7501 T > A mitochondrial DNA variant in a patient with glomerulosclerosis

Figures & data

Table 1. The findings of laboratory tests performed on admission.

Blood cell count		Blood chemistry		Immunology		Hormones
WBC	8000/mL	TP	8.1 g/dL	ASO	56 U/mL	TSH	1.45 µIU/ml
RBC	5.10 × 10^6/mL	Alb	4.3 g/dL	C3	133 mg/dL	fT3	2.97 pg/ml
Hb	14.9 g/dL	AST	24 IU/L	C4	22.3 mg/dL	fT4	1.45 ng/dl
Hct	45.2%	ALT	18 IU/L	IgG	1891 mg/dL
MCV	89 fl	LDH	225 IU/L	IgA	183 mg/dL	Urinalysis
MCHC	33.0%	ALP	150 IU/L	IgM	248 mg/dL	Gravity	1.010
Platelet	25.1 × 10^4/mL	Tbil	0.9 mg/dL	RA test	(–)	pH	5.5
		BUN	15.6 mg/dL	ANA	(–)	RBC	0–1 /HPF
Coagulation		Cr	0.76 mg/dL	M protein	(–)	WBC	0–1 /HPF
APTT	34.0 sec	UA	9.4 mg/dL	HBs antigen	(–)	Ccr (24 hr)	63.3 mL/min
PT(%)	86%	Tcho	214 mg/dL	HCV antibody	(–)	Protein	0.68 g/day
INR	1.1 INR	CRP	0.22 mg/dL	MPO-ANCA	67.5 EU	NAG	4.3 U/L
		FBS	126 mg/dL	PR3-ANCA	<10 EU	β2-MG	<20 mg/L
		HbA1c	7.5%	TSHrAb	3.8 IU/l	BJP	(–)
		digoxin	1.4 ng/ml

Aberrant values are underlined.

WBC, white blood cells; RBC, red blood cells; Hb, hemoglobin; Hct, hematocrit; MCV, mean corpuscular volume; MCHC, mean corpuscular hemoglobin; APTT, activated partial thromboplastin time; PT, prothrombin time; INR, international normalized ratio; TP, total protein; Alb, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; Tbil, total bilirubin; BUN, blood urea nitrogen; Cr, creatinine; UA, uric acid; Tcho, total cholesterol; CRP, C-reactive protein; FBS, fasting blood sugar; HbA1c, hemoglobin A1c (NGSP); ASO, antistreptolysin-O; C3, complement 3; IgG, immunoglobulin G; RA, rheumatoid arthritis; ANA, antinuclear antibody; M protein, monoclonal protein; HBs, hepatitis B surface; HCV, hepatitis C virus; MPO-ANCA, myeloperoxidase-anti-neutrophil cytoplasmic antibody; PR3, proteinase 3; TSHrAb, thyroid-stimulating hormone receptor antibodies; fT3, free triiodothyronine; fT4, free thyroxin; Ccr, creatinine clearance; NAG, N-acetylglutamate; MG, microglobulin; BJP, Bence Jones protein. To convert Hb, TP and Alb in g/dL to g/L, multiply by 10; Tbil in mg/dL to µmol/L, multiply by 17.1; BUN in mg/dL to mmol/L, multiply by 0.357; Cr in mg/dL to µmol/L, multiply by 88.4; UA in mg/dL to µmol/L, multiply by 59.48; Tcho in mg/dL to mmol/L, multiply by 0.02586; C3, C4, IgG, IgA and IgM in mg/dL to g/L, multiply by 0.01; and Ccr in mL/min to mL/sec, multiply by 0.01667.

Figure 1. The light microscopic findings. (A) While globally sclerosed glomeruli and collapsed glomeruli were observed, the other glomeruli showed an almost normal appearance (Masson trichrome stain, original magnification ×40). (B) This glomerulus looks normal. However, the vascular smooth muscle cells are disorganized and enlarged (PAM-HE stain, original magnification ×200). (C) This glomerulus also looks normal, while the myocytes of the afferent arteriole are enlarged and their endothelium has slight hyalinosis (PAM-HE stain, original magnification ×200). (D) Granular swollen epithelial cells are indicated by arrows (Masson trichrome stain, original magnification ×400).

Figure 2. The electron microscopic findings. (A) The foot processes of podocytes are effaced (asterisks). (B) The granular swollen epithelial cells have increased numbers of mitochondria, a portion of which are enlarged, and some of which have cristae that have lost their normal structure.

Figure 3. The results of the direct sequencing of mtDNA. A homoplasmic 7501 T > A variant in the tRNASer(UCN) was detected in the patient’s blood sample.

Figure 4. The B-mode echocardiogram. (A) The cardiac echogram on admission showed hypokinetic wall motion and anteroseptal hypokinesis. The ejection fraction determined by the modified Simpson’s method was 45.9%. (B) One year after the prescription of a β-blocker, the cardiac echogram showed normal wall motion of the anteroseptum. The ejection fraction determined by a modified Simpson’s method was 60.7%.

Figure 5. The changes of the systolic blood pressure (SBP), the degree of proteinuria and the estimated glomerular filtration rate (eGFR). The vertical line shows the time when the β-blocker was prescribed.