Asfotase Alfa Treatment in a 2-year-old Girl with Childhood Hypophosphatasia

Childhood hypophosphatasia (HPP) presents with bowing of the limbs, poor mobility, chronic pain, short stature, fractures, and motor impairment. Enzyme replacement therapy (ERT) provides improved pulmonary and physical function in life-threatening perinatal and infantile forms of HPP. However, treatment of those patients without life-threatening HPP is limited. This report describes the results of asfotase alfa (Strensiq (R), Alexion Pharmaceuticals, Inc.) treatment in a 6-year-old girl with childhood HPP, who presented with premature loss of primary teeth, low mobility, and chronic pain in the legs. Sequence analysis of the TNSALP gene revealed three heterozygous variants; c.526G>A (reported previously), c.1051G>C (novel), c.787T>C (reported previously). After a four-year follow-up under ERT, a marked reduction in leg pain and restlessness was observed and physical therapy assessments showed remarkable improvements in motor function, pain score, and quality of life. The treatment decision in childhood HPP is not as clear as in infantile and perinatal forms and it is mostly based on the clinical and radiological condition of the patient. In patients with childhood HPP without severe skeletal involvement but accompanying motor retardation, ERT may improve quality of life, motor functions, and daily activities

Investigation of the Relationship Between Fok1 and Col1A1 Gene Polymorphisms and Development of Treatment-Related Bone Complications in Children with Acute Lymphoblastic Leukemia

Objective: In acute lymphoblastic leukemia (ALL), various clinical risk factors and genetic predispositions contribute to the development of bone complications during and after chemotherapy. In this study, we aimed to investigate whether vitamin D receptor (VDR) Fok1 and collagen protein Col1A1 Sp1-binding site gene polymorphisms, which are important in bone mineral and matrix formation, have effects on the development of bone abnormalities in childhood ALL survivors

Early and late diagnoses of 17 beta-Hydroxysteroid dehydrogenase type-3 deficiency in two unrelated patients

17 beta-hydroxysteroid dehydrogenase type 3 deficiency is a rare cause of 46 XY disorders of sexual development. Mutations in the HSD17B3 gene result in reduced activity of the 17 beta-HSD3 enzyme, decreasing the conversion of androstenedione to testosterone. In this report, two cases, admitted with different clinical findings in the neonatal and adolescent periods and were decided to be raised in different genders are presented. The first case who had complete female external genitalia presented on the third postnatal day with the complaint of swelling in the groin. He was decided to be raised as a male and was treated successfully with parenteral testosterone in order to increase phallus size before surgical correction of the external genitalia. The second case was an adolescent girl who presented due to pubertal virilisation and primary amenorrhoea and chose female gender. Molecular genetic analyses of the HSD17B3 gene revealed two different previously reported homozygous variants. We emphasise that patients with 17 beta-hydroxysteroid dehydrogenase type 3 deficiency can present with heterogeneous clinical findings in different age groups. Early diagnosis is important to prevent future gender confusion and related problems

Evaluation of Turner Syndrome Knowledge among Physicians and Parents

Objective: Turner syndrome (TS) is one of the most common chromosomal abnormalities and an important cause of short stature and infertility due to ovarian failure in females. The aim was to evaluate the knowledge of TS among physicians and parents of children with TS and to enhance awareness about this subject

Effects of maternal folic acid supplementation on airway remodeling and allergic airway disease development

Objective: Maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy to reduce the risk of infant neural tube defects. However, an uncertain relationship between folic acid supplementation during pregnancy and development of childhood asthma exists. Recent data show a methyl donor-rich diet could increase the risk of developing allergic airway disease through DNA methylation and aberrant gene transcription. This study evaluated the effect of folic acid supplementation during pregnancy on airway remodeling and allergic airway disease vulnerability in a mouse asthma model.Methods: BALB/c mice were divided into four groups according to gestational folic acid supplementation and postnatal ovalbumin (OVA) exposure: Group 1 (whole pregnancy folic acid supplementation+OVA-exposed group), Group 2 (first gestational week folic acid supplementation+OVA-exposed group), Group 3 (no folic acid supplementation+OVA-exposed group), and Group 4 (control group). Offspring were sacrificed on day 45 for immunohistological and ultrastructural tests.Results: In OVA challenged groups, folic acid supplementation led to a thicker epithelial and subepithelial smooth muscle layer than in the unsupplemented group. Moreover, folic acid supplementation during whole pregnancy (Group 1) was associated with a thicker epithelial and subepithelial smooth muscle layer than folic acid supplementation during the first week of pregnancy (Group 2), suggesting a duration-response relationship. Electron microscopic imaging revealed that structural changes including the loss of epithelial integrity, thickening of basement membrane, and subepithelial fibrosis were more prominent in the folic acid supplementation groups.Conclusions: This study suggested that maternal folic acid supplementation during pregnancy affects airway remodeling and increases the allergic responses induced by ovalbumin challenge in offspring. In addition, the effect size increased as the duration and cumulative dose increased

Effects of maternal folic acid supplementation on airway remodeling and allergic airway disease development

Objective: Maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy to reduce the risk of infant neural tube defects. However, an uncertain relationship between folic acid supplementation during pregnancy and development of childhood asthma exists. Recent data show a methyl donor-rich diet could increase the risk of developing allergic airway disease through DNA methylation and aberrant gene transcription. This study evaluated the effect of folic acid supplementation during pregnancy on airway remodeling and allergic airway disease vulnerability in a mouse asthma model.Methods: BALB/c mice were divided into four groups according to gestational folic acid supplementation and postnatal ovalbumin (OVA) exposure: Group 1 (whole pregnancy folic acid supplementation+OVA-exposed group), Group 2 (first gestational week folic acid supplementation+OVA-exposed group), Group 3 (no folic acid supplementation+OVA-exposed group), and Group 4 (control group). Offspring were sacrificed on day 45 for immunohistological and ultrastructural tests.Results: In OVA challenged groups, folic acid supplementation led to a thicker epithelial and subepithelial smooth muscle layer than in the unsupplemented group. Moreover, folic acid supplementation during whole pregnancy (Group 1) was associated with a thicker epithelial and subepithelial smooth muscle layer than folic acid supplementation during the first week of pregnancy (Group 2), suggesting a duration-response relationship. Electron microscopic imaging revealed that structural changes including the loss of epithelial integrity, thickening of basement membrane, and subepithelial fibrosis were more prominent in the folic acid supplementation groups.Conclusions: This study suggested that maternal folic acid supplementation during pregnancy affects airway remodeling and increases the allergic responses induced by ovalbumin challenge in offspring. In addition, the effect size increased as the duration and cumulative dose increased