Renal, Ocular, and Neuromuscular Involvements in Patients with CLDN19 Mutations

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Figure 1.
Electrophysiological characteristics after prolonged exercise in two patients with CLDN19 mutations. The amplitude of CMAP was significantly decreased after exercise that lasted 5 minutes (according to Fournier et al. [13]). The amplitude of CMAP, recorded from the abductor digiti minimi muscle from 0 to 40 minutes after exercise, is expressed as a percentage of the pre-exercise value. In Patient F1.3, tests were performed while serum Mg²⁺ and K⁺ levels were normalized.
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Figure 2.
(A) Localization of CLDN19 mutations on the predicted model of claudin-19. The Val44 residue is localized within the claudin-specific W-GLW-C-C motif. (B) Genomic alignment around the Val44 (V) residue of CLDN19 of seven mammalian species (from the Ensembl database).

Table 1.

Phenotypic characteristics of three individuals with CLDN19 mutation

Characteristic	Patient			Normal Values
Characteristic	F1.3	F1.4	F2.3	Normal Values
Gender	Female	Female	Female
Mutation	p.Gly20Asp/p.Val44Met	p.Gly20Asp/p.Val44Met	p.Gly20Asp/p.Gly20Asp
Age at renal symptoms onset, years	10	0.9	16
Age at tests, years	16	13	16
Organ involvement
kidney	UTI, NL, NC	UTI, NL, NC	NC
eye	PM, Strab, nystagmus	PM	Strab, Myopia, Ir colobomata
nerve	Muscular-exercise intolerance	No	Muscular exercise intolerance
Blood tests
SCr, μmol/L	180	200	123
inulin clearance, ml/min per 1.73 m²	—	—	48.8
eGFR (sMDRD), ml/min per 1.73 m²	29	30	53.7
Mg²⁺, mmol/L	—	—	0.59	0.73 to 1.06
K⁺, mmol/L	3.5	3.3	3.7	3.5 to 5
HCO₃⁻, mmol/L	23	17	28	21 to 30
Ca²⁺, mmol/L	2.1	1.84	2.35	2.2 to 2.6
PO₄³⁻, mmol/L	1.32	1.74	0.82	0.8 to 1.5
25(OH)vitamin D₃, ng/ml	—	—	13.3	9 to 45
1,25(OH)₂ vitamin D₃, pg/ml	—	—	69	18 to 60
IPTH, pg/ml	—	150	155	15 to 85
alkaline phosphatase, IU/L	207	656	208	100 to 280
Urinary tests
FeMg²⁺, %^{^a}	—	—	9.9	<2%
Ca²⁺/Cr ratio, mg/mg	0.9	1.2	0.9	<0.4
TmPO₄³⁻, %	—	—	83.5	>85
citrate, mg/24 h	101	285	362.4	400 to 900
oxalate, μmol/24 h	186	163	232.8	200 to 450
pH (nocturnal)	—	—	6.36
proteinuria, mg/24 h	—	—	510	<300
hematuria, (0 to 3+)	0	0	0
drug intake	Calcium pyridoxine	Calcium pyridoxine	No
Renal outcome
eGFR (sMDRD)	ESRD (at age 22)	ESRD (at age 16)	51 (at age 17)

UTI, urinary-tract infection; NL, nephrolithiasis; NC, nephrocalcinosis; SCr, serum creatinine; PM, pigmentary maculopathy; Strab, strabismus; Ir, Iris; sMDRD, standard Modifications of Diet in Renal Disease equation; TmPO4³⁻, maximum rate of renal tubular reabsorption of phosphate.
↵a FeMg²⁺ was calculated as follows: urinary/plasma [Mg²⁺]/urinary/plasma [creatinine].