ESPE Abstracts

Objective: The systemic form pseudohypoaldosteronism type 1 (PHA1) is an autosomal recessive disorder characterized with defective sodium transport in many organ systems including kidney, lungs, colon, sweat glands and salivary glands. Homozygous or compound heterozygous loss-of-function mutations in the genes encoding amiloride sensitive epithelial sodium channel (ENaC) account for genetic causes of systemic PHA1.

Case 1: Male patient presented with vomiting, poor feeding, discomfort and skin rash. He had normal male external genitalia, no hyperpigmentation and normal blood pressure. In laboratory investigations severe hyponatremia (NA:106 Eq/l), hyperkalemia (K:11.8 mEq/l), metabolic acidosis (pH:7.16, HCO3:9 mEq/l), elevated plasma renin (98.2 ng/ml; N:.4–37), elevated aldosterone (3173 pg/ml; N: 86–1340) and positive sweat test (147 mEq/l) suggested the diagnosis of systemic PHA1. In the molecular genetics analysis a novel compound heterozygous [c.87 C >A(p.Tyr29*)/IVS9+1G >A (c.1346+1G >A)] mutation was detected in SCNN1B gene.

Case 2: A female admitted with vomiting, poor feeding, and weight loos. She was appeared unwell, agitated and restless. She had a normal female external genitalia with no hyperpigmentation. In laboratory investigations severe hyponatremia (Na: 117 mEq/l), hyperkalemia (K:9.8 mEq/l), metabolic acidosis (pH:7.24, HCO3:12.1 mEq/l), elevated plasma renin (96.9 ng/ml; N:. 4–37), elevated aldosterone(3032 pg/ml; N: 86–1340) and positive sweat test (112 mEq/l) suggested the diagnosis of systemic PHA1. In the molecular genetics analysis a homozygous [p.T663A(c.1987A>G] mutation was detected in SCNN1A gene.

Case 3: A female neonates admitted to our clinic with the complaints of weakness and poor feeding. At presentation she was unwell, had 3/6 systolic murmur, decreased skin turgor-tonus and dyspnea. She had normal female external genitalia with no skin pigmentation. In laboratory investigations severe hyponatremia (Na:109 mEq/l), hyperkalemia (K:10.9 mEq/l), metabolic acidosis (pH:7.11, HCO3: 8.2 mEq/l), elevated plasma renin (104.2 ng/ml; N:. 4–37), elevated aldosterone (5882 pg/ml; N: 86–1340) and positive sweat test (134 mEq/l) suggested the diagnosis systemic PHA1. In the molecular genetics analysis a homozygous p.A200Gfs*6(c.598dupG) mutation was detected in SCNN1A gene.

Conclusion: In patients presenting with hyponatremia, hyperkalemia and metabolic acidosis, particularly with absence of disorders of sexual differentiation and hyperpigmentation systemic form PHA1 should be considered in the differential diagnosis. Present cases with 3 novel mutations would add novel insights into our understanding the pheotype-genotype relationship of systemic PHA1 and expand the mutation database.