Inclusion Criteria: 1. Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local Institutional Review Board (IRB)/independent ethics committee (IEC) approved consent. Informed assent will be sought from capable participants, in accordance with the directive of the IRB/IEC and with local requirements. 2. Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, participant assent. 3. Active CALD as defined by: 1. Elevated very long chain fatty acids (VLCFA) values, and 2. Active central nervous system (CNS) disease established by central radiographic review of brain MRI demonstrating: i) Loes score between 0.5 and 9 (inclusive) on the 34-point scale, and ii) Gadolinium enhancement (GdE) on MRI of demyelinating lesions. 4. NFS \< or = 1. Exclusion Criteria: 1. Prior receipt of an allogeneic transplant or gene therapy. 2. Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA levels. Note: participants must discontinue use of these medications at time of consent. 3. Receipt of an investigational study drug or procedure within 3 months before Screening that might confound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study. 4. Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents). 5. Hematological compromise as evidenced by: 1. Peripheral blood absolute neutrophil count (ANC) count \<1500 cells/ cubic millimeter (mm\^3), and either 2. Platelet count \<100,000 cells/mm\^3, or 3. Hemoglobin \<10 gram per deciliter (g/dL). 6. Hepatic compromise as evidenced by: 1. Aspartate transaminase (AST) value greater than (\>) 2.5 × upper limit of normal (ULN) 2. Alanine transaminase (ALT) value \>2.5 × ULN 3. Total bilirubin value \>3.0 milligram per deciliter (mg/dL), except if there is a diagnosis of Gilbert's Syndrome and the participant is otherwise stable 7. Baseline estimated glomerular filtration rate \<70 milliliter per minute (mL/min)/1.73 square meter (m\^2). 8. Cardiac compromise as evidenced by left ventricular ejection fraction \<40 percent (%). 9. Immediate family member with a known or suspected Familial Cancer Syndrome. 10. Clinically significant uncontrolled, active bacterial, viral, fungal, parasitic, or prion associated infection. 11. Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B virus (HBV); hepatitis C virus (HCV); human T lymphotrophic virus 1 (HTLV-1). (Note that participants who have been vaccinated against HBV \[positive for HBV surface antibodies\] who are negative for other markers of prior HBV infection \[e.g., negative for HBV core Ab\] are eligible. Participants with past exposure to HBV \[hepatitis B core antibody \[HBcAb\] -positive and/or hepatitis B e-antigen antibody \[HBeAb\]-positive\] are also eligible for the study provided they have a negative test for HBV DNA. Also note that participants who are positive for anti-hepatitis C Ab are eligible as long as they have a negative hepatitis C viral load). 12. Any clinically significant cardiovascular, hematological, or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures. 13. Absence of adequate contraception for fertile participants. 14. Any contraindications to the use of Granulocyte colony-stimulating factor (G-CSF) or plerixafor during the mobilization of HSCs, and any contraindications to the use of busulfan or fludarabine, including known hypersensitivity to the active substances or to any of the excipients in their formulations. 15. Known hypersensitivity to protamine sulfate.