Homocysteine metabolism in children and adolescents with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) belongs to a family of rare heterogeneous, genetic disorders characterized by blistering of the skin and mucous membranes in response to minor mechanical trauma. The involvement of the oral mucosa and oesophagus stenosis is suggested to be responsible for severe nutritional deficiencies, but few studies have till now considered this aspect. This observational study aimed to evaluate homocysteine status in children and adolescents with EB by assessing total plasma homocysteine (tHcy) and metabolically related vitamins (B6, B12, folate) concentrations. METHODS: Twenty EB patients (12 M; age range 0.5-19 years) were evaluated for: plasma tHcy, serum B12 and holotranscobalamin (HoloTC, the active fraction of B12), serum and erythrocyte folate (s-F and Ery-F, respectively), plasma B6 and serum high sensitive C-reactive-protein (hsCRP) levels. Clinical severity was also evaluated through the Birmingham Epidermolysis Bullosa Severity (BEBS) score. A sex and age well-matched population was also enrolled. RESULTS: EB patients showed tHcy levels higher (p = 0.04) and B6 levels lower (p = 0.03) than controls. B12, HoloTC, s-F and ery-F concentrations did not differ between patients and controls. Multiple linear regression analysis showed that tHcy levels were independent of the metabolically related vitamins levels. In addition, serum hsCRP levels were higher in EB patients than in controls (p = 0.003) and correlated negatively with B6 concentrations (r = -0.6; p = 0.009). BEBS score correlated negatively with HoloTC (p = 0.022) and B6 (p = 0.005) levels and positively with age (p = 0.031) and hsCRP levels (p < 0.001). CONCLUSIONS: The assessment of tHcy and metabolically related vitamin levels describes an important aspect of EB patients' nutritional status which can result essential for their long term care. Monitoring B6 levels in EB patients could be particularly important in order to prevent several complications associated with B6 deficiency and to avoid a B6 excess which sustains an inflammatory condition.

Vaccination in children with inborn errors of metabolism.

Inborn errors of metabolism (IEMs) are a large group of very heterogeneous diseases, and the impact of the available vaccines on children with IEMs may vary depending on the child's metabolic characteristics. The main aim of this review is to re-analyse the administration of vaccines to such children in the light of the most recent data. As a whole, these indicate that children with stable or slowly progressing IEMs can receive the recommended schedules of all of the recommended vaccinations. However, vaccines should be administered more cautiously to children with IEMs associated with a significant risk of morbidity and/or mortality with catabolic events: i.e. under strict medical supervision, and only when the children are clinically well and their metabolic condition is acceptably controlled. Furthermore, a number of IEMs have been associated with immune deficiency although, in most cases, the immunological abnormalities disappear or are significantly reduced when the metabolic defect is corrected. The response to vaccines is therefore unpredictable, but it is reasonable to think that it may be inadequate in children with the most severe immune defects. In addition to defective protection, vaccines administered to children with IEM and severe immunodeficiency can actually cause the disease they were meant to prevent. This explains why experts suggest that vaccines based on live attenuated viruses should not be given to such children, although all of the other vaccines can be administered without limitation regardless of the type of immune defect. Nevertheless, only specific multicentre studies will make it possible to say when and how to use vaccines in children with different types of IEM in order to protect them from vaccine-preventable diseases without any risk of worsening their metabolic situation.

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

BACKGROUND: In infants, vitamin B12 deficiency may be due to an inborn error of absorption and metabolism, or nutritional problems. CASE PRESENTATION: An 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. CONCLUSION: This 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.

Neonatal atypical hemolytic uremic syndrome due to methylmalonic aciduria and homocystinuria.

BACKGROUND: Inborn errors of cobalamin (Cbl) absorption and metabolism form a large group of rare diseases that include Cbl-C disorder. Among the renal complications of Cbl-C disorder, atypical hemolytic uremic syndrome (HUS) is the least common and has been described only in a small number of cases. CASE-DIAGNOSIS/TREATMENT: Four patients were admitted to our clinic after 15-30 days of life with vomiting associated with poor sucking, failure to thrive, lethargy and hypotonia. Examinations showed thrombocytopenia and microangiopathic hemolytic anemia associated with renal damage. The neonates had high blood homocysteine levels, increased urinary levels of both homocystine and methylmalonic acid, increased propionylcarnitine (C3) levels and an increased C3/acetylcarnitine ratio. Homozygosity for c.271-272dupA (p.Arg91LysfsX14) of the MMACHC gene was detected in three patients, and heterozygosity for c.271-272dupA and c.666C > A(p.Tyr222X) in one patient, which confirmed the diagnosis of Cbl-C disorder. Treatment with parenteral hydroxycobalamin in combination with folic acid and betaine gradually normalized the metabolic test findings and hematological and renal parameters after about 1 week. CONCLUSIONS: Atypical HUS in neonates with Cbl-C disorder may be associated with mild to moderate renal involvement also in early-onset disease, and early adequate therapy can reverse renal damage.

Factors conditioning effectiveness of a reminder/recall system to improve influenza vaccination in asthmatic children.

In order to verify whether a telephone recall system directly managed by pediatricians who usually follow up children for their asthma is more effective than an anonymous recall system, we randomly assigned 285 asthmatic children (177 males; mean age 10.3+/-3.4 years) to one of three groups: those whose mothers were to be called by a pediatrician not previously involved in caring for their asthmatic children and who received the vaccine in our immunisation clinic (group 1); those whose mothers were to be called by a pediatrician from our asthma clinic and who received the vaccine in the immunisation clinic (group 2); and those whose mothers were to be called by a pediatrician from our asthma clinic and who received the vaccine in the same clinic (group 3). Our findings highlight that the use of a reminder/recall system increases vaccination rates in asthmatic children, and show that the best results are obtained when the mothers are contacted and the vaccine administered by the pediatricians who usually follow up the child for asthma.

Attitudes and knowledge regarding influenza vaccination among hospital health workers caring for women and children.

This cross-sectional study of 340 obstetrics/gynecology, 123 neonatology, and 244 pediatric health care workers (HCWs) was designed to evaluate compliance with recommendations concerning the use of influenza vaccine during pregnancy and among pediatric subjects. The results clearly show that only a marginal number of the HCWs in all three fields currently recommend vaccine use for pregnant women and healthy young children. Moreover, all of the HCWs were seriously deficient in terms of their general knowledge of influenza prevention and their own personal vaccination coverage was low. Extensive and sustained efforts to overcome cultural limitations concerning influenza and its prevention are urgently required among HCWs caring for women and children in order to ensure effective compliance with the current recommendations.