Genetic Newborn Screening for Cystinosis and Spinal Muscular Atrophy

NCT06027385 | Completed

• 1 other identifier: 2017-GEN1
• Study Type: interventional
• Target: 300,000
• Locations: 1 country
• Sites: 4

Brief Summary

Newborn screening in Germany is a voluntary program. Cystinosis and spinal muscular atrophy (SMA) are rare autosomal recessive diseases. They are inherited in an autosomal recessive manner, i.e. both parents carry a defective gene. Neither disease can be detected early by the methods established in routine newborn screening. However, common genetic mutations are known for both diseases. The aim of the study presented here is to provide the scientific basis for molecular genetic newborn screening for cystinosis and SMA. In particular, to investigate whether inclusion of these diseases in general newborn screening should be recommended. The participating screening laboratories for this project are Labor Becker \& Kollegen, Munich, Germany and Screening Laboratory Hannover, Germany. Hospitals that send their dry blood spot cards for routine newborn screening to these laboratories will receive an offer to participate in the pilot project. Participation is free of charge. Parents who wish to participate in this pilot project will receive an information sheet explaining the screening process and objectives. A parent and the treating physician sign the information sheet as documentation of informed consent. Their signature and informed consent are required for the pilot. Routine NBS according to German pediatric guidelines involves the collection of dried blood spot cards 36-72 hours after birth. Molecular genetic screening in the pilot project will be performed with the same dried blood spot card used for routine newborn screening. In cystinosis, genetic testing for the 3 most common mutations in Germany will be performed. In SMA, a homozygous deletion of exon 7 in the SMN gene is detected by a PCR test. The molecular genetic test is performed on the same day as routine newborn screening.Normal findings are not reported to parents. However, they can contact the laboratories to inquire about them. Parents of newborns with two mutations in the cystinosis gene or with a homozygous deletion of exon 7 in the SMN gene are immediately informed of the disease by a physician. Further diagnostics to confirm the disease will be organized close to home. The study started on Jan. 15, 2018, and recruitment was completed on Sept. 30, 2022.

Conditions

Cystinosis; Cystinosis, Nephropathic; Spinal Muscular Atrophy

Keywords

Newborn Screening; Screening; Molecular-based Screening

Outcome Measures

Primary Outcomes (4)

• Number of participants with confirmed diagnosis of Cystinosis

  Newborns identified with 57-kb CTNS mutation homozygous, compound heterozygous , with c.18\_21delGACT p.T7Ffs\*7 homozygous or compound heterozygous or c.926\_927insG, p.S310Qfs \* 55 homozygous or compound heterozygous and elevated white blood cell cystine level.

  up to 60 months

• Number of participants with heterozygous mutations

  Newborns identified with heterozygous CTNS mutations of 57-kb CTNS and heterozygous c.18\_21delGACT p.T7Ffs\*7 mutations and heterozygous c.926\_927insG, p.S310Qfs \* 55 mutations

  up to 4 weeks

• Number of participants with confirmed diagnosis of SMA

  Newborns identified with homozygous deletion of exon 7 in the SMN1-gene

  up to 48 months

• time interval until start of treatment for both diseases

  For both diseases the time interval will be evaluated from the time of identification in screening to the introduction of therapy.

  up to 4 weeks

Study Arms (1)

Tested Newborns

EXPERIMENTAL

Tested for three mutations in the CTNS gene and one mutation in the SMN1 gene.

Diagnostic Test: molecular-based screening

Interventions

molecular-based screening DIAGNOSTIC_TEST

Test for three mutations in the CTNS gene and one mutation in the SMA1 gene.

Tested Newborns

Eligibility Criteria

• Age: 36 Hours - 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newborns whose dry bloodspot card was sent to screening labs involved in the project
• Consent of guardians

You may not qualify if:

• no consent of guardians

Sponsors & Collaborators

• Cystinose Stiftung: lead
• Labor Becker & Kollegen, Munich, Germany: collaborator
• Screening Labor Hannover: collaborator
• Genetikum, Ulm, Germany: collaborator
• Bavarian State Office of Health and Food Safety (LGL), Unterschleißheim, Germany: collaborator
• Internal Medicine, Freiburg University Hospital, Freiburg, Germany: collaborator
• Attorney DSZ Rechtsanwälte GmbH, Barkhovenallee 1, 45239 Essen: collaborator

Study Sites (4)

RoMed Hospital

Rosenheim, Bavaria, 83022, Germany

Location

University Hospital Essen, Center for Pediatrics and Adolescent Medicine

Essen, 45122, Germany

Location

Dr. von Haunersches Kinderspital

München, 80337, Germany

Location

University Hospital Münster, Clinic and Polyclinic for Pediatrics and Adolescent Medicine

Münster, 48149, Germany

Location

Related Publications (6)

• Hohenfellner K, Elenberg E, Ariceta G, Nesterova G, Soliman NA, Topaloglu R. Newborn Screening: Review of its Impact for Cystinosis. Cells. 2022 Mar 25;11(7):1109. doi: 10.3390/cells11071109.

  PMID: 35406673 BACKGROUND

• Vill K, Blaschek A, Schara U, Kolbel H, Hohenfellner K, Harms E, Olgemoller B, Walter MC, Muller-Felber W. [Spinal muscular atrophy : Time for newborn screening?]. Nervenarzt. 2017 Dec;88(12):1358-1366. doi: 10.1007/s00115-017-0447-3. German.

  PMID: 29101527 BACKGROUND

• Hohenfellner K, Bergmann C, Fleige T, Janzen N, Burggraf S, Olgemoller B, Gahl WA, Czibere L, Froschauer S, Roschinger W, Vill K, Harms E, Nennstiel U. Molecular based newborn screening in Germany: Follow-up for cystinosis. Mol Genet Metab Rep. 2019 Sep 18;21:100514. doi: 10.1016/j.ymgmr.2019.100514. eCollection 2019 Dec.

  PMID: 31641587 BACKGROUND

• Fleige T, Burggraf S, Czibere L, Haring J, Gluck B, Keitel LM, Landt O, Harms E, Hohenfellner K, Durner J, Roschinger W, Becker M. Next generation sequencing as second-tier test in high-throughput newborn screening for nephropathic cystinosis. Eur J Hum Genet. 2020 Feb;28(2):193-201. doi: 10.1038/s41431-019-0521-3. Epub 2019 Sep 30.

  PMID: 31570786 BACKGROUND

• Vill K, Kolbel H, Schwartz O, Blaschek A, Olgemoller B, Harms E, Burggraf S, Roschinger W, Durner J, Glaser D, Nennstiel U, Wirth B, Schara U, Jensen B, Becker M, Hohenfellner K, Muller-Felber W. One Year of Newborn Screening for SMA - Results of a German Pilot Project. J Neuromuscul Dis. 2019;6(4):503-515. doi: 10.3233/JND-190428.

  PMID: 31594245 BACKGROUND

• Czibere L, Burggraf S, Fleige T, Gluck B, Keitel LM, Landt O, Durner J, Roschinger W, Hohenfellner K, Wirth B, Muller-Felber W, Vill K, Becker M. High-throughput genetic newborn screening for spinal muscular atrophy by rapid nucleic acid extraction from dried blood spots and 384-well qPCR. Eur J Hum Genet. 2020 Jan;28(1):23-30. doi: 10.1038/s41431-019-0476-4. Epub 2019 Jul 30.

  PMID: 31363188 BACKGROUND

MeSH Terms

Conditions

Cystinosis; Muscular Atrophy, Spinal

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Officials

• Katharina Hohenfellner, PD Dr.

  RoMed Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All newborns whose parents have agreed to participate in the pilot project will be tested for three mutations in the CTNS gene and a homozygous deletion of exon 7 in the SMN1-gene.

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: September 7, 2023
• Study Start: January 15, 2018
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: September 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)