title: Impaired IGF1-GH axis and new therapeutic options in Alström Syndrome patients: a case series.
abstract: BACKGROUND
  Defects of the primary cilium and its anchoring structure, the basal body, cause a number of human genetic disorders, collectively termed ciliopathies: primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.Alström syndrome is an extremely rare, autosomal recessive genetic disorder characterized by a group of signs and symptoms including infantile onset dilated cardiomyopathy, blindness, hearing impairment/loss, obesity, diabetes, hepatic and renal dysfunction.Because adult growth hormone deficiency and Alström Syndrome share some clinical and metabolic features, we studied the GH-IGF1 axis, using MRI techniques and dynamic tests in 3 unrelated patients with Alström syndrome.
  
  
  METHODS
  The patients were hospitalized and the growth hormone stimulatory tests were made, as well as brain MRI. Insulin provocative test revealed a severe GH deficiency in these patients, defined by a peak response to insulin-induced hypoglycemia less than 3 ng/dl and IGF1 concentrations less than - 2SDS.We didn't find multiple pituitary hormone deficiency and we noticed only a severe GH deficiency in all three patients. The MRI study of the diencephalic and pituitary region was suggestive for the diagnosis of empty sella in one patient.One patient received Recombinant-GH replacement for one year with very good results, one underwent a gastric sleeve with a satisfactory outcome, one patient died due to the progression of the cardiac myopathy.
  
  
  CONCLUSIONS
  Future studies are needed to assses if the substitution therapy with Recombinant Growth hormone is cost-effective and without risk in such patients with Alström Syndrome and severe insulin resistance, despite our good results in one patient. Also, careful clinical and genetic studies can contribute to a better understanding of the evolution after different therapeutical attempt in the complex disorders such as Alström Syndrome.
authors.affiliation: "Ovidius" University Constanta, Faculty of Medicine, Constanta County Emergency Hospital, 145 Tomis Blvd, 900591, Constanta, Romania. cristina2603@yahoo.com.
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Mihai
authors.forename: Doina
authors.initials: D
authors.lastname: Catrinoiu
authors.forename: Marius
authors.initials: M
authors.lastname: Toringhibel
authors.forename: Ramona Mihaela
authors.initials: RM
authors.lastname: Stoicescu
authors.forename: Negreanu-Pirjol
authors.initials: NP
authors.lastname: Ticuta
authors.forename: Hancu
authors.initials: H
authors.lastname: Anca