Clinical trial NCT02870166: Genetic Study of Severe Zinc Deficiencies
Official title: Genetic Study Explanatory Severe Zinc Deficiencies : Multicenter, Genetics, Controlled and Prospective Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acrodermatitis Enteropathica
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2016-08-17
Enrollment: 96
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The investigators had therefore selected 96 individuals for the project. They correspond either to the patients themselves (ie the index case tested in the laboratory) or to mothers and / or fathers of patients who accompany their child consultation. For each of them, the analysis will focus on the genomic DNA was extracted from peripheral blood leukocytes and is stored in the sample bank of DNA laboratory. Note that twenty patients seen by our collaborator neurologist, Prof. Vincent Ramaekers (Belgium) are a subgroup separately in our study, since all have autistic disorders responsive to the zinc, in addition to zinc deficiency. By studying these patients in particular clinical picture, we already approach the possible consequences of zinc deficiency on complex diseases.

Brief summary: Given the structural essential, catalytic and co-catalytic played by zinc in many sections of protein metabolism, carbohydrate and lipid (zinc is involved in the function of more than 300 metalloenzymes and metalloproteins), one can imagine the impact of a deficiency or even a sub-chronic zinc deficiency on the health of the individual. Studies multiply that show that, long-term, marginal zinc deficiency is a risk factor for the development of cancer or neurodegenerative complex diseases (eg Alzheimer's disease). In addition, the short-term zinc deficiencies foster the development of skin conditions and susceptibility to viral and bacterial infections. The aim of this project is to identify, in the population of patients with pseudo-acrodermatitis enteropathica (AE) tested in the investigators laboratory, rare variants (mutations "real" epimutations or polymorphisms) located in solute carrier family 39 member 4 (SLC39A4) gene or in 55 other genes chosen for their role in zinc homeostasis.


Eligibility criteria: Inclusion Criteria:

* Are included all patients (minors included) with suggestive symptoms and biological signs of a hereditary deficiency of zinc, appeared for the first time at birth or weaning (see description given in the introduction);
* Clinical diagnosis of zinc deficiency must be made by a specialist dermatologist, pediatrician or gastroenterologist;
* Zinc deficiency has been audited by an assay of serum zinc, erythrocyte, plasma, urine or hair;
* The response of all symptoms and signs to zinc oral supplementation should be rapid and complete.

Exclusion Criteria:

* All patients with homozygous or compound heterozygous mutations in the SLC39A4 gene are excluded because they have a proven acrodermatitis enteropathica (AE);
* All patients who developed their first symptoms of zinc deficiency outside the neonatal period, most likely because they have an acquired deficiency and not congenital;
* All patients with probable cause of zinc deficiency that is surgery of the digestive tract, chronic digestive disease, or total parenteral nutrition.

Primary outcomes:
measure: Homozygous mutations in the SLC39A4 gene
timeFrame: at 3 years
measure: heterozygous mutations in the SLC39A4 gene
timeFrame: at 3 years
measure: deleterious variants in 55 zinc homeostasis genes in patient
timeFrame: at 3 years
measure: deleterious variants in 55 zinc homeostasis genes in patient's parents
timeFrame: at 3 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Nantes University Hospital
name: Stephane BEZIEAU, PU-PH
role: PRINCIPAL_INVESTIGATOR
References: