Clinical trial NCT04275141: Mauriac Syndrome: Isotopic Techniques and Genetic Analysis
Official title: Genetic Analysis Coupled to Application of Isotopic Techniques to the Study of Mauriac Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus
Short Stature
Glycogen Deposition
Lead sponsor: University of Lausanne
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
First posted: 2020-02-19
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Case control study
Primary purpose: OTHER

Brief summary: Mauriac syndrome (MS) is an entity of individuals combining poorly controlled diabetes mellitus type 1, short stature and glycogenic hepatopathy. Thus, the functional significance of Mauriac syndrome for glucose metabolism remains disputed, and whether genetic defects in glycogen metabolism contribute to glycogenic hepatopathy in MS remains to be clarified.Coupling the genetic analysis of targeted genes involved in glucose regulation with a dynamic exploration will eventually determine if a genetic abnormality leads to the disease and explains the nature of the phenotype.

Detailed description: Investigation of glucose homeostasis in MS, after an oral glucose load followed by exercise, using a quantitative measurement of the substrate flux. This dynamic in vivo kinetics can be explored using stable, nonradioactive tracers with the help of gas or liquid chromatography.

Investigation of genetic factors associated with MS phenotype. Molecular analysis will be performed by next generation sequencing (exome or whole genome sequencing). In addition, a targeted analysis for pathogenic variants in genes implicated in homeostasis regulation will be done.

Eligibility criteria: Inclusion Criteria:

* Inclusion criteria for controls:
* DT1
* \> 18 years old)
* Presence of at least one of the following auto-antibodies: anti-GAD65, anti-IAA, anti-ZnT8, anti-IA2 or ICA and/or low C-Peptide
* Insulin therapy by multiple daily injections or continuous subcutaneous insulin infusion by an insulin pump
* Informed consent as documented by signature

Inclusion criteria for subjects:

* Mauriac syndrome
* DT1
* \> 18 years old
* Presence of hepatomegaly in infancy (confirmed ≥ 1 abdominal US) at the time of diagnosis of Mauriac Syndrome
* Presence of short stature during infancy at the time of diagnosis of Mauriac Syndrome (\<P3; WHO growth curves on ≥ 2 different measures, at 2 different time-points)
* Presence of at least one of the following auto-antibodies: anti-GAD65, anti-IAA, anti-ZnT8, anti-IA2 or ICA and/or low C-Peptide
* Informed consent as documented by signature

Exclusion criteria for subjects and controls :

* Obesity (BMI ≥ 30 kg/m2 or \> 90th percentile)
* Illness that contraindicates physical activity
* Women who are pregnant or breast feeding
* Any clinically unstable disease
* Myocardial infarcts, syncope, heart rhythm disorder, unstable hypertension in the last 6 months
* Blood donation in the last 3 months for men and 4 months for women before the study
* Enrollment in a previous study less than 30 days before the start of the study
* Participation of the investigator, a family member, an employee or someone having a link with the investigator

Primary outcomes:
measure: In vivo kinetics of ingested glucose
timeFrame: Time -90 minutes to Time 360 minutes
measure: In vivo kinetics of endogenous glucose
timeFrame: Time -90 minutes to Time 360 minutes
measure: In vivo kinetics of lactate
timeFrame: Time -90 minutes to Time 360 minutes
Secondary outcomes:
measure: DNA Banking
timeFrame: At inclusion period
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Lausanne University Hospitals
state: Vaud
city: Geneva
country: Switzerland
facility: Geneva University Hospital
Study officials:
References: