Pseudohypoaldosteronism type 1b in fraternal twins of a Chinese family: report of two cases and literature review

Gao, Zhen; Sun, Jingjing; Cai, Cheng; Gong, Xiaohui; Ma, Li

doi:10.20945/2359-3997000000620

Zhen Gao

interpreted the data and wrote the manuscript

Department of Neonatology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

http://orcid.org/0000-0002-2676-8742

Jingjing Sun

collected clinical information and provided genetic counseling

provided patient samples and determined the phenotype based on the clinical presentation

Department of Neonatology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, China

http://orcid.org/0000-0002-7077-4058

Cheng Cai

collected clinical information and provided genetic counseling

Department of Neonatology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, China

http://orcid.org/0000-0002-9320-0495

Xiaohui Gong

designed the study and revised the manuscript

Department of Neonatology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, China

http://orcid.org/0000-0001-7956-8608

Li Ma Correspondence to: Li Ma mali2340@shchildren.com.cn

provided patient samples and determined the phenotype based on the clinical presentation

designed the study and revised the manuscript

Department of Neonatology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, China

http://orcid.org/0000-0003-3212-0704

Correspondence to: Li Ma mali2340@shchildren.com.cn

Disclosure: no potential conflict of interest relevant to this article was reported.

Patients	Case 1	Case 2	Reference range
Sex	Female	Male
Birth	Term	Term
Birth weight (g)	2.800	3.100
Consanguinity of family history	No	No
Day of onset	8	9
Primary symptoms	Poor response, refusing milk Heterozygous intronic missense mutations in SCNN1A c.1439+1G>C and c.875+1G>A	Poor response, refusing milk Heterozygous intronic missense mutations in SCNN1A c.1439+1G>C and c.875+1G>A
Serum HCO3 (mmol/L)	12.9	11.3	18-23
Serum Creatine (μmol/L)	67	87	27-66
Serum Sodium (mmol/L)	117	127	136-145
Serum Potassium (mmol/L)	10.4	10.1	3.5-5.2
PH	7.09	7.06	7.33-7.49
BE (mmol/L)	-15.8	-26.7	-3-3
Lactose (mmol/L)	11.4	9.7	0.5-2.2
Aldosterone (ng/L)	>2000	1337.18	59.5-173.9
Plasma renin activity (μg/dL/h)	N/A	9.47	0-15
ACTH (pmol/L) 8am	3.75	8.5	1.59-14
Cortisol (nmol/L)	671.86	348.03	185.00-624.00
Renal ultrasound	Normal	Normal
Testosterone (nmol/L)	3.87	4.82
17-OHP(ng/mL)	7.8	9.27	0-11
Management		When discharged from hospital, he was intake with 10% NaCl at 10 mEq/kg/d and ionexchange resins at 1 g/kg/d
Complication	Died on day 2 of admitted in hospital due to cardiac arrest	Died at 5 months after birth due to cardiac arrest

	Variant	AA change	Classification	Exon/intron
1	c.-55+2T>C	p.?	VUS	1^st Intron
2	c.107C>T	p.(Ala36Val)	likely benign	2^nd Exon
3	c.166C>T	p.(Arg56*)	pathogenic	2^nd Exon
4	c.189C>A	p.(Cys63*)	pathogenic	2^nd Exon
5	c.203_204del	p.(Ile68Thrfs*76)	pathogenic	2^nd Exon
6	c.206A>G	p.(His69Arg)	pathogenic	2^nd Exon
7	c.217C>T	p.(Arg73Cys)	pathogenic	2^nd Exon
8	c.301C>A	p.(Gln101Lys)	pathogenic	2^nd Exon
9	c.416G>A	p.(Arg139Lys)	pathogenic	2^nd Exon
10	c.505_506del	p.(Thr169Serfs*36)	pathogenic	3^rd Exon
11	c.540G>T	p.(Leu180=)	benign	3^rd Exon
12	c.587dup	p.(Pro197Alafs*9)	pathogenic	3^rd Exon
13	c.598dup	p.(Ala200Glyfs*6)	pathogenic	3^rd Exon
14	c.684+2T>A	p.?	pathogenic	3^rd Intron
15	c.727T>C	p.(Ser243Pro)	pathogenic	4^th Exon
16	c.729del	p.(Val245Trpfs*4)	pathogenic	4^th Exon
17	c.742del	p.(Val248*)	pathogenic	4^th Exon
18	c.814dup	p.(Glu272Glyfs*39)	pathogenic	4^th Exon
19	c.875+1C>A	p.?	Likely pathogenic	4^th Intron
20	c.875+2dup	p.?	pathogenic	4^th Intron
21	c.979G>T	p.(Gly327Cys)	pathogenic	5^th Exon
22	c.997C>T	p.(Arg333Cys)	VUS	5^th Exon
23	c.1000G>A	p.(Ala334Thr)	benign	6^th Exon
24	c.1305del	p.(Tyr436Ilefs*46)	pathogenic	8^th Exon
25	c.1311del	p.(Arg438Glyfs*44)	pathogenic	8^th Exon
26	c.1339dup	p.(Tyr447Leufs*13)	pathogenic	8^th Exon
27	c.1344_1347dup	p.(His450Lysfs*11)	pathogenic	8^th Exom
28	c.1356del	p.(Trp453Glyfs*29)	pathogenic	8^th Exon
29	c.1358G>T	p.(Trp453Leu)	VUS	8^th Exon
30	c.1360+1G>T	p.?	pathogenic	8^th Intron
31	c.1361-2A>G	p.?	Pathogenic	8^th Intron
32	c.1435T>C	p.(Cys479Arg)	VUS	9^th Exon
33	c.1439+1G>C	p.?	Pathogenic	9^th Intron
34	c.1449del	p.(Tyr484Thrfs*13)	pathogenic	10^th Exon
35	c.1474C>T	p.(Arg492*)	pathogenic	10^th Exon
36	c.1477T>C	p.(Trp493Arg)	benign	10^th Exon
37	c.1522C>T	p.(Arg508*)	pathogenic	11^th Exon
38	c.1582_1584del	p.(Phe528del)	pathogenic	12^th Exon
39	c.1678G>A	p.(Gly560Ser)	pathogenic	13^th Exon
40	c.1684T>C	p.(Ser562Pro)	pathogenic	13^th Exon
41	c.1685C>T	p.(Ser562Leu)	pathogenic	13^th Exon
42	c.1772G>A	p.(Arg591Gln)	VUS	13^th Exon
43	c.1978A>G	p.(Ser660Gly)	likely benign	13^th Exon
44	c.1987A>G	p.(Thr663Ala)	benign	13^th Exon
45	c.2004dup	p.(Pro669AlafsTer62)	VUS	13^th Exon

[1] Correspondence to: Li Ma mali2340@shchildren.com.cn

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Pseudohypoaldosteronism type 1b in fraternal twins of a Chinese family: report of two cases and literature review

SUMMARY