The reference OMIM entry for this protein is 177735

Pseudohypoaldosteronism, type i, autosomal dominant; pha1a
Pha i, autosomal dominant

A number sign (#) is used with this entry because autosomal dominant pseudohypoaldosteronism type I (PHA1A) is caused by heterozygous mutation in the mineralocorticoid receptor gene (MCR, NR3C2; 600983).

DESCRIPTION

Autosomal dominant pseudohypoaldosteronism type I is characterized by salt wasting resulting from renal unresponsiveness to mineralocorticoids. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment. Some adult patients with the disorder may have elevated aldosterone levels, but no history of clinical disease. This observation suggests that only those infants whose salt homeostasis is stressed by intercurrent illness and volume depletion develop clinically recognized PHA I (summary by Geller et al., 1998). Autosomal recessive PHA (PHA1B; 264350), caused by mutation in any one of 3 genes encoding the epithelial sodium channel (ENaC), is a similar but more severe systemic disorder with persistence into adulthood.

CLINICAL FEATURES

Hanukoglu (1991) reported a family with autosomal dominant inheritance of PHA (Hanukoglu et al., 1978). The proband presented with renal salt wasting in infancy, associated with vomiting, failure to thrive, and short stature. Laboratory studies showed hyponatremia and hyperkalemia, with a dramatic response to a high salt diet. Sodium supplementation was discontinued at the age of 2 years. There were 7 additional family members from 3 generations who had variable expression of PHA, ranging from asymptomatic to moderate. In affected members, pseudohypoaldosteronism persisted over 13 years; however, the plasma renin (179820) activity (PRA) decreased gradually to near-normal values. Persistent pseudohypoaldosteronism in the face of a decrease in PRA was interpreted by Hanukoglu (1991) as reflecting the development of tertiary pseudohypoaldosteronism due to autonomously functioning zona glomerulosa of the adrenal. Riepe et al. (2006) reported 7 patients presenting with isolated renal salt loss from 6 families in Italy and Germany. All manifested in early infancy with poor weight gain, failure to thrive, dehydration, or vomiting. The diagnosis of PHA1 was established by the confirmation of hyponatremia, hyperkalemia, elevated plasma renin activity or direct renin concentrations, and high plasma aldosterone levels. All patients were treated with oral sodium supplementation.

INHERITANCE

The transmission pattern in the family with PHA reported by Hanukoglu (1991) was consistent with autosomal dominant inheritance with variable expression.

MOLECULAR GENETICS

In 4 familial cases of autosomal dominant type I pseudohypoaldosteronism and in 1 sporadic patient, Geller et al. (1998) identified 4 different heterozygous mutations in the mineralocorticoid receptor gene (600983.0001-600983.0004). In affected members of a Japanese family with PHA1A, Tajima et al. (2000) found a heterozygous mutation in the MCR gene (L924P; 600983.0007). Viemann et al. (2001) reported the results of a genetic study in a sporadic case and in 5 affected patients from 2 families with autosomal dominant PHA1. In the sporadic case they identified a frameshift mutation (2871insC; 600983.0006) in exon 9 of the MCR gene. This mutation alters the last 27 amino acids of the hormone-binding domain. Sartorato et al. (2003) analyzed the NR3C2 gene in 14 families with a ... More on the omim web site

Subscribe to this protein entry history

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 177735 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).