Impaired IGF1-GH axis and new therapeutic options in Alström Syndrome patients: a case series

• Published in: Cases journal Vol. 2; no. 1; p. 19
• Main Authors: Mihai, Cristina Maria, Catrinoiu, Doina, Toringhibel, Marius, Stoicescu, Ramona Mihaela, Ticuta, Negreanu-Pirjol, Anca, Hancu
• Format: Journal Article
• Language: English
• Published: England Cases Network Ltd 07.01.2009; BioMed Central Ltd; BioMed Central
• Subjects: Care and treatment; Case Report; Case studies; Complications and side effects; Diagnosis; Genetic disorders; Health aspects; Insulin-like growth factor 1; Somatotropin; Romania
• ISSN: 1757-1626; 1757-1626
• DOI: 10.1186/1757-1626-2-19

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. 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. 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.