions, some of which can be clinically indistinguishable mainly due to their phenotypic variability. Defining the molecular basis of their wide spectrum is still in progress. The diagnosis of 5-alpha-reductase type 2 (5α-reductase-2) deficiency is difficult especially in newborns and pre-pubertal individuals, and as a result its frequency might be underestimated. In the present study, we describe the clinical characteristics and molecular defects in 3 nonrelated 5α-reductase-2 deficiency patients of Bulgarian descent. Sequencing analysis revealed the mutations p.Y188CfsX9 and p.G196S, and MLPA analysis showed a deletion of exon 1 in the SRD5A2 gene. The observed genetic substitutions were not detected in 76 additionally screened unrelated controls, but a heterozygous healthy carrier of the p.R171S mutation was found. This is the first study on the molecular basis of 5α-reductase-2 deficiency in Bulgaria. It suggests that the carrier frequency of mutations in the SRD5A2 gene might be noteworthy worldwide. There is no correlation between cultural aspects, location, and/or population size and the number of different mutations in SRD5A2 detected, and more efforts should be made to determine the prevalence of this condition in different geographic areas. Our study supports the importance of genetic testing in 46,XY DSD patients, especially in countries or regions where 5α-reductase-2 deficiency has not been reported so far.

Males with Paternally Inherited MKRN3 Mutations May Be Asymptomatic.

Ten girls with sporadic central precocious puberty were screened for mutations in the maternally imprinted gene MKRN3. We detected 1 novel frameshift mutation (p.Arg351Serfs*44) and a previously described mutation (p.Pro161Argfs*10). In the course of investigating the family, genetic analysis found 2 asymptomatic males with paternally inherited MKRN3 mutations, which has not been reported in previous studies.