Tubulointerstitial damage is a common diabetic kidney disease (DKD) complication caused by diabetes mellitus. However, many patients may not present with albuminuria or impaired glomerular filtration rate (GFR), making it difficult to detect kidney dysfunction. Kidney injury molecule-1 (KIM-1) is an emerging biomarker of early DKD, reflecting tubular injury before glomerular dysfunction. We explored the association between KIM-1 and DKD in children and adolescents with type 1 diabetes (T1D). We included 10 studies with 842 participants published between 2016 and 2025. A literature search of MEDLINE/PubMed, Cochrane Library, and Scopus was conducted from inception through January 5, 2026. The mean difference with a 95% confidence interval (CI) was calculated, and a P-value of <0.05 was considered statistically significant. A quality assessment of the included studies was conducted using the Newcastle-Ottawa Scale. In the meta-analysis of four studies, the urinary KIM-1 (uKIM-1)/creatinine ratio was elevated before changes in estimated GFR (95% CI, 0.02–0.48; P=0.03). This review suggests that uKIM-1/creatinine ratio and uKIM-1 may act as promising tubular biomarkers associated with early kidney injury in pediatric patients with T1D. However, further data are needed to clarify their role in pediatric DKD.

Pseudohypoparathyroidism type 1A (PHP1A) is a rare disease caused by molecular defects in the maternally-inherited allele of the guanine nucleotide-binding protein, α-stimulating (GNAS) gene. The GNAS gene encodes the stimulatory G-protein α-subunit that regulates production of the second messenger cyclic adenosine monophosphate. Heterozygous inactivating mutations in these specific loci are responsible for a spectrum of phenotypic characteristics of the disease, including clinical features of the Albright’s hereditary osteodystrophy, due to resistance to parathyroid hormone (PTH). We report a case of PHP1A and explore the underlying novel point mutation of the GNAS gene that leads to an atypical PHP1A phenotype. A male patient with a round face, short stature, and brachydactyly accompanied by normocalcaemia and mild PTH resistance consulted at our center. The GNAS encoding region from the patient and both of his parents were amplified and sequenced directly in a sample of peripheral blood leukocytes. A novel c.389A>G point mutation in exon 5 of the GNAS gene, resulting in a p.Tyr130Cys peptidic chain change of the Gsα protein, detected in the proband, in heterozygous state. Sequencing of the GNAS gene from his parents did not reveal the c.389A>G mutation, confirming a de novo proband genotype. The maternal origin of the affected GNAS allele, along with mild PTH resistance, confirmed the PHP1A diagnosis. PHP1A, caused by inactivating GNAS mutations, presents a range of complex clinical phenotypes. The novel c.389A>G GNAS mutation presented in this case expands the spectrum of known PHP1A molecular defects and describes the associated phenotype.

X-linked adrenal hypoplasia congenita (AHC) is a rare disorder that usually presents clinically as adrenal insufficiency in early infancy. It is caused by mutations in the NR0B1 gene which is located on the short arm of chromosome X (Xp21). The NR0B1 gene plays an important role in normal development and function of both the adrenal and gonadal axes and some patients with the disease can present in adolescence with hypogonadotropic hypogonadism. Testicular microlithiasis is an ultrasonographic finding of unknown etiology that has been associated with several benign conditions such as cryptorchidism, congenital adrenal hyperplasia, varicoceles, and testicular malignancy. We report the case of an 11-year-old boy who was diagnosed at the age of 8 months with X-linked AHC due to adrenal failure and presented testicular microlithiasis during follow-up. To the best of our knowledge, this is the first case of an X-linked AHC patient diagnosed with testicular microlithiasis in follow-up.
Adolescent ; Adrenal Hyperplasia, Congenital ; Adrenal Insufficiency ; Arm ; Child ; Cryptorchidism ; Follow-Up Studies ; Gonads ; Humans ; Hypogonadism ; Male* ; Varicocele