Different Phenotypes of Schimke Immuno-Osseous Dysplasia (SIOD) in Two Sisters with the Same Mutation in the SMARCAL1 Gene.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a very rare autosomal recessive genetic disease caused by mutations in the SMARCAL1 gene. It is characterized by spondyloepiphyseal dysplasia, T-cell immunodeficiency, hypercromic nevi, hypercholestero-lemia, and steroid-resistant nephrotic syndrome with progressive renal failure to end-stage kidney disease. CASE PRESENTATION: We report two cases of SIOD in sisters, diagnosed after the debut of nephrotic syndrome. Both had a personal history of short stature, acetabular hip dysplasia, and hypercholesterolemia. The first case, a 6-year-old girl, presented peripheral refractory edema, severe arterial hypertension, and progressive decrease of the glomerular filtration rate. Steroid-resistance of nephrotic syndrome was confirmed, treated with tacrolimus without response. Renal function worsened over the following 4 months, so haemodialysis was started. Her sister, a 5-year-old girl, had the steroid-resistant nephrotic syndrome and normal blood pressure and renal function under enalapril treatment. In view of the suspicion of SIOD, genetic studies were carried out, revealing the same mutation in homozygosis. CONCLUSION: SIOD has a variable expression with multi-systemic involvement with a short life expectancy. Early diagnosis is important, which can encourage the early start of treatment and anticipation of complications that may be life-threatening.

Left Ventricular Hypertrophy in Patients with X-Linked Hypophosphataemia

X-linked hypophosphatemia (XLH) is a rare genetic disorder with X-linked dominant inheritance. Mutations in the PHEX gene increase fibroblast growth factor 23 (FGF23) concentrations, causing loss of phosphorus at the proximal tubule. Most pediatric patients debut in the first two years with short stature and bowed legs. Conventional treatment consists of oral supplements with phosphorus and calcitriol. Since 2018, burosumab has been approved as a novel therapeutic option for XLH, with promising results. The purpose of this study was to share our experience with two cases of XLH treated with burosumab. These patients presented with a broad phenotypical differences. One had the most severe radiological phenotype and developed left ventricular hypertrophy (LVH) and left ventricular dysfunction with preserved ejection fraction. Treatment with burosumab was well-tolerated and was followed by radiological stability and a striking improvement in both blood biochemistry and quality of life. The LVH was stable and left ventricular function normalized in the patient with cardiac involvement. In recent years many studies have been carried out to explain the role of FGF23 in cardiovascular damage, but the exact pathophysiological mechanisms are as yet unclear. The most intensively studied populations are patients with XLH or chronic kidney disease, as both are associated with high levels of FGF23. To date, cardiovascular involvement in XLH has been described in patients treated with conventional treatment, so it would be of interest to investigate if early use of burosumab at the time of diagnosis of XLH would prevent the occurrence of cardiovascular manifestations.

Lung ultrasound score and diuretics in preterm infants born before 32 weeks: A pilot study.

OBJECTIVE: To describe if weekly determined lung ultrasound (LU) scores in preterm infants born before 32 weeks (PTB32W) change with diuretic therapy. DESIGN: We included infants who received diuretics and compared LU scores according to their evolution on respiratory support (RS) before and after diuretics. RESULTS: We included 18 PTB32W divided into two groups. Both groups were similar in terms of median gestational age: 26 weeks (interquartile range [IQR]: 25-28) in the responders' group and 27 weeks (IQR: 24-28) in the other. They differed, however, in the median number of days on invasive mechanical ventilation: 27 (IQR: 11-43) versus 76 (IQR: 35-117), p = .03; in addition to the number of infants with moderate-severe bronchopulmonary dysplasia: 3 (33%) versus 8 (89%), p = .025. The responders' group showed lower LU scores 2 days after diuretics, with a median LU score of 6 (IQR: 3-12) versus 14 (IQR: 12-17) in the nonresponders group, p = .03; 1 week after (3 [IQR: 0-10] versus 12 [12-12], p = .04); and 3 weeks after (5 [IQR: 3-6] versus 12 [10-15], p = .01). RS also decreased at the same time: 7 out of 9 (78%) were extubated in the responders' group, and 1 out of 9 (11%) in the nonresponders group, p = .02, and these differences remained throughout the entire follow-up. CONCLUSIONS: There is a group of PTB32W patients whose LU score improves after diuretics. This change appears only in those patients that can be weaned off from RS, and at the same period of time as the administration of diuretics.