Abstract
BackgroundDefects 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 presentationThe 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.ConclusionFuture 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.
Highlights
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
Considering that hypothalamic ciliary neuronal dysfunction is implicated in the etiology of obesity in Alström syndrome patients, we studied the presence of GH deficiency in our patients, because we assume that an early preventive intervention in such patients is GH replacement
We studied the GH-IGF1 axis, using MRI techniques and dynamic tests: GH 1- 0.32 ng/mL, GH 20.24 ng/mL, insulin-like growth factor-1 (IGF-1) 162 ng/mL (Normal: 220–972)
Summary
This case series showed that adolescents and adults with Alström syndrome have GH deficiency, and recombinant GH therapy might have beneficial effects on body composition, and insulin resistance, with improvement of the glucose homeostasis and cardiac function. Http://www.casesjournal.com/content/2/1/19 netic resonance imaging; SDS: standard deviation; MPHD: multiple pituitary hormone deficiency; ALMS1Alström syndrome 1(the gene responsible for Alström Syndrome); DKA: diabetic keto-acidosis; TSH: Thyroid Stimulating Hormone; fT3: free triiodothyronine; fT4: free thyroxine; DEXA: Dual energy X-ray absorptiometry; BMI: body mass index; BMD: bone mineral density; ITT: insulin tolerance test; SNP: single nucleotide polymorphism; BBS5: Bardet-Biedl Syndrome 5 (a human gene); GIR: glucose-to-insulin ratio; Re-GH: recombinant growth hormone; ALS: acid labile subunit; DCM-dilated cardiomyopathy. A copy of the written consent is available for review by the Editor-in-Chief of this journal
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