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.

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Congenital generalized hypertrichosis, in its most common form, is idiopathic. In the absence of underlying endocrine or metabolic disorders, congenital generalized hypertrichosis is rare in humans, affecting as few as one in a billion individuals and may be an isolated condition of the skin, or a component feature of other disorders or syndromes. Congenital generalized hypertrichosis terminalis is an extremely rare condition, a distinct subset of disorders with congenital hypertrichosis, presenting with excessive hair as the primary clinical feature. Congenital generalized hypertrichosis terminalis is characterized by universal excessive growth of pigmented terminal hair and often accompanied with gingival hyperplasia and/or a coarse face. Gingival hyperplasia may be delayed even until puberty. Its pathogenesis may be caused by one of the following mechanisms: conversion of vellus to terminal hairs and/or prolonged anagenetic stage, and/or increase in the number of hair follicles. Since the Middle Ages, less than 60 individuals with congenital hypertrichosis terminalis have been described, and, according to the most recent estimates, less than 40 cases were documented adequately and defi nitively in the literature. Recent articles identifi ed congenital generalized hypertrichosis terminalis as a genomic disorder. This report is a follow up of a six-year-old boy born from the fi rst normal pregnancy of non-consanguineous parents, starting from delivery. Our investigation revealed a history of: excessive hair growth and a coarse face from birth; increased body weight with high blood pressure and gingival hyperplasia at the age of four months. The parents denied any medication or chemical intake during pregnancy, as well as a history of hypertrichosis in their families. The child had a congenital hydronephrosis of the right kidney. Ultrasound and magnetic resonance imaging revealed severe congenital hydronephrosis of the right kidney and suspicion of hypertrophy of the left adrenal gland suggestive of an adenoma. The follow up showed normal values of hormones which excluded adrenal tumor. At the age of 8 months the patient underwent right-sided nephrectomy after several urinary infections. The child was admitted again to our Clinic at the age of four years, with generalized hypertrichosis, gingival hyperplasia and a coarse face without any other pathological signs. He has had a normal intellectual development, but was extremely shy, unconfi dent and dependent on his mother. The relevant laboratory investigations showed normal full blood count, biochemical, hormonal test results and normal function of the single kidney. Molecular chromosome analysis revealed heterozygous deletion on chromosome 17q12 region. Prolonged follow-up with routine checkups every 6-12 months was advised, including regular outpatient appointments particularly with an endocrinologist, because of the risk of diabetes mellitus, and with a nephrologist, for control of renal function. Laser hair removal was suggested and the patient under...

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.

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