Agnieszka Szmigielska

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy characterized by obesity, retinal dystrophy, cognitive impairment, hypogonadism, and congenital renal anomalies, which represent a leading cause of morbidity and mortality in affected patients. We followed four patients with BBS (three boys, one girl) from birth to ten years of age. In all children, we assessed physical development, laboratory tests, including assessment of renal function, renal ultrasound examination, and blood pressure control. Patients (three males) with Bardet-Biedl syndrome, demonstrated prenatal and postnatal evidence of structural and functional renal abnormalities, including kidney injury and bilateral renal dysplasia. Neonatal serum creatinine ranged from 0.70 to 1.66 mg/dL, with persistently abnormal renal morphology on follow-up imaging and variable but overall stable renal function (latest creatinine 0.68–1.03 mg/dL). Arterial hypertension occurred in one male and one female patient and was effectively controlled with angiotensin-converting enzyme inhibitor therapy. All patients exhibited multisystem involvement characteristic of ciliopathy, including polydactyly, obesity, ophthalmologic abnormalities, neurodevelopmental impairment, and hypogonadism in three of four individuals. The broad spectrum of renal manifestations in BBS underscoring the importance of early diagnosis and individualized nephrological monitoring.

Background: In polycystic kidney diseases, increased periostin levels and disease progression are observed. Multicystic dysplastic kidney (MCDK) is characterized by kidney atrophy. The aim of the study is to assess serum periostin activity in children with MCDK and in patients with MCDK and involution of cysts. Methods: We enrolled in the study 64 children aged 1–5 years (mean age 25 +/− 9 months). Serum periostin (sPOSTN) levels were measured using enzyme-linked immunosorbent assay. We divided children into three groups: group A—patients with MCDK and cysts (n = 34); group B—patients with involution of cysts or after nephrectomy (n = 10), and group C—healthy children (n = 20). Results: Blood samples were obtained from 64 children, including 44 children with MCDK (26 boys, 18 girls). sPOSTN levels were significantly higher in group A, 239.1 ± 168.1 [IQR: 62.4, 385.7] ng/mL, compared to group B, 77.7 ± 82.8 [IQR: 31.7, 117.0] ng/mL (p < 0.05). The median level of periostin in patients with MCDK (groups A and B) was 204.4 ± 168.2 [IQR: 34.9, 363.4] ng/mL and 141.1 ± 129.0 [IQR: 30.3, 276.9] ng/mL in group C, respectively. In patients with the renal cysts, the cut-off value of periostin was 133.57 ng/mL. The lowest level of periostin was observed in patients in group B. There were no significant differences in periostin level between groups B and C. Conclusions: The study shows that a high level of sPOSTN was identified in patients with MCDK and cyst presentation in abdominal ultrasonography. The level of sPOSTN could be a promising blood marker of the cyst’s formation in cystic kidney diseases. However, this study remains preliminary; further studies are needed to confirm our findings.

Background: Diabetes insipidus (DI) in newborns is an extremely rare condition, with the age of presentation strongly suggesting a genetic background of the disease. The differential diagnosis should include arginine vasopressin deficiency (AVD) and arginine vasopressin resistance (AVR). Some novel diagnostic tools such as copeptin evaluation and genetic tests are vital for early diagnosis. Case report: We present the case of a 1-month-old boy with polyuria observed since birth. Laboratory tests showed persistent hypernatremia, elevated plasma and low urine osmolality. An attempt at oral administration of desmopressin had no effect; additionally the copeptin level was increased. A genetic study (NGS of the AVP, AVPR2 and AQP2 genes) was considered and a new pathogenic variant in the AVPR2 gene (hemizygous c.157del) was detected. After the genetic test result was obtained, treatment with hydrochlorothiazide was started. The patient is now 3 months old, developing normally, and the weight and height are normal. Conclusions: Newborns with DI should be subjected to extensive multidisciplinary diagnostics, including endocrine and renal causes. Copeptin evaluation and prompt genetic diagnosis allows for the early diagnosis and implementation of appropriate treatment.

A Transient Ischemic Attack (TIA) in children results from a temporary interruption of blood flow to the brain, leading to brief neurological symptoms. The most common causes of pediatric TIA include congenital heart defects and vascular anomalies. We present a 10-year-old girl with neurological symptoms due to subclavian steal syndrome. Physical examination revealed an asymmetry in blood pressure measurements between the upper limbs, exceeding 30 mmHg. Echocardiography revealed a right-sided aortic arch (RAA) with an atypical configuration of the cephalic vessels. Ultrasound of the vertebral arteries demonstrated reversed flow direction in the left vertebral artery. CT angiography confirmed RAA and an atypical branching pattern. The left subclavian artery was narrower with critical stenosis in its proximal segment, adjacent to the origin of the ductus arteriosus. The girl was qualified to surgical intervention to correct the incomplete vascular ring associated with a RAA and an aberrant left subclavian artery.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are developmental disorders that commonly cause pediatric chronic kidney disease and mortality. We examine here rare coding variants in 248 CAKUT trios and 1742 singleton CAKUT cases and compare them to 22,258 controls. Diagnostic and candidate diagnostic variants are detected in 14.1% of cases. We find a significant enrichment of rare damaging variants in constrained genes expressed during kidney development and in genes associated with other developmental disorders, suggesting phenotype expansion. Consistent with these data, 18% of CAKUT patients with diagnostic variants have neurodevelopmental or cardiac phenotypes. We identify 40 candidate genes, including CELSR1, SSBP2, XPO1, NR6A1, and ARID3A. Two are confirmed as CAKUT genes: ARID3A and NR6A1. This study suggests that many yet-unidentified syndromes would be discoverable with larger cohorts and cross-phenotype analysis, leading to clarification of the genetic and phenotypic spectrum of developmental disorders.

Diabetes insipidus (DI) in newborn is an extremely rare condition, simultaneously the age of presentation is a strong suggestion of genetic background of disease. The differ-ential diagnosis should include arginine vasopressin deficiency (AVD) and arginine vasopressin resistance (AVR). Some novel diagnostic tools such as copeptin evaluation and genetic tests are vital for the early diagnosis. Case report: We present the case of a 1-month-old boy with polyuria observed since birth. Laboratory tests showed persis-tent hypernatremia, elevated plasma and low urine osmolality. An attempt at oral administration of desmopressin had no effect, additionally copeptin level was in-creased. A genetic study (NGS of the AVP, AVPR2 and AQP2 genes) was taken and a new pathogenic variant in the AVPR2 gene (hemizygous c.157del) was detected. After the genetic test result was obtained, treatment with hydrochlorothiazide was started. The patient is now 3 months old, developing normally, weight and height are normal. Conclusions: A newborn with DI should be subjected to extensive multidisciplinary diagnostics including endocrine and renal causes. Copeptin evaluation and prompt genetic diagnosis allows for early diagnosis and implementation of appropriate treat-ment.

The triad of symptoms: renal defects, congenital inferior vena cava agenesis (IVCA) and deep vein thrombosis of the lower limbs make up the KILT syndrome (kidney and IVC abnormalities with leg thrombosis). A 17-year-old boy complained of periodic abdominal pain. Abdominal ultrasonography revealed a multilocular cyst in the right kidney. Physical examination showed no abnormalities, and his blood pressure was 120/80mmHg. Abdominal ultrasonography showed a cyst measuring 36×30×25mm in the right kidney hilum. Computed tomography did not show the hepatic and suprarenal sections of the inferior vena cava. Numerous varicose-dilated collateral vessels, including renal venous vessels, were found in the right kidney hilum. The collateral vessels in the tomography matched the described in the ultrasound renal cyst. MRI confirmed IVCA with no other additional vascular abnormalities. Due to the risk of deep vein thrombosis of the lower limbs, non-pharmacological antithrombotic prophylaxis was recommended. Early detection of inferior vena cava agenesis allows for the reduction of the risk of dangerous thrombotic complications.

Rare disease Pseudohypoaldosteronism (PHA) is characterized by renal tubular resistance to aldosterone and leads to hyponatremia, hyperkalemia, and metabolic acidosis. PHA is divided into 2 types: PHAI and PHAII. PHAI can be dominant (systemic disease) or recessive (renal form). PHAII causes hypertension with hyperkalemia and is recognized mostly in adults. PHA can be a life-threatening disease due to salt-wasting syndrome and severe hypovolemia. We describe the case of a 2-month-old girl who was admitted to our hospital with hypovolemic shock due to salt-wasting syndrome. Laboratory tests revealed severe electrolyte abnormalities: hyponatremia (Na-116 mmol/L), hyperkalemia (K-10 mmol/L) and metabolic acidosis (pH-7.27; HCO3-12 mmol/L). Serum aldosterone was >100 ng/dL. Genetic analysis confirmed mutations in SCNN1A and CUL3 gene responsible for PHAI and PHAII. Supplementation with NaCl, pharmacological treatment of hyperkalemia, and restriction of potassium in the diet resulted in the normalization of serum electrolytes and proper future development. Pseudohypoaldosteronism should always be considered in the differential diagnosis of hyponatremia and hyperkalemia in children. Salt loss syndrome can lead to hypovolemic shock and, when unrecognized and untreated, to death of a child due to arrythmias and brain edema. The presence of 2 types of PHA in the same patient increases the risk of salt loss and at the same time significantly increases the risk of hypertension because of genetic predisposition and regular diet. Increased salt concentration in sweat and saliva may suggest pseudohypoaldosteronism.

Anemia of inflammation (IA), the second most common cause of childhood anemia, results from macrophage iron sequestration and impaired erythropoiesis. Neutrophil gelatinase-associated lipocalin (NGAL) plays an important role in innate microbial immunity through its influence on intracellular iron homeostasis and inhibition of erythropoiesis. The predictive value of NGAL in IA was assessed in 74 children (age 6.30 ±3.64 months) with the first episode of urinary tract infection (UTI). Anemia of inflammation was found in 50% of children, including those with non-febrile UTI, and delayed onset of anemia was observed in 20% of children. There were no differences in NGAL levels between the anemic and non-anemic children, and no correlations between NGAL and hemoglobin (HGB) levels and red blood cell (RBC) count. In multivariate logistic regression analysis elevated C-reactive protein (CRP) was only independently associated with the presence of anemia in children with UTI [OR (95% CI): 1.128 (1.005-1.265), p = 0.040]. In stepwise multiple analysis age independently correlated with RBC ( = 0.051, p = 0.001), while CRP independently correlated with HGB ( = –0.037, p = 0.027) and RBC ( = –0.022, p = 0.014). ROC analysis demonstrated better diagnostic profiles for CRP, procalcitonin (PCT) and fever duration for predicting the risk of IA than NGAL (AUC: 0.690, 0.669, 0.678 vs. 0.638, respectively). Despite the increase in HGB levels after 4-5 weeks from the onset of UTI, HGB values were still significantly lower in the anemic than in non-anemic children. NGAL was not useful for predicting IA in UTI, since its diagnostic value was inferior to conventional inflammatory markers.