Glomerulonephritis and nephrotic syndrome in a child with DiGeorge syndrome: Questions

An infant with hyponatremia, hyperkalemia, and metabolic acidosis associated with urinary tract infection: Questions

Mild hypotonia and recurrent seizures in an 8-month-old boy: Answers

Glomerulonephritis and nephrotic syndrome in a child with DiGeorge syndrome: Answers

Mild hypotonia and recurrent seizures in an 8-month-old boy: Questions Abstract Hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder which manifests in early infancy with generalized seizures, other symptoms of neuromuscular irritability, and growth disturbances. Homozygous mutations in the magnesium transporter gene, transient receptor potential melastatin 6 (TRPM6), cause the disease. Here, we present an 8-month-old Turkish boy with a novel mutation of TRPM6. The patient, son of first-degree cousins, was hospitalized because of recurrent seizures and mild hypotonia. He had seizures since the newborn period and he had been treated with phenobarbital but there was no favorable response to therapy. His past history also revealed hypocalcemia detected on the newborn period but serum magnesium levels were not studied at that time. During hospitalization, we detected hypocalcemia, hypomagnesemia, and normal parathormone levels. Abdominal ultrasound was normal. Magnesium excretion was slightly increased. Considering the consanguinity of the parents and clinical features of the patients, genetic testing of the TRPM6 gene was performed and a novel homozygous mutation was detected as c.3178A>T. He was started on magnesium and calcium supplementation and he is symptom-free for 1 year. We would like to call attention to the measurement of serum magnesium levels in children with hypocalcemic convulsions. Early and appropriate treatment with magnesium supplementation is crucial.

Defining urinary tract infection by bacterial colony counts: a case for less than 100,000 colonies/mL as the threshold

An infant with hyponatremia, hyperkalemia, and metabolic acidosis associated with urinary tract infection: Answers

Defining urinary tract infection by bacterial colony counts: a case for 100,000 colonies/ml as the best threshold

Kidney as modulator and target of “good/bad” HDL Abstract The strong inverse relationship between low levels of high-density lipoproteins (HDLs) and atherosclerotic cardiovascular disease (CVD) led to the designation of HDL as the “good” cholesterol. The atheroprotection is thought to reflect HDL’s capacity to efflux cholesterol from macrophages, followed by interaction with other lipoproteins in the plasma, processing by the liver and excretion into bile. However, pharmacologic increases in HDL-C levels have not led to expected clinical benefits, giving rise to the concept of dysfunctional HDL, in which increases in serum HDL-C are not beneficial due to lost or altered HDL functions and transition to “bad” HDL. It is now understood that the cholesterol in HDL, measured by HDL-C, is neither a marker nor the mediator of HDL function, including cholesterol efflux capacity. It is also understood that besides cholesterol efflux, HDL functionality encompasses many other potentially beneficial functions, including antioxidant, anti-inflammatory, antithrombotic, anti-apoptotic, and vascular protective effects that may be critical protective pathways for various cells, including those in the kidney parenchyma. This review highlights advances in our understanding of the role kidneys play in HDL metabolism, including the effects on levels, composition, and functionality of HDL particles, particularly the main HDL protein, apolipoprotein AI (apoAI). We suggest that normal apoAI/HDL in the glomerular filtrate provides beneficial effects, including lymphangiogenesis, that promote resorption of renal interstitial fluid and biological particles. In contrast, dysfunctional apoAI/HDL activates detrimental pathways in tubular epithelial cells and lymphatics that lead to interstitial accumulation of fluid and harmful particles that promote progressive kidney damage.

Nine novel HOGA1 gene mutations identified in primary hyperoxaluria type 3 and distinct clinical and biochemical characteristics in Chinese children Abstract Background Primary hyperoxaluria type 3 (PH3) is characterized by mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 patients are thought to present with a less severe phenotype than PH1 and PH2 patients. However, the clinical characteristics of PH3 patients have yet to be defined in sufficient detail. The aims of this study were to report HOGA1 mutations of PH3 in Chinese children, and to analyze the genotype and clinical characteristics of these PH3 patients. Methods Genetic analysis (targeted gene panel-based and/or whole-exome sequencing) of HOGA1 was performed in 52 patients with a high suspicion of PH3, and DNA was obtained from the patient and both the parents. The clinical, biochemical, and genetic data of these 12 patients identified with HOGA1 mutations were subsequently retrospectively reviewed. Results These 12 patients were identified with HOGA1 mutation. The median onset of clinical symptoms was 18.25 (range 5–38) months. In total, 14 different mutations were identified including 9 novel mutations in these 12 patients with PH3. All of these 12 patients initially presented with urolithiasis, and 3 patients among them comorbid urinary tract infection (UTI) as another initial symptom. Ten patients experienced hyperoxaluria (average oxalate 0.77 mmol/1.73 m2/24h). In contrast, urine calcium excretion was normal in 8 patients and 2 patients with hypercalciuria (urine calcium > 4 mg/kg/24 h). At the time of diagnosis, estimated GFR was 155.6 ml/min per 1.73 m2, and at last follow-up time (17.3 months later from diagnosis on average), estimated GFR was 157.5 ml/min per 1.73 m2. To date, none of the patients has impaired renal function based on and progressed to ESRD. Conclusions We found that PH3 was significantly diagnosed in our urolithiasis patients during childhood. Nine novel HOGA1 mutations were identified in association with PH3, which provide a first-line investigation in Chinese PH3 patients. The eGFR was normal in all children with PH3. This finding is in contrast to the early impairment of renal function in PH1 and PH2.