Iron metabolism disorders - NOT common HFE mutations

Gene: FECH

I don't know

Comment on list classification: As the iron deficiency resulting from FECH mutations is mild (low to low-normal serum iron), this gene does not fit into the scope of this panel, and it should remain Amber.

Created: 2 Jan 2026, 3:58 p.m. | Last Modified: 2 Jan 2026, 3:58 p.m.

Panel Version: 3.3

FECH product, ferrochelatase, is an enzyme in the heme biosynthesis pathway that catalyses insertion of an iron atom into protoporphyrin IX. According to Barman-Aksoezen et al., 2017 (PMID: 28185024) Erythropoietic protoporphyria (EPP) patients 'frequently exhibit low serum iron and a microcytic hypochromic anemia'. However, as reviewed by Sharon Whatley, the iron deficiency is often mild (low to low-normal serum iron).

PMID: 21659066 Morais et al., 2011
Portuguese male proband with compound het mutations c.1052delA, p.Glu351Glyfs*6 and IVS3-48T>C in FECH - diagnosed with EPP, presented with acute episodes of photosensitivity, microcytic anemia and mild hepatic dysfunction.

PMID: 20412370 Wahlin et al., 2011
Swedish cohort of 51 EPP patients - 44% had low ferritin levels.

PMID: 28614581 Balwani et al., 2017
US report of 226 patients, 37.4% of EPP patients were anemic.

FECH is associated with Protoporphyria, erythropoietic,1 OMIM:177000 (OMIM accessed 26th Nov 2025).

Created: 26 Nov 2025, 5:50 p.m. | Last Modified: 28 Nov 2025, 2:51 p.m.

Panel Version: 3.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Protoporphyria, erythropoietic,1 OMIM:177000; protoporphyria, erythropoietic, 1 MONDO:0008319

Publications

• 20412370
• 21659066
• 28185024
• 28614581

Red List (low evidence)

Erythropoietic protoporphyria (EPP) is not primarily a disorder of iron metabolism although it can be associated with it. It is a disorder of the haem biosynthetic pathway and is characterized by the accumulation of metal-free protoporphyrin in erythrocytes, plasma, and the biliary system. The iron deficiency is mild and not observed in all patients and typically has little clinical impact.

PMID: 28185024 Barman-Aksoezen shows that EPP patients have chronic iron deficiency possibly due to a block in iron absorption at the intestinal wall by a hepcidin-independent mechanism or an intestinal iron loss.

Created: 28 Aug 2025, 3:57 p.m. | Last Modified: 28 Aug 2025, 3:57 p.m.

Panel Version: 3.1

Publications

• 28185024

I don't know

Green List (high evidence)

Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group.

Created: 18 Feb 2019, 11:45 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
177000 PROTOPORPHYRIA, ERYTHROPOIETIC, 1; EPP1

Green List (high evidence)

Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.

Created: 13 Feb 2019, 12:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
177000 PROTOPORPHYRIA, ERYTHROPOIETIC, 1; EPP1

I don't know

Comment on list classification: Downgraded from Green to Amber. As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene to Amber.

Created: 22 Jul 2019, 3:14 p.m. | Last Modified: 22 Jul 2019, 3:14 p.m.

Panel Version: 0.48

Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Amber

Created: 28 May 2019, 2:08 p.m.

Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: FECH; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 177000.PROTOPORPHYRIA, ERYTHROPOIETIC, 1; EPP1; PMID(s): none submitted

Created: 18 Feb 2019, 11:49 a.m.

Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: FECH; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 177000 PROTOPORPHYRIA, ERYTHROPOIETIC, 1; EPP1; PMID(s): none submitted

Created: 13 Feb 2019, 12:39 p.m.

Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: FECH; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 177000 PROTOPORPHYRIA, ERYTHROPOIETIC, 1; EPP1; PMID(s): 20857522; 26387792; 28614581

Created: 5 Feb 2019, 5:51 p.m.

Green List (high evidence)

Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.

Created: 5 Feb 2019, 5:50 p.m.