Genetic diagnosis history and osteoarticular phenotype of a non-transfusion secondary hemochromatosis

Table 1 Partial biochemical indicators in the patient with hemochromatosis

Item	Value	Abnormal condition	Normal range
Routine blood tests
White blood cells (× 109/L)	6.1	Normal	4.0-10.0
Hemoglobin (g/L)	92	Decrease	113-172
Hematocrit	0.32	Decrease	0.34-0.51
Mean corpuscular volume (fL)	65.2	Decrease	82.6-99.1
Mean corpuscular hemoglobin (pg)	19.0	Decrease	26.9-33.8
Mean corpuscular hemoglobin concentration (g/L)	291	Decrease	320-362
Red cell distribution width-SD	51.1	Normal	39.0-53.9
Red cell distribution width-CV (%)	23.3	Increase	11.9-14.5
Platelet count (× 109/L)	200	Normal	85-320
Reticulocytes (%)	4.2	Increase	0.5-2.0
Anemia indicators
Ferritin (μg/L)	1085.20	Increase	23.90-336.20
Serum total iron blinding capacity (μmol/L)	47.5	Decrease	50-77
Serum iron (μmol/L)	30.7	Increase	11-30
Serum unsaturated iron blinding capacity (μmol/L)	16.8	Decrease	25.0-52.0
Transferrin saturation (%)	64.6	Increase	20.0-55.0
Serum folic acid (ng/mL)	4.10	Decrease	> 5.21
Vitamin B12 (pg/mL)	398	Normal	180.0-914.0
Transferrin (g/L)	1.89	Decrease	2.00-3.60
Hemolysis test
Indirect anti-human globulin IgG test	Positive
Erythrocyte osmotic fragility test
Start hemolysis (mmol/L)	68.4	Decrease	71.8-78.6
Complete hemolysis (mmol/L)	41.0	Decrease	54.7-58.1
Biochemistry
Total bilirubin (μmol/L)	112.5	Increase	3.4-25.0
Direct bilirubin (μmol/L)	14.3	Increase	0.0-8.0
Indirect bilirubin (μmol/L)	98.2	Increase	0.0-20.0
ALT (IU/L)	26	Normal	5-64
AST (IU/L)	17	Normal	5-50
GGT (IU/L)	40	Normal	8-60
ALP (IU/L)	68	Normal	34-104
CHOL (mmol/L)	2.3	Decrease	3.0-5.7
LDLC (mmol/L)	1.0	Decrease	1.3-3.6
APROB (g/L)	0.39	Decrease	0.60-1.10
Fasting blood glucose	5.3	Normal	3.8-6.2
T3 (nmol/L)	1.32	Decrease	1.34-3.28
Routine urine tests
Bilirubin	2+		Negative
Protein	1+		Negative
Occult blood (RBC)	1+		Negative
Red blood cell count (n/μL)	31.5	Increase	0.0-9.9
Red blood cells (n/HP)	5.7	Increase	0.0-3.2
The number of undissolved RBCs (n/uL), ratio (%)	21.8 (69.1%)
C-reaction protein (mg/L)	36.70	Increase	0.00-5.00
Methemoglobin reduction rate (%)	31.72	Decrease	75.00-100.00

ALT: Alanine transaminase; AST: Aspartate transaminase; GGT: Glutamyltransferase; ALP: Alkaline phosphatase; CHOL: Total cholesterol; LDLC: Low-density lipoprotein cholesterol; APROB: Apolipoprotein B; T3: Triiodothyronine; RBC: Red blood cell.

Table 2 Possible mutation sites in the patient associated with hemochromatosis or psoriasis

Genes	RefSeq	Nucleic acid alternation	Amino acid alternation	Mut site	Zygotic	CytoBand	RS-ID	FRE in EAS	Mut- type	SIFT score	Polyphen2 score	MutationTaster score	Priority
PIEZO1	NM_001142864	c.C4748T	p.A1583V	Exon 35	Het	16q24.3	rs940442937	-	Mis	0.28	0.002	1	Medium
IFIH1	NM_022168	c.C2366T	p.T789I	Exon 12	Het	2q24.2	rs778200491	0.0013	Mis	0	1	1	High
KRT8	NM_002273	c.G1381A	p.V461M	Exon 8	Het	12q13.13	rs757168162	0.0031	Mis	0.097	0.197	1	High
POFUT1	NM_015352	c.A307G	p.I103V	Exon 3	Het	20q11.21	rs759090331	-	Mis	0.37	0.036	0.931	High
FLG	NM_002016	c.C7764A	p.S2588S	Exon 3	Het	1q21.3	rs561395256	0.0143	Syn	-	-	-	Medium
KRT2	NM_000423	c.303_304insGGC	p.F102delinsGF	Exon 1	Hom	12q13.13	rs56850150	0.5389	Nonfs ins	-	-	-	Medium
KRT2	NM_000423	c.300_301insGGCTTTGGAGGCGGC	p.S101delinsGFGGGS	Exon 1	Hom	12q13.13	rs57149265	0.5421	Nonfs ins	-	-	-	Medium
TGM5	NM_201631	c.A509G	p.Q170R	Exon4	Het	15q15.2	rs115121346	0.0025	Mis	0.858	0.343	0.83	High

Priority: The priority score of mutations is divided into four levels: High, likely high, medium, and low, the high level indicates that the site is located in gene’s exonic region, in the East Asian population (1000G, ExAC, gnomAD) frequencies are less than 0.01, resulting in changes in amino acids, and at least one protein prediction software predicts a detrimental result; the medium level indicates the site is located in the exonic or splicing region of the gene, and there is at least one result in which the frequency is less than 0.01 in the East Asian population (1000G, ExAC, gnomAD). RefSeq: NCBI Reference Sequence; Mut: Mutation; Het: Heterozygote; Hom: Homozygous; Cytoband: The chromosome segment in which the mutation is located; Mis: Missense mutation; Syn: Synonymous; Nonfs ins: Nonframeshift insertion; FRE: Frequency; EAS: Genome Aggregation Database East Asia; Polyphen2_HVAR_score: PolyPhen2 software is based on the HumanVar database to predict the impact of this variation on protein sequences; SNP: Single-nucleotide polymorphism; MAF: Minor allele frequency.