Peripheral Serotonin and Albinism (SEPIAs)

Assistance Publique - Hôpitaux de Paris

Status: Enrolling

Conditions: Oculocutaneous Albinism

Treatments: Other: Dosage of serotonin and metabolites; Other: Blood parameters

Study type: Observational

Funder types: Other

Identifiers

NCT06138509

2023-A01431-44 (Other Identifier)

APHP230808

Details and patient eligibility

About

Serotonin (5-HT or 5-hydroxytryptamine) is a monoamine primarily known for its role as a neurotransmitter in the central nervous system (CNS). However, the functions of serotonin go beyond its role in the central nervous system: different peripheral tissues have the capacity to produce and/or use serotonin locally, forming systems called "micro-serotonergic" systems. Among the peripheral roles of serotonin, previous work by the Iron and Immunity team, INSERM U1016, Institut Cochin (Paris), was able to show that serotonin has a positive role on erythropoiesis and the survival of red blood cells, and the team's ongoing work suggests that serotonin also impacts iron metabolism.

In humans and in mouse models, several studies have suggested a role for serotonin in pigmentation. In certain syndromic forms of albinism such as Hermansky Pudlak syndrome, platelet serotonin levels are reduced in connection with a decrease in dense platelet granules (delta granules): this characteristic is even part of the diagnostic criteria.

Preliminary data from the Iron and Immunity team found:

• Changes in serotonin levels in children with albinism compared to control patients,
• Changes in hemoglobin level and mean corpuscular volume (MCV) in children with albinism (towards anemia and microcytosis),
• Changes in the iron balance in children with albinism (towards iron deficiency).

The hypothesis of this research is that peripheral serotonin plays a role in the clinical and biological manifestations of oculocutaneous albinism.

Full description

Serotonin (5-HT or 5-hydroxytryptamine) is a monoamine primarily known for its role as a neurotransmitter in the central nervous system (CNS). However, the functions of serotonin go beyond its role in the central nervous system: different peripheral tissues have the capacity to produce and/or use serotonin locally, forming systems called "micro-serotonergic" systems. Among the peripheral roles of serotonin, previous work by the Iron and Immunity team, INSERM U1016, Institut Cochin (Paris), was able to show that serotonin has a positive role on erythropoiesis and the survival of red blood cells, and the team's ongoing work suggests that serotonin also impacts iron metabolism.

Albinism exhibits significant clinical and genetic heterogeneity with poor genotype-phenotype correlation, and nearly 15% of patients remain without a molecular diagnosis. There is no curative treatment for albinism. Patients with albinism suffer from physical disability throughout their lives, but can also suffer from psychological disability and discrimination. These patients are also more vulnerable to the effects of climate change. The unmet clinical needs are therefore enormous.

In humans and in mouse models, several studies have suggested an unexpected role for serotonin in skin pigmentation at several levels. Transcriptomic studies revealed that the Tph1 gene, responsible for serotonin synthesis outside the CNS, as well as serotonin receptors, were expressed in melanocytic and keratinocytic cell lines. Other studies have indicated that serotonin enhances melanogenesis in three melanocyte cell lines (B16F10, SK-MEL-2, Melan-a). Finally, studies suggest that serotonin is involved in pathologies such as certain congenital dyschromias, Rett syndrome and vitiligo. In certain syndromic forms of albinism such as Hermansky Pudlak syndrome, platelet serotonin levels are reduced in connection with a decrease in dense platelet granules (delta granules): this characteristic is even part of the diagnostic criteria.

Preliminary data from the Iron and Immunity team found:

• Changes in serotonin levels in children with albinism compared to control patients,
• Changes in hemoglobin level and mean corpuscular volume (MCV) in children with albinism (towards anemia and microcytosis),
• Changes in the iron balance in children with albinism (towards iron deficiency).

The hypothesis of this research is that peripheral serotonin plays a role in the clinical and biological manifestations of oculocutaneous albinism.

The study will assess serotonin and its metabolites in the serum of patients with albinism, and compare the results with controls patients. The level of serotonin and its metabolites will be correlated with the different genotypes, and with the severity of albinism within the same genotypes.

This study also wish to explore the impact of serotonin levels in the development of anemia, microcytosis and/or iron deficiency in patients with albinism. Complete blood counts and iron studies in patients with albinism will be compare to those of control patients too.

Enrollment: 160 estimated patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients:

• Patients with albinism aged 2 to 17 years
• Followed in the MAGEC-Necker reference center (reference center for rare diseases of the skin and mucous membranes of genetic origin), during the inclusion period
• Information of parental authority holders of patients and patients of understanding age, and collection of consent from parental authority holders and patients.

Controls:

• Patients aged 2 to 17 years old
• Having consulted in Necker hospital during the inclusion period in the emergency and surgical services and whose care required a blood test analyzed in the hematology laboratory of the Necker hospital.
• Normal complete blood count (CBC)
• Normal C-reactive protein test (CRP)
• Absence of opposition from parental authority holders within one month of after sending the study information note.

Exclusion criteria

Patients:

- Inability to have a blood test

Controls:

• Abnormal blood count
• Elevation of CRP above laboratory standard

Trial design

160 participants in 2 patient groups

Patients

Description:

Patients with albinism aged 2 to 17 years old and followed in the MAGEC-Necker reference center (reference center for rare diseases of the skin and mucous membranes of genetic origin), during the inclusion period. During an initial or a follow-up consultation for patients with albinism, an additional volume of blood will be drawn during a blood sample drawn as part of routine care.

Treatment:

Other: Blood parameters

Other: Dosage of serotonin and metabolites

Control patients

Description:

Control patients are patients who were seen at Necker-Enfants Malades Hospital during the inclusion period, in the emergency and surgical departments, and whose care required a blood test analyzed in the Necker-Enfants Malades Hospital hematology laboratory. These patients will be selected on their age (2 to 17 years old), and must have a normal complete blood count and CRP. Leftover blood not used by the hospital hematology laboratory will be used for study analyses.

Treatment:

Other: Blood parameters

Other: Dosage of serotonin and metabolites