Genetic Study of Severe Zinc Deficiencies (GENEZINC)

Genetic Study Explanatory Severe Zinc Deficiencies : Multicenter, Genetics, Controlled and Prospective Study

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.

Study Overview

• Status: Completed
• Conditions: Acrodermatitis Enteropathica
• Intervention / Treatment: Other: blood sample

• Study Type: Observational
• Enrollment (Actual): 96

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • CHU de Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Homozygous mutations in the SLC39A4 gene	at 3 years
heterozygous mutations in the SLC39A4 gene	at 3 years
deleterious variants in 55 zinc homeostasis genes in patient	at 3 years
deleterious variants in 55 zinc homeostasis genes in patient's parents	at 3 years

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Stephane BEZIEAU, PU-PH, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: August 12, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (Estimated): August 17, 2016

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Dermatitis; Skin Abnormalities; Acrodermatitis enteropathica; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: RC12_0193