Hb Vanvitelli: A new unstable α-globin chain variant causes undiagnosed chronic haemolytic anaemia when co-inherited with deletion - α3.7.

Abstract

Hb variants are structurally abnormal haemoglobins which can originate a wide range of phenotypes from clinically silent conditions to very severe disorders. In many cases, diagnosis is very difficult due to the instability of Hb mutants or the occurrence of misleading symptoms, such as cyanosis or hypoxia. Here we report the case of a young female with undiagnosed chronic haemolytic anaemia and low oxygen saturation in the absence of respiratory distress. High performance liquid chromatography showed the occurrence of an abnormal peak in the HbA2 region, which disappeared few days after blood sampling. Genetic analysis of both α genes revealed the -α3.7 deletion in heterozygous state and a novel mutation c.130 T > C leading to the substitution of Phenylalanine at codon 43 with Leucine in the α1 gene. This substitution originated a new Hb variant, named Hb Vanvitelli, with a molecular mass of 15,092.2 ± 0.4 Da. Biochemical and laboratory tests described a hyper unstable Hb variant with altered oxygen affinity that was clinically significant only when co-inherited with genetic defects affecting the α2 locus. This case highlights the genetic complexity and diagnostic pitfalls of Hb variants, defined "experiments of nature" which can generate severe clinical conditions.

• Authors: Maddalena Casale, Flora Cozzolino, Saverio Scianguetta, Piero Pucci, Vittoria Monaco, Gianmaria Sanchez, Claudia Santoro, Roberta Rubino, Monica Cannata, Silverio Perrotta
• Journal: Clinical biochemistry (Clin Biochem) Vol. 74 Pg. 80-85 (Dec 2019) ISSN: 1873-2933 [Electronic] United States
• PMID: 31493379 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Chemical References

• Codon
• Hemoglobins, Abnormal
• alpha-Globins
• Oxygen

Topics

• Adolescent
• Amino Acid Sequence (genetics)
• Amino Acid Substitution (genetics)
• Anemia, Hemolytic (blood, diagnosis, genetics)
• Chromatography, Liquid
• Chronic Disease
• Codon (genetics)
• Female
• Genetic Testing
• Hemoglobins, Abnormal (genetics)
• Heterozygote
• Humans
• Italy
• Mass Spectrometry
• Oximetry
• Oxygen (blood)
• Pedigree
• Phenotype
• Sequence Deletion
• alpha-Globins (genetics)