Sophie Guez

Acute pyelonephritis as a cause of hyponatremia/hyperkalemia in young infants with urinary tract malformations

Obstructive uropathy causes tubular resistance to aldosterone and severe metabolic imbalance may be precipitated by an episode of pyelonephritis. In the last 3 years we investigated 52 episodes of pyelonephritis (positive urine culture, elevated C reactive protein, fever, elevated neutrophil count) in 50 children between 15 days and 15 months of age. Ultrasonography voiding cystography and renal scintiscan were performed in all cases and iv urography in some. A salt‐losing syndrome with hyponatremia and hyperkalemia (Na <125 meq/liter; K >6.3 meq/liter) was observed in 17 infants <3 months, accompanied by plasma aldosterone concentration of 5000 to 23 000 pg/ml (normal value, <1000 pg/ml). All these children had a severe urinary tract (UT) malformation (ureteropelvic junction stenosis in 7 cases, vesicoureteral reflux in 7, posterior urethral valves in 2, double system in 1). Thirteen infants <3 months, 7 with no urinary tract malformations, did not have electrolyte imbalance. Pyelonephritis was diagnosed in 20 other patients ages 4 to 15 months, including 16 with severe UT malformations; 4 had normal UTs. We conclude that a salt-losing syndrome with tubular resistance to aldosterone can occur during pyelonephritis in young infants with congenital UT malformation, that the risk diminishes considerably or disappears after 3 months of age and that in the absence of UT malformation pyelonephritis does not cause acute sodium loss of clinical relevance.

Adequate clinical control of congenital nephrotic syndrome by enalapril.

Abstract. The combination of captopril and indomethacin has been shown to control nephrotic proteinuria in an infant with congenital nephrotic syndrome of the Finnish type. We report the satisfactory control of congenital nephrotic syndrome by enalapril, maintaining normal serum albumin levels without albumin infusions. The haplotype data of our patient were consistent with the diagnosis of a Finnish-type nephrotic syndrome. After 21 months, during which daily infusions of albumin allowed partial control of the symptoms, captopril treatment was started. No adverse effects were noted. Serum creatinine levels remained normal. Within 8 weeks, albumin infusions were completely stopped. After 1 month the treatment was changed to a single dose of enalapril (0.8 mg/kg per day). During the next 15 months, the serum protein concentration was maintained around 6.5–7 g/dl, although proteinuria persisted (0.3–0.5 g/day). Weight and length gain are now satisfactory. We conclude that enalapril may be safely used in infants with severe forms of congenital nephrotic syndrome and might allow the avoidance of aggressive treatments for prolonged periods.

Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old Italian infant born to a mother receiving multivitamin supplementation during pregnancy

BackgroundIn infants, vitamin B12 deficiency may be due to an inborn error of absorption and metabolism, or nutritional problems.Case presentationAn exclusively breastfed 5-month-old Italian male infant, who was born after a normal full-term pregnancy to a vegan mother who was apparently daily treated with a multivitamin oral preparation during the second and third trimester, was hospitalised because of poor weight gain, feeding difficulties, severe pallor, muscle hypotonia and somnolence. Upon admission, his weight, length and head circumference were below the third percentile, he had an enlarged liver and spleen, and showed a significant delay in developmental milestones and communicative reactions. He had a hemoglobin level of 4.7 g/dL with an MCV of 84.2 fL, a white blood cell count of 4,680/mm3, and a platelet count of 45,000/mm3. His serum vitamin B12 level was 57 pg/mL (normal value 180–500 pg/mL) and serum folate level 12.8 ng/mL (normal value >3 ng/mL). The results of metabolic examinations excluded a cobalamin C disorder, whereas nutritional screening showed a serum iron concentration of 9 μg/dL and serum ferritin of 4 ng/mL. Magnetic resonance imaging of the brain showed mild dilatation of the lateral ventricles with diffuse delayed myelination. The child was diagnosed as having vitamin B12 and iron deficiency due to nutritional inadequacy and was immediately treated with packed red blood cells, intramuscular vitamin B12 injections, and iron supplementation. A few days after the start of therapy, his hemoglobin levels and other hematological parameters rapidly improved, and a clinical improvement was observed within few weeks. There was an increase in his achievement of developmental milestones, but his development was still retarded seven months after the start of therapy.ConclusionThis case underlines the importance of adequately controlling maternal vitamin B12 intake during pregnancy by means of supplementation which, in the case of vegan mothers, should be significantly greater than that usually given. Moreover, the supplementation should be continued during lactation in order to avoid the development of signs of deficiency that may be associated with persistent neurological problems in infants. The case also highlights the need to consider vitamin B12 deficiency in infants with severe anemia even if their hematological parameters do not indicate megaloblastic anemia because the concomitant presence of substantial iron deficiency may modify the characteristics of the anemia.

Healthcare transition in patients with rare genetic disorders with and without developmental disability: neurofibromatosis 1 and Williams-Beuren syndrome.

There are between 5,000 and 8,000 distinct rare diseases (RDs) affecting 6–8% of the population, most of which are caused by genetic defects. Many are highly complex, childhood‐onset, multi‐system disorders that are often associated with developmental disability, and require lifelong, highly specialized care and support. As larger numbers of children with previously fatal RDs survive into adulthood, they encounter significant challenges in transitioning from family‐centered, developmentally focused, multidisciplinary pediatric care to a less supportive adult healthcare system that is often unfamiliar with these conditions. This paper discusses the challenges of the transition from pediatric to adult health care in two groups of patients with multisystem genetic RDs (neurofibromatosis 1 [NF1] and Williams–Beuren syndrome [WBS]), and analyzes strategies for making the process easier for patients with and without developmental disabilities. Our findings show that there are still no guidelines in national healthcare programs on how to transition RD adolescents with and without developmental disabilities, and only a few pediatric centers have implemented the elements of transition in their general practice. Evidence regarding programs to facilitate transition is inconclusive and the transition from pediatric medicine to adult medicine for RDs remains a major challenge. However, transition requires both time and personnel, which are difficult to find in periods of fiscal austerity. Nevertheless, we should strongly advocate for governments investing more into transition infrastructure or they will face increased long‐term social and economic costs due to poor treatment compliance, disengagement from services, increased genetic risks, and higher rates of disease‐related complications.

Preliminary evaluation of cord blood platelet gel for the treatment of skin lesions in children with dystrophic epidermolysis bullosa

The common clinical manifestations of EB are mechanical fragility of the skin, blister formation, and abnormal wound healing, but the severity of the skin lesions varies depending on the distinct type of the disease. Junctional EB and dystrophic EB (DEB), the most severe types of EB diseases, usually cause chronic pain and discomfort that can significantly reduce the quality of life of affected

Epidermolysis bullosa and the partnership with autoimmunity: what should we assimilate?

Bullous skin diseases are characterized by genetic abnormalities related to structural epidermal proteins or organ-specific autoantibodies against the same proteins and are revealed by blister formation on skin or mucous membranes, with differences in blister depth, morphology, and topography. Both inherited and autoimmune forms of these disorders can be framed in the context of epidermolysis bullosa. Their clinical spectrum varies from early lethal to mild variants with normal life expectancy, and several distinct phenotypes differ for age of onset, extent, location and depth of skin and mucous lesions, or scarring severity. Recently, different inflammatory processes blended with autoimmune phenomena have been demonstrated in both inherited and acquired epidermolysis bullosa, revealing that this overlapping might cause substantial implications in terms of disease course and outcome. Although several associations between epidermolysis bullosa in its different variants and autoimmune diseases have been reported, it is not yet completely clear how it happens and why this association occurs in only some patients. Autoantibodies are the primary cause of the disease in acquired epidermolysis bullosa, whereas they can be produced as a secondary event due to genetically determined skin damage in inherited epidermolysis bullosa, contributing significantly to the worsening of the disease. The awareness of this overlap may help in identifying new therapeutic approaches with immunosuppressive drugs that could have a significant impact in terms of prognosis.

Nutritional Challenges in Duchenne Muscular Dystrophy

Neuromuscular diseases (NMDs) represent a heterogeneous group of acquired or inherited conditions. Nutritional complications are frequent in NMDs, but they are sometimes underestimated. With the prolongation of survival in patients with NMDs, there are several nutritional aspects that are important to consider, including the deleterious effects of overnutrition on glucose metabolism, mobility, and respiratory and cardiologic functions; the impact of hyponutrition on muscle and ventilatory function; constipation and other gastrointestinal complications; chewing/swallowing difficulties with an increased risk of aspiration that predisposes to infectious diseases and respiratory complications; as well as osteoporosis with an associated increased risk of fractures. The aim of this review is to provide a comprehensive analysis of the nutritional aspects and complications that can start in children with Duchenne muscular dystrophy (DMD) and increase with ageing. These aspects should be considered in the transition from paediatric clinics to adult services. It is shown that appropriate nutritional care can help to improve the quality of life of DMD patients, and a multidisciplinary team is needed to support nutrition challenges in DMD patients. However, studies on the prevalence of overnutrition and undernutrition, gastrointestinal complications, infectious diseases, dysphagia, and reduced bone mass in the different types of NMDs are needed, and appropriate percentiles of weight, height, body mass index, and body composition appear to be extremely important to improve the management of patients with NMD.

Autoimmunity and cytokine imbalance in inherited epidermolysis bullosa

In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB) types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1) desmoglein 3 (DSG3), bullous pemphigoid 180 (BP180), BP230 and type VII collagen (COL7), respectively). The same trend was observed for interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-β, and interferon-γ (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively). Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS) scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively) and IL-6 (p = 0.03), whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively). This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease.

Ehlers-Danlos syndrome versus cleidocranial dysplasia

Dear Sir, The early identification of hereditary syndromes is essential for planning medical and surgical interventions for reducing the risk of complications [1]. Unfortunately, clinical phenotypes of hereditary syndromes in the first years of life and in mild cases are often poorly characterized. Some disease symptoms are also common to several different genetic conditions. Cleidocranial dysplasia (CCD, OMIM #119600) is a genetic condition that predominantly affects the skeletal system. Typical CCD features include persistently open skull sutures, clavicular hypoplasia/aplasia, and dental anomalies [2,3]. CCD is caused by a heterozygous loss-of-function mutation in the RUNX2 gene [2,3]. However, the abnormal shoulder and arm mobility commonly observed in CCD is also typical of other syndromes, particularly hypermobile Ehlers-Danlos syndrome (EDS-HT). EDS-HT is marked by joint laxity with minimal skin changes and no skin fragility [4] but does not have additional specific clinical features and cannot be diagnosed through laboratory tests. The child characterized in this report was initially misdiagnosed with EDS-HT when the correct diagnosis was CCD. CCD was confirmed by genetic findings but not until several years later. The male proband was the second child born to healthy, non-consanguineous Caucasian parents. The family history was unremarkable and did not indicate a history of mental retardation, genetic diseases, or birth defects. The child was born at 35 weeks of gestational age as the result of a premature membrane rupture after an uneventful pregnancy. At birth, he weighed 2,700 gr and had a body length of 45.5 cm, occipital frontal diameter of 30 cm, and an APGAR score of 9/10. The patient’s medical history after reaching school age was unremarkable, and he had normal body and psychomotor growth. However, delayed anterior fontanel closure and prolonged deciduous dentition retention were reported. At nine years of age, the patient experienced constant bilateral shoulder dislocation associated with bilateral flat foot and the delayed eruption of permanent teeth. The patient was evaluated by a pediatrician with experience in the clinical genetics field and was diagnosed with EDS-HT. At 13 years of age, the patient entered the pediatric

Unusual prenatal presentation of rubinstein-taybi syndrome: A case report

Rubinstein–Taybi syndrome (RTS) is a rare multiple congenital anomalies‐intellectual disability syndrome. The diagnosis is made after birth and based on the detection of signs such as growth and developmental delay, minor facial anomalies, and broad thumbs and halluces. It is rare to suspect RTS during the prenatal period. We report here the approach to a patient with RTS whose pregnancy was complicated by multiple congenital anomalies. However, in the presence of the broad thumb and facial anomalies, we were able to suggest the correct diagnosis. The RTS was confirmed at birth and the molecular analysis of the major causative gene revealed a previously unreported heterozygous truncating mutation of CREBBP. This report provides new knowledge of the fetal phenotype of RTS.