Thirteen‐month‐old girl with hyporegenerative macrocytic anemia due to Brown–Vialetto–Van Laere syndrome 2

Abstract: A 13-month-old girl was admitted to the clinic with a newly acquired horizontal nystagmus that had been present for 4 weeks. Additionally, she had not made any further motor developmental steps in the last 4 months and could neither crawl nor sit freely. MRI of the brain and EEG showed no pathological findings. Eye and ear examinations revealed optic atrophy and impaired hearing. Additionally, initial laboratory findings showed hyporegenerative macrocytic anemia with hemoglobin 6.7 g/dL, mean corpuscular volume 101 fL, and reticulocyte count 20 × 103/μL (Normal 44–111). A thorough workup of blood detected normal serum levels of vitamin B12, holotranscobalamin, methylmalonic acid, folic acid, and zinc. As hemoglobin steadily decreased, transfusions had to be performed. An aspiration of bone marrow proved game-changing, as it revealed severe hypoplasia of erythropoiesis and a striking vacuolization of myelocytes, proerythroblasts, and micromegakaryocytes (Image 1A). We suspected Pearson syndrome, but could not demonstrate a deletion of mitochondrial DNA. By contrast, whole exome sequencing identified two compound heterozygous variants in the SLC52A2 gene. Mutations in the SLC52A2 gene are a known cause of Brown–Vialetto–Van Laere syndrome 2 (BVVL 2), a rare disorder of the riboflavin transporter, which is necessary for cellular uptake of this vitamin.1 Defective riboflavin transport results in impaired cofactor and cellular energy metabolism. Symptoms of BVVL 2 include optic atrophy, hearing impairment, bulbar palsy, muscle weakness, respiratory compromise, and dysfunction of erythropoiesis.1-3 Unlike Pearson syndrome, a disease that is always fatal and still lacking curative options, BVVL 2 can be treated successfully with supra-physiological doses of riboflavin.4 The girl revealed rapid significant neurological improvement and complete disappearance of anemia after 6 weeks of high-dose oral riboflavin substitution with 80 mg/kg per day. Remission was clearly evident in the control bone marrow aspiration (Image 1B). We suggest Brown–Vialetto–Van Laere syndrome type 2 as an important differential diagnosis in hyporegenerative macrocytic anemia. Rapid diagnosis and initiation of therapy are crucial for the remedy of hematological and neurological impairment and full reconstitution

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: American journal of hematology. - 97, 11 (2022) , 1495-1496, ISSN: 1096-8652

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2022
• Urheber: Naami, Nibras ; Borkhardt, Arndt ; Yoshimi-Nöllke, Ayami ; Grinstein, Lev ; Escherich, Gabriele

Weitere Informationen

• DOI: 10.1002/ajh.26573
• URN: urn:nbn:de:bsz:25-freidok-2268519
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:25 MESZ