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.

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

Cozzolino F.
Co-primo
;
SCIANGUETTA, CONCETTA;Pucci P.;
2019

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.
File in questo prodotto:
File Dimensione Formato  
Clin Biochem_2019.pdf

accesso aperto

Descrizione: Articolo principale
Licenza: Dominio pubblico
Dimensione 2.66 MB
Formato Adobe PDF
2.66 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/759827
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 1
social impact