Early and late diagnoses of 17ß-Hydroxysteroid dehydrogenase type-3 deficiency in two unrelated patients.

17ß-hydroxysteroid dehydrogenase type 3 deficiency is a rare cause of 46 XY disorders of sexual development. Mutations in the HSD17B3 gene result in reduced activity of the 17ß-HSD3 enzyme, decreasing the conversion of androstenedione to testosterone. In this report, two cases, admitted with different clinical findings in the neonatal and adolescent periods and were decided to be raised in different genders are presented. The first case who had complete female external genitalia presented on the third postnatal day with the complaint of swelling in the groin. He was decided to be raised as a male and was treated successfully with parenteral testosterone in order to increase phallus size before surgical correction of the external genitalia. The second case was an adolescent girl who presented due to pubertal virilisation and primary amenorrhoea and chose female gender. Molecular genetic analyses of the HSD17B3 gene revealed two different previously reported homozygous variants. We emphasise that patients with 17ß-hydroxysteroid dehydrogenase type 3 deficiency can present with heterogeneous clinical findings in different age groups. Early diagnosis is important to prevent future gender confusion and related problems.

Can ocular changes be detected early in children and adolescents with type 1 diabetes mellitus without retinopathy by using optical biometry and optical coherence tomography?

PURPOSE: To determine early ocular changes in children and adolescents with type 1 diabetes mellitus without retinopathy (T1DM-woR) by optical biometry (OB) and optical coherence tomography (OCT). METHODS: Seventy children and adolescents with T1DM-woR (patient group) and 72 healthy children and adolescents (control group) were included. Demographic data, anthropometric measurements and anterior-posterior segment parameters of groups were compared. Correlations between ocular parameters and glycosylated hemoglobin (HbA1c) level, age at diabetes mellitus (DM) onset and DM duration were evaluated. RESULTS: Patients with T1DM-woR had significantly shallower anterior chambers (3.50 ± 0.12 vs 3.67 ± 0.11 mm, p < 0.001), thicker lenses (3.65 ± 0.15 vs 3.37 ± 0.14 mm, p < 0.001), thinner central retinal nerve fiber layer (RNFL) thicknesses (95.3 ± 6.7 vs 104.8 ± 6.2 µm, p < 0.001) and thinner central choroidal thicknesses (292.8 ± 23.6 vs 325.1 ± 24.7 µm, p < 0.001) than healthy individuals. As the lens thickness (LT) increased, anterior chamber depth (ACD) decreased in patient group (r = - 0.368, p = 0.040). Other anterior (central corneal thickness, axial length, keratometry, spherical equivalent) and posterior (superior temporal, superior nasal, nasal, inferior nasal, inferior temporal, temporal RNFL thicknesses; nasal and temporal choroidal thicknesses; central part's and inner-outer macular segments' thickness and volume measurements) segment parameters of groups were similar (p > 0.05). In patient group, as HbA1c level increased, central RNFL and choroidal thicknesses decreased (r = - 0.639, p < 0.001; r = - 0.486, p = 0.010, respectively). CONCLUSIONS: In patients with T1DM, we found that LT increased, and ACD, central RNFL and choroidal thicknesses decreased by OB and OCT before visible findings appeared in routine ophthalmological examination. Determination of early changes is warning to physician and patient in order to prevent more serious damages occurring later.

Childhood-onset mild diabetes caused by a homozygous novel variant in the glucokinase gene.

PURPOSE: Heterozygous loss-of-function mutations in the glucokinase (GCK) gene cause MODY 2, which is characterized by asymptomatic fasting hyperglycemia and does not require insulin treatment. Conversely, homozygous loss-of-function mutations in the same gene give rise to permanent neonatal diabetes mellitus (DM) that appears in the first 6-9 months of life and necessitates lifelong insulin treatment. We aimed to present the genotypic and phenotypic features of a 13-year-old patient diagnosed with DM at the age of 3 years due to a homozygous variant in the GCK gene. METHODS: The patient's clinical and laboratory findings at follow-up were not consistent with the initial diagnosis of type 1 DM; thus, next-generation sequencing of MODY genes (GCK, HNF1A, HNF1B, and HNF4A genes) was performed to identify monogenic causes of DM. RESULTS: A novel homozygous variant c.1222 G > T in the GCK gene was revealed. In silico analysis identified it as a pathogenic variant. His mother, father, and brother had the same heterozygous variant in the GCK gene and were diagnosed with MODY 2 (mild fasting hyperglycemia and elevated HbA1c) after genetic counseling. CONCLUSION: In this case report, a patient with a homozygous variant in the GCK gene, who was diagnosed with DM after the infantile period, was presented, highlighting the fact that cases with homozygous variants in the GCK gene can, though rarely, present at a later age with a milder phenotype.

A rare endocrinological complication of chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) may lead to increase in serum levels of peptide hormones as a result of changes in peripheral metabolism. The pathogenesis of uremic hyperprolactinemia in CKD is not fully understood. Plasma prolactin levels are elevated in women, pubertal girls, and also in men with chronic kidney disease. But this is not comon in prepubertal boys. Also in prepubertal children and postmenopausal women, hyperprolactinemia rarely results in galactorrhea. We aimed to discuss hyperprolactinemia and galactorrhea in a 12-year-old male with CKD. CASE: A twelve-year-old boy with chronic kidney disease (CKD) suffered from bilateral galactorrhea. He was on follow-up at Pediatric Nephrology Department from the age of two due to bilateral dysplastic kidney. On physical examination, his weight was - 0.59 SDS, height was -2.82 SDS, Blood pressure was 115 / 72 (75p), stretched penis length was 6 cm, testicular volume was 3mL / 3mL, pubic hair was Tanner Stage 1, breast examination did not reveal plaque on bilateral breast. He was receiving recombinant erythropoietin, sodium bicarbonate, polystyrene sulfonate, calcium acetate, and calcitriol treatments. Glomerular filtration rate was 23ml/min/1.73 m2 (CKD stage IV). Serum prolactin (PRL) was > 200 µg/L (N, 2.64-13.13). The pituitary adenoma was excluded with pituitary and cranial magnetic resonance imaging (gadolinium). Cabergoline (0.5 mg/ twice weekly) was initiated to decrease PRL levels and reduce galactorrhea. In the second week of treatment, serum PRL level was suppressed (0.4 µg/L) and galactorrhea was completely resolved. CONCLUSIONS: Although uremic hyperprolactinemia is very rarely seen in childhood, it is important to evaluate, and initiate an appropriate treatment since it is associated with delayed puberty and infertility in adulthood in many cases.