Mauriac Syndrome: Isotopic Techniques and Genetic Analysis

University of Lausanne (UNIL)

Status: Completed

Conditions: Glycogen Deposition; Diabetes Mellitus; Short Stature

Treatments: Other: oral glucose load; Other: exercise test

Study type: Interventional

Funder types: Other

Identifiers

NCT04275141

NCT2019-01755

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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6 participants in 2 patient groups

Mauriac syndrome

Other group

Description:

An oral dose of glucose (labelled with 1% U-13C6-glucose) will be given at time 0 min followed by a 30-min cycling exercise at time 300 min.

Treatment:

Other: oral glucose load

Other: exercise test

Type 1 diabetes mellitus

Other group

Description:

An oral dose of glucose (labelled with 1% U-13C6-glucose) will be given at time 0 min followed by a 30-min cycling exercise at time 300 min.

Treatment:

Other: oral glucose load

Other: exercise test