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.

CASE PRESENTATION:

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.

CONCLUSION:

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: Cristina Maria Mihai, Doina Catrinoiu, Marius Toringhibel, Ramona Mihaela Stoicescu, Negreanu-Pirjol Ticuta, Hancu Anca
• Journal: Cases journal (Cases J) Vol. 2 Issue 1 Pg. 19 (Jan 07 2009) ISSN: 1757-1626 [Electronic] England
• PMID: 19128470 (Publication Type: Journal Article)