Mitochondrial Membrane Protein Neurodegeneration (MPAN)

The Effect of 6-week Rehabilitation Program in Brothers With MPAN: A Report of Two Cases.

The purpose of this case study was to investigate the effects of therapeutic intervention in 9- and 12-year-old brothers with MPAN. The main hypothesis it aims to answer is:

-A 6-week balance and coordination focused rehabilitation program improves independence and gait parameters in patients with MPAN.

Study Overview

• Status: Completed
• Conditions: MPAN
• Intervention / Treatment: Other: Passive Stretching; Other: Mobilization; Other: Muscle strengthening; Other: Balance and Coordination

Detailed Description

Neurodegeneration with brain iron accumulation (NBIA) comprises a heterogeneous group of disorders with accumulation of iron in the brain, mostly basal ganglia. Mutations within C19orf12 have recently been identified in patients with NBIA. This C19orf12 gene -located in mitochondria and endoplasmic reticulum- encodes a mitochondrial membrane protein and the abbreviation MPAN. Pathogenic mutations in this gene are postulated to cause dysfunction of lipid homeostasis in mitochondria.

Patients with MPAN typically present with gait disturbance due to lower limb spasticity and dystonia, parkinsonism with subsequent spastic paresis, dysarthria, cerebellar ataxia, behavioral problems, dementia, psychomotor delay, peripheral neuropathy, visual changes like optic atrophy as well as bowel/bladder incontinence; however, MPAN has a greater variability compared with other NBIA cases in terms of age of onset (age three to 30 years) and speed of progression.

This study aims to investigate the effects of therapeutic intervention in male brothers, age 9 and 12, with MPAN. In particular, this study tested the following hypotheses after 6 weeks of rehabilitation by measuring muscle strength, muscle tone, range of motion , balance and coordination: (1) After the training period, muscle strenght, muscle tone and range of motion would be improved, (2) these developments in body function can lead to increase balance and coordination, and (3) due to the these improvements, functional independency may increase.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Kırşehir, Turkey
    • Ahi Evran University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 14 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Being diagnosed with MPAN

Exclusion Criteria:

• being involved in any other rehabilitation program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Balance and Coordination; Since it is a case study, there will be only one group in the study.

Other: Passive Stretching; Sustained passive stretching of hamstring, tendo-achilles, and adductors 10 (30 s, with three repetitions, five times per week); Other: Mobilization; Grade four mobilizations is a stretching motion performed at the talocrural joint with anterior-posterior gliding. Mobilization was performed once a day, 6 times a day, and 5 times a week, only on both deformed feet of the older sibling; Other: Muscle strengthening; Abdominal muscle strengthening exercises were given to both siblings once a day, 10 times a day, 5 times a week. In the supine position, the patients were asked to lie on their knees with the knees flexed. The hip extensors were trained in the prone position on the bed by resisting hip extension; Other: Balance and Coordination; The following exercises were applied 5 times a week, with 1o repetition once a day.; Standing on one leg in front of the mirror,; Tandem walking,; Rhythmic Dynamic Stabilization,; Swiss ball sitting (eyes open and closed),; Counting the alphabet or numbers while marching

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Balance	Balance and coordination will be evaluated with the Pediatric Berg Balance Test.	6 weeks
Functional İndependence	Functional independence which will evaluate with Functional Independence Measure for Children (WeeFIM).	6 weeks
Observational Gait Analysis	Gait characteristic will assessed with Observational Gait Analysis (OGA).	6 weeks

Collaborators and Investigators

• Sponsor: Kirsehir Ahi Evran Universitesi
• Investigators: Study Director: Figen TUNCAY, Kirsehir Ahi Evran Universitesi

Publications and helpful links

General Publications

• Ramesh R, Deenadayalu A, Bhattacharjee S, Paramanandam V. C19orf12 mutation causing mitochondrial membrane-protein Associated Neurodegeneration masquerading as spastic paraplegia. Parkinsonism Relat Disord. 2021 Aug;89:146-147. doi: 10.1016/j.parkreldis.2021.07.014. Epub 2021 Jul 13.
• Yang Y, Zhang S, Yang W, Wei T, Hao W, Cheng T, Wang J, Dong W, Qian N. Case Report: Identification of a De novo C19orf12 Variant in a Patient With Mitochondrial Membrane Protein-Associated Neurodegeneration. Front Genet. 2022 Mar 30;13:852374. doi: 10.3389/fgene.2022.852374. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Actual): September 28, 2023
• Study Completion (Actual): September 28, 2023

Study Registration Dates

• First Submitted: December 22, 2022
• First Submitted That Met QC Criteria: January 7, 2023
• First Posted (Actual): January 10, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Exercise Therapy; MPAN; Balance and Coordination
• Other Study ID Numbers: AEvran

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data can be shared online if requested.
• IPD Sharing Time Frame: 6 months study finished
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No