ABSTRACT
BACKGROUND: A transient dysfunction of the endocrine growth axis has been reported in celiac disease (CD). This apparent growth hormone deficiency (GHD) generally normalizes with the institution of a gluten-free diet (GFD). However, in few cases, the dysfunction of the GH axis persists despite a good adherence to the GFD. Aims of this study were to investigate pediatric patients with concurrent CD and GHD and to compare them with patients with isolated CD. METHODS: Data regarding CD patients with and without associated GHD were retrospectively collected. Inclusion criteria were availability of anthropometric and laboratory data at baseline and regularly at the reference center up to a 2-year follow-up. In case of poor catch-up growth despite a good adherence to the GFD, endocrinological investigation was carried on. RESULTS: Fifty-three patients with CD were included. Four (7.5%) out of 53 CD patients had a concurrent GHD. In two cases, firstly diagnosed with CD, GHD was suspected because of a poor catch-up growth despite a good adherence to the GFD. In two other cases, firstly diagnosed with GHD, gastrointestinal symptoms revealed the diagnosis of CD. Normalization of height velocity was achieved by GH treatment in all cases. No statistical significant difference between the two groups of patients was found as regard laboratory and histological features of CD. It is to note that 2 out of 4 patients with concomitant CD and GHD had thyroiditis compared to 6% of patients with isolated CD (P=0.004). CONCLUSIONS: A high prevalence of CD and GHD association was found. CD patients with poor catch-up growth despite a good adherence to the GFD should be carefully investigated for endocrine disorders.
Subject(s)
Celiac Disease/complications , Human Growth Hormone/deficiency , Celiac Disease/epidemiology , Child , Child, Preschool , Diet, Gluten-Free , Female , Growth Disorders/epidemiology , Humans , Male , Prevalence , Retrospective StudiesABSTRACT
BACKGROUND: Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. METHODS: A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. RESULTS: 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. CONCLUSIONS: The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/complications , Cystic Fibrosis/genetics , Mutation/genetics , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Female , Heterozygote , Homozygote , Humans , Infant , Italy , Male , Middle Aged , Phenotype , Retrospective Studies , Young AdultABSTRACT
Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management.
