Neonatal Screening of Biotinidase Deficiency: Genotype-phenotype Correlation and Clinical Follow-up

Neonatal Screening of Biotinidase Deficiency: Genotype-phenotype Correlation and Clinical Follow-up of Patients Identified at the Regional Centre for Neonatal Screening of Endocrine-Metabolic Diseases in Bologna

Retro-prospective, single-centre, observational study conducted at the Endocrine-Metabolic Diseases Center of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

The study involves children born in Emilia-Romagna region, Italy, from January 2016 to December 2020 with biotinidase deficiency identified through Neontal Screening at the Endocrine-Metabolic Diseases Center of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy. The primary aim of this study is to assess the incidence of biotinidase decificiency in this cohort of patients and the possible correlation between the genotype and the biochemical and clinical phenotype of this cohort of patients.

Study Overview

• Status: Recruiting
• Conditions: Biotinidase Deficiency

Detailed Description

The study consists of the retrospective collection and analysis of clinical, biochemical and genetic data of pediatric patients who were taken in charge for Biotinidase Deficiency at the Endocrine-Metabolic Diseases Center of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy, following Neonatal Screening positivity.

For this cohort of patients, a clinical evaluation is planned annually after the diagnosis of Biotinidase Deficiency for the identification of possible long-term complications. A clinical follow-up of at least 36 months is expected.

According to clinical practice, parents of pediatric patients with Biotinidase Deficiency identified through Neonatal Screening will undergo molecular genetic analysis for specific familial mutations of the BTD gene, but will not be followed up.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Rita Ortolano, MD; Phone Number: 00390512144816; Email: rita.ortolano@aosp.bo.it

Study Locations

• Italy
  • Bologna
    • Bologna, Bologna, Italy, 40138
      • Recruiting
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna
      • Contact: Rita Ortolano, MD; Phone Number: 00390512144816; Email: rita.ortolano@aosp.bo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients with Biotinidase Deficiency (and their parents) identified through Neonatal Screening from January 2016 to December 2020 at the Endocrine-Metabolic Diseases Center of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy.

Description

INCLUSION CRITERIA:

FOR PEDIATRIC PATIENTS

• Neonatal Screening test result of Residual biotinidase Enzyme Activity <50% carried out from January 2016 to December 2019 at the Endocrine-Metabolic Diseases Center of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy;
• Neonatal Screening test result of Residual biotinidase Enzyme Activity <30% carried out from January 2020 to December 2020 at the Endocrine-Metabolic Diseases Center of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy;
• Obtaining informed consent from parents or legal guardian of pediatric patients.

FOR PARENTS

• Being a parent of a paediatric patient enrolled in the study;
• Availability of parental data;
• Obtaining informed consent.

EXCLUSION CRITERIA:

• Subjects with known chromosomal abnormalities or complex syndromes.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BTD gene mutation	allele1, allele2 mutations	baseline
Residual biotinidase Enzymatic Activity	percentage %	baseline
Biotin replacement therapy	mg/die	baseline
Presence of Sintomatology	ocular, dermatological, neuropsychiatric symptoms	annually after the diagnosis of Biotinidase Deficiency up to 3 yaers

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Rita Ortolano, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Biotinidase Deficiency
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Amino Acid Metabolism, Inborn Errors; Multiple Carboxylase Deficiency; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Biotinidase Deficiency
• Other Study ID Numbers: BiotiPed

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No