PMID- 32487371
OWN - NLM
STAT- MEDLINE
DCOM- 20210215
LR  - 20210215
IS  - 1879-0828 (Electronic)
IS  - 0953-6205 (Linking)
VI  - 79
DP  - 2020 Sep
TI  - Hyperhomocysteinemia in patients with acute porphyrias: A potentially dangerous 
      metabolic crossroad?
PG  - 101-107
LID - S0953-6205(20)30115-1 [pii]
LID - 10.1016/j.ejim.2020.04.002 [doi]
AB  - BACKGROUND: Acute porphyrias (AP) are characterized by heme deficiency and 
      induction of hepatic 5-aminolevulinate synthase (ALAS1). Hyperhomocysteinemia 
      (HHcy) is associated with endothelial damage, neurotoxicity and increased risk 
      for vascular diseases. Interestingly, both heme biosynthesis and sulphur amino 
      acid metabolism require vitamin B6, (Pyridoxal-phosphate, PLP) an important 
      cofactor of ALAS1 and of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase 
      (CGL) enzymes that catabolize homocysteine (Hcy). Moreover, heme itself is an 
      important cofactor for CBS. AIM: to assess plasma Hcy status and HHcy main 
      determinants in patients with AP. MATERIALS AND METHODS: A total of 46 patients 
      with AP (31 with Acute Intermittent Porphyria,15 with Variegate Porphyria) were 
      assessed for clinical status (symptomatic vs. asymptomatic), serum Hcy, Cysteine 
      (Cys), Vit.B6, Vit.B12, red blood cell folates and urinary delta-aminolevulinic 
      acid (ALA) and porphobilinogen(PBG) levels (mean of six measurements). RESULTS: 
      Symptomatic AP patients had significantly higher urinary ALA and PBG levels, 
      plasma Hcy, HHcy prevalence and Hcy/Cys ratio when compared to asymptomatic 
      carriers of AP. Even though no significant correlation was observed between 
      ALA/PBG urinary levels and serum Hcy levels, patients with higher levels of ALA 
      and PBG had significantly higher levels of Hcy, a higher prevalence of 
      moderate-to severe HHcy and serum PLP levels below the 25(th) percentile of a 
      reference assessment with 300 healthy Italian subjects(<45nmol/L). CONCLUSIONS: 
      Most patients with symptomatic AP present HHcy resulting from alterations in 
      sulphur amino acid metabolism. HHcy may represent an indirect marker of ALAS1 
      induction and its prevalence may be suggestive of a role of HHcy in the 
      pathogenesis and/or comorbidities of AP.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Ventura, Paolo
AU  - Ventura P
AD  - Unit of Internal Medicine, Department of Medical and Surgical Science for 
      Children and Adults, University of Modena and Reggio Emilia, Italy. Electronic 
      address: paoloven@unimore.it.
FAU - Corradini, Elena
AU  - Corradini E
AD  - Unit of Internal Medicine, Department of Medical and Surgical Science for 
      Children and Adults, University of Modena and Reggio Emilia, Italy.
FAU - Di Pierro, Elena
AU  - Di Pierro E
AD  - Department of Internal Medicine, IRCCS Ca Granda Foundation, University of Milan, 
      Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Marchini, Stefano
AU  - Marchini S
AD  - Unit of Internal Medicine, Department of Medical and Surgical Science for 
      Children and Adults, University of Modena and Reggio Emilia, Italy.
FAU - Marcacci, Matteo
AU  - Marcacci M
AD  - Unit of Internal Medicine, Department of Medical and Surgical Science for 
      Children and Adults, University of Modena and Reggio Emilia, Italy.
FAU - Cuoghi, Chiara
AU  - Cuoghi C
AD  - Unit of Internal Medicine, Department of Medical and Surgical Science for 
      Children and Adults, University of Modena and Reggio Emilia, Italy.
FAU - Buzzetti, Elena
AU  - Buzzetti E
AD  - Unit of Internal Medicine, Department of Medical and Surgical Science for 
      Children and Adults, University of Modena and Reggio Emilia, Italy.
FAU - Pietrangelo, Antonello
AU  - Pietrangelo A
AD  - Unit of Internal Medicine, Department of Medical and Surgical Science for 
      Children and Adults, University of Modena and Reggio Emilia, Italy.
LA  - eng
PT  - Journal Article
DEP - 20200531
PL  - Netherlands
TA  - Eur J Intern Med
JT  - European journal of internal medicine
JID - 9003220
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - P6YC3EG204 (Vitamin B 12)
SB  - IM
MH  - Cystathionine beta-Synthase
MH  - Homocysteine
MH  - Humans
MH  - *Hyperhomocysteinemia/epidemiology
MH  - *Porphyria, Acute Intermittent/complications/epidemiology
MH  - Vitamin B 12
OTO - NOTNLM
OT  - Acute Porphyrias
OT  - Ala-Synthase1
OT  - Homocysteine
OT  - Hyperhomocysteinemia
OT  - Vitamin B6
EDAT- 2020/06/04 06:00
MHDA- 2021/02/16 06:00
CRDT- 2020/06/04 06:00
PHST- 2019/09/03 00:00 [received]
PHST- 2020/03/19 00:00 [revised]
PHST- 2020/04/01 00:00 [accepted]
PHST- 2020/06/04 06:00 [pubmed]
PHST- 2021/02/16 06:00 [medline]
PHST- 2020/06/04 06:00 [entrez]
AID - S0953-6205(20)30115-1 [pii]
AID - 10.1016/j.ejim.2020.04.002 [doi]
PST - ppublish
SO  - Eur J Intern Med. 2020 Sep;79:101-107. doi: 10.1016/j.ejim.2020.04.002. Epub 2020 
      May 31.