Mutation analysis and audiologic assessment in six Chinese children with primary distal renal tubular acidosis

Figures & data

Table 1. Clinical characteristic at diagnosis of six children with distal renal tubular acidosis.

Patient	I-1	II-1	III-1	III-2	IV-1	IV-2
Gender	F	M	F	M	F	M
Current age (years)	2	3	11	8	13	11
Age at diagnosis (weeks)	7	13	22	4	17	9
Manifestation	Pneumonia, vomiting	Vomiting, dehydration	Growth retardation	Family study	Dehydration	Family study
Height (cm)^a	54.0 (56.0)	59.0 (61.5)	58.0 (64.5)	52.5 (54.5)	62 (62.2)	56.5 (59.0)
Weight (kg)^a	4.0 (4.7)	5.4 (6.3)	5.7 (7.1)	4.2 (4.5)	5.8 (6.2)	4.8 (5.5)
Blood pH	7.32	7.31	7.26	7.20	7.23	7.25
SHCO3	13.9	14.2	12.0	9.9	11.0	10.0
SK	3.3	3.1	2.8	3.1	4.2	2.6
Ionized SCa (mmol/L, 1.12–1.23)	1.42	1.22	1.20	1.23	1.62	1.19
SCr (μmol/L)	26.5	26.7	23.5	31.1	27.6	28.1
GFR (mL/min/1.73 m^2)^b	74	80	89.5	63	81	73
UpH	7.5	8.0	8.5	7.5	8.0	8.5
UCa/Cr (mg/mg)^c	0.53	0.68	0.71	0.93	0.77	0.89
FEHCO3 (%)	4.0	3.5	NA	4.8	3.7	2.8
Nephrocalcinosis	2	2	3	1	2	1

Notes: S, serum; U, urinary; FEHCO₃, fractional excretion of bicarbonate; NA, not available.

^aThe 50th percentile of Chinese children normal reference values for height and weight of different ages and genders at diagnosis.

^bGFR (calculated by Bedside Schwartz equation) = (0.41 × Height in cm)/Creatinine in mg/dl.

^cThe 95th percentile of normal reference values for UCa/Cr was 0.86 mg/mg for infants less than 7 months.

Table 2. Hearing status and inner ear radiologic characteristics of these children with distal renal tubular acidosis.

Patient	Age at confirmation of hearing loss (months)	SNHL	EVA	Therapy	Screening device	Type of UNHS	Results of UNHS^a
I-1	9	Bilateral profound	Positive (MRI at 12 months)	Cochlear implants	GSI AUDIO screener	DPOAE	Bilateral pass
II-1	7	Bilateral profound	Positive (CT at 12 months)	Cochlear implants	GSI AUDIO screener	DPOAE	Unilateral pass
III-1		No	Negative (MRI at 11 years)		NATUS ALGO 3i	AABR	Bilateral pass
III-2	37	Bilateral moderate	Positive (MRI & CT at 3 years)	Hearing aids	NATUS ALGO 3i	AABR	Bilateral pass
IV-1		No	Negative (MRI at 7 years)		ILO v6	TEOAE	Bilateral pass
IV-2	60	Bilateral moderate	Negative (MRI at 5 years)	Hearing aids	ILO v6	TEOAE	Bilateral pass

Notes: SNHL, sensorineural hearing loss; EVA, enlarged vestibular aqueduct; UNHS, universal newborn hearing screening; MRI, magnetic resonance imaging; CT, computed tomography; DPOAE, distortion product otoacoustic emission; AABR, automated auditory brainstem response; TEOAE, transient evoked otoacoustic emissions.

^aSetting threshold at 35 dB.

Figure 1. Novel mutations identified in ATP6V1B1 and ATP6V0A4 of patients with distal renal tubular acidosis. The mutant nucleotides are marked with asterisks.

Table 3. Detected mutations in ATP6V1B1 and ATP6V0A4 of the six children with distal renal tubular acidosis.

Patient	ATP6V1B1^a gene mutation	ATP6V0A4^b gene mutation
I-1	c.[1155dupC];[1356delT] (p.[Ile386Hisfs*56];[Phe452Leufs*35])
II-1	c.[786-1G > C];[786-1G > C] (r.[spl?];[spl?]])
III-1, III-2		c.[C580 > T];[C580 > T] (p.[Arg194*];[Arg194*])
IV-1, IV-2		c.[2258-1G > C];[2137delG] ([r.spl?];[p.Glu713fs*53])

Notes: ^aNucleotides numbered according to the sequence in GenBank NM_001692.

^bNucleotides numbered according to the sequence in GenBank NM_020632.

Figure 2. High-resolution computed tomography (CT) and magnetic resonance imaging (MRI) of the temporal bones in patient III-2. Bilateral enlargement of the vestibular aqueduct and endolymphatic sac (arrows) is evident.

Figure 3. Audiograms of patients III-2 and IV-2. (A) Audiogram of patient III-2 at age of 5 years. (B) Audiogram of patient III-2 at age of 8 years. (C) Audiogram of patient IV-2 at age 5 years. Bilateral air–bone gaps are recognized, especially at lower frequencies in patient III-2. Circle or × indicate unmasked examination of air conduction for the right or left ear, triangle or square indicate masked examination of air conduction for right or left ear, < or > indicate unmasked bone conduction for right or left ear, [ or ] indicate masked bone conduction for right or left ear.