An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes.

Young XLH Patients-Reported Experience with a Supportive Care Program.

Purpose: X-linked hypophosphatemia (XLH) is a rare, chronic, genetic condition characterized by renal phosphate wasting and abnormal bone and teeth mineralization. It represents a challenging and multifaceted disease that causes wide-ranging impacts on patients' lives. In this context, a scientific committee has designed a support initiative for patients treated for XLH: the aXess program.

Mouse Models of Mineral Bone Disorders Associated with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) inevitably develop mineral and bone disorders (CKD-MBD), which negatively impact their survival and quality of life. For a better understanding of underlying pathophysiology and identification of novel therapeutic approaches, mouse models are essential. CKD can be induced by surgical reduction of a functional kidney mass, by nephrotoxic compounds and by genetic engineering specifically interfering with kidney development.

Diagnosis and management of mineral and bone disorders in infants with CKD: clinical practice points from the ESPN CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce.

Background: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce.

Methods: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2-5 or on dialysis.

Hydration and Nephrolithiasis in Pediatric Populations: Specificities and Current Recommendations.

Renal lithiasis is less frequent in children than in adults; in pediatrics, lithiasis may be caused by genetic abnormalities, infections, and complex uropathies, but the association of urological and metabolic abnormalities is not uncommon. The aim of this study is to provide a synthesis of nephrolithiasis in children and to emphasize the role of hydration in its treatment. As an etiology is reported in 50% of cases, with a genetic origin in 10 to 20%, it is proposed to systematically perform a complete metabolic assessment after the first stone in a child.

Prospective Analysis of Muscle Adiposity in Children With X-linked Hypophosphatemic Rickets vs Control Children.

Context: Children with X-linked hypophosphatemic (XLH) rickets have muscle weakness that severely impairs their function. Intermuscular and intramuscular adipose tissue (IMAT and intraMAT, respectively) may contribute to this muscle weakness.

Objective: This work aimed to compare IMAT and intraMAT in XLH children vs typically developing (TD) children.

The Tyrosine Phosphatase SHP2: A New Target for Insulin Resistance?

The SH2 containing protein tyrosine phosphatase 2(SHP2) plays essential roles in fundamental signaling pathways, conferring on it versatile physiological functions during development and in homeostasis maintenance, and leading to major pathological outcomes when dysregulated. Many studies have documented that SHP2 modulation disrupted glucose homeostasis, pointing out a relationship between its dysfunction and insulin resistance, and the therapeutic potential of its targeting. While studies from cellular or tissue-specific models concluded on both pros-and-cons effects of SHP2 on insulin resistance, recent data from integrated systems argued for an insulin resistance promoting role for SHP2, and therefore a therapeutic benefit of its inhibition.

Nephrocalcinosis in very low birth weight infants: incidence, associated factors, and natural course.

Background: Preterm kidney is exposed to various exogenous factors that may impact its function such as nephrotoxic drugs or nephrocalcinosis. We investigated prevalence and risk factors of nephrocalcinosis (NC) in recently born very low birth weight (VLBW) infants submitted to improved biological monitoring.

Methods: Retrospective, case-control study in very preterm infants (< 32 + 6 weeks, ≤ 1500 g) admitted to a tertiary care unit during a 6-year period.

Muscle and Bone Impairment in Infantile Nephropathic Cystinosis: New Concepts.

Cystinosis Metabolic Bone Disease (CMBD) has emerged during the last decade as a well-recognized, long-term complication in patients suffering from infantile nephropathic cystinosis (INC), resulting in significant morbidity and impaired quality of life in teenagers and adults with INC. Its underlying pathophysiology is complex and multifactorial, associating complementary, albeit distinct entities, in addition to ordinary mineral and bone disorders observed in other types of chronic kidney disease. Amongst these long-term consequences are renal Fanconi syndrome, hypophosphatemic rickets, malnutrition, hormonal abnormalities, muscular impairment, and intrinsic cellular bone defects in bone cells, due to mutations.

Prenatal features and neonatal management of severe hyperparathyroidism caused by the heterozygous inactivating calcium-sensing receptor variant, Arg185Gln: A case report and review of the literature.

Background: Loss-of-function variants in the calcium-sensing receptor () gene are known to be involved in a clinical spectrum ranging from asymptomatic familial hypocalciuric hypercalcemia (FHH) to neonatal severe hyperparathyroidism (NSHPT). Homozygous or compound heterozygous variants are usually responsible for severe neonatal forms, whereas heterozygous variants cause benign forms. One recurrent pathogenic variant, p.

X-linked hypophosphatemia and burosumab: Practical clinical points from the French experience.

Hereditary hypophosphatemia with increased FGF23 levels are rare inherited metabolic diseases characterized by low serum phosphate because of impaired renal tubular phosphate reabsorption. The most common form is X-linked hypophosphatemia (XLH), secondary to a mutation in the PHEX gene. In children, XLH is often manifested by rickets, delayed development of gait, lower limb deformities, growth retardation, craniosynostosis, and spontaneous dental abscesses.

Cinacalcet use in paediatric dialysis: a position statement from the European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders Working Group of the ERA-EDTA.

Secondary hyperparathyroidism (SHPT) is an important complication of advanced chronic kidney disease (CKD) in children, which is often difficult to treat with conventional therapy. The calcimimetic cinacalcet is an allosteric modulator of the calcium-sensing receptor. It has proven to be effective and safe in adults to suppress parathyroid hormone (PTH), but data on its use in children are limited.

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes.