CORE Metadata, citation and similar papers at core.ac.uk Provided by MUCC (Crossref) Hindawi Case Reports in Pediatrics Volume 2017, Article ID 7939854, 8 pages https://doi.org/10.1155/2017/7939854 Case Report Systemic Pseudohypoaldosteronism Type I: A Case Report and Review of the Literature Nasifa Nur,1 Cameron Lang,2 Juanita K. Hodax,1 and Jose Bernardo Quintos1 1 Division of Pediatric Endocrinology, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, USA 2Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, USA Correspondence should be addressed to Jose Bernardo Quintos; [email protected] Received 7 September 2016; Revised 15 February 2017; Accepted 19 March 2017; Published 18 April 2017 Academic Editor: James Stockand Copyright © 2017 Nasifa Nur et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Systemic pseudohypoaldosteronism (PHA) type I is a rare genetic disorder resulting from mutations in the subunits of the epithelial sodium channel that manifests as severe salt wasting, hyperkalemia, and metabolic acidosis in infancy. In this article we report a patient with systemic PHA type I presenting with severe dehydration due to salt wasting at 6 days of life. She was found to have a known mutation in the SCNN1A gene and subsequently required treatment with sodium supplementation. We also review the clinical presentation, differential diagnosis, and treatment of systemic PHA type I and summarize data from 27 cases with follow-up data. 1. Introduction described PHA in 1958 [5]. Since then, several patients have been reported and our understanding of the disease Pseudohypoaldosteronism (PHA) type I is a rare salt wasting has expanded dramatically. Here we report a patient with syndrome caused by aldosterone resistance with two distinct systemicPHAtypeIandreviewtheliteratureonthisdisease forms: an autosomal dominant type, caused by a mutation including the clinical presentation, differential diagnosis, of the mineralocorticoid receptor with sodium wasting in genetic diagnosis, treatment, and follow-up data. the kidney, and an autosomal recessive form, resulting from mutations in one of the 3 subunits (alpha, beta, or gamma) + 2. Case Report of the epithelial Na channel(ENaC)[1,2].TheENaC channelallowstheflowofsodiumfromthelumeninto A 6-day-old girl presented with vomiting, lethargy, and the epithelial cell and modulates the amount of sodium in severe dehydration. Physical examination showed an ill the extracellular fluid [2]. The autosomal dominant form, appearing infant with pale skin, poor perfusion, and sunken also known as renal PHA type I, is confined to the kidney eyes. She was born full-term with birth weight 3.0 kg to with less severe disease and no systemic involvement. In the consanguineous parents of Pakistani origin, with preg- autosomal recessive form, also known as systemic PHA type nancy complicated only by gestational diabetes requiring I, patients have multisystem disease with sodium wasting insulin. She had normal genitalia without clitoromegaly, in the kidney, lungs, colon, sweat, and salivary glands. As labial fusion, or hyperpigmentation and no palpable abdomi- + a result of decreased sodium-dependent liquid absorption nal mass. Laboratory evaluation showed hyponatremia Na + in the lungs, children often develop pulmonary symptoms 124 mEq/L, hyperkalemia K 10 mEq/L, metabolic acidosis − + including congestion, wheezing, and recurrent pulmonary HCO3 10 mEq/L, urine Na 150 mEq/L, elevated serum infections. Renal PHA type I is generally milder and tends aldosterone 8.97 nmol/L (normal range 0–6 nmol/L for term to remit with age, whereas systemic PHA type I persists infants), plasma renin activity 13.39 ng/mL/hr (normal range and requires lifelong treatment [2–4]. Cheek and Perry first 2–35 ng/mL/hr for infants 1–7 days, though some labs 2 Case Reports in Pediatrics use reference range 1.4–7.8ng/mL/hr for this age), normal NaHCO3 supplements at a total dose of 60 mEq/kg/day of serum cortisol 634.8 nmol/L (normal >500 nmol/L during sodium. Genetic testing revealed the same SCNN1A mutation acute stress), and normal 17-hydroxyprogesterone 0.7 nmol/L as her sister described above, confirming the diagnosis of (normal range 0.2–2.3 nmol/L for term infants). A sweat systemic PHA type I. Her course was uncomplicated and she − test showed elevated sweat Cl 34 mEq/L (normal range was discharged from the NICU at 10 days of life. Sodium 0–29 mEq/L for infants 0–4 months). She had a normal renal doses were titrated based on serum levels with eventual ultrasound. decreaseto26mEq/kg/dayofsodiumby21daysoflife. She required two normal saline boluses, oxygen, and several doses of Kayexalate and NaHCO3 as well as an insulin 3. Review of Literature drip and glucose to correct electrolyte abnormalities. Sodium and potassium normalized within 2 days. She subsequently 3.1. Clinical Presentation. Systemic PHA type I typically developed right lower lobe pneumonia requiring antibiotics presents in the neonatal period with severe salt wasting crisis and intubation, as well as Klebsiella and Enterococcus sepsis with hyponatremia, hyperkalemia, acidosis, and dehydration from her femoral line. She was discharged from the hos- due to sodium loss through the kidney, colon, sweat, and sali- pital after 4 weeks but then developed ventricular tachy- vary glands [4]. Patients may also present with lethargy and cardia requiring cardioversion due to hyperkalemia with + failure to thrive. Hyponatremia and hyperkalemia are com- K >9 mEq/L. Potassium levels normalized after increasing bined with elevated plasma renin activity and aldosterone Kayexalate. She was then maintained on sodium supplemen- levels reflecting renal resistance to aldosterone. Recurrent tationof49mEq/kg/dayaswellasKayexalate3gramsevery salt wasting crises and severe hyperkalemia can lead to life- 8hours. threatening cardiac arrhythmias and cardiac arrest. Patients Full sequencing of the SCNN1A gene that encodes the may present with symptoms similar to cystic fibrosis such alpha subunit of ENaC was performed at Johns Hopkins as elevated sweat chloride secretion, failure to thrive, and University. Reported test methods were DNA extraction recurrent pulmonary infections [24]. In systemic PHA type from whole blood, amplification of the coding sequence I defects in the ENaC channel lead to decreased sodium- of SCNN1G by polymerase chain reaction in 14 segments, dependent liquid absorption, which leads to excess liquid cycle sequencing of each segment in the forward and reverse in the airway lumen causing narrowing of the airway and directions, and analysis of each sequence by capillary elec- predisposing patients to wheezing and airway infections [24]. trophoresis. This showed a known mutation Nt1685C->T Systemic PHA type I has also been reported to present causing replacement of leucine for serine at position 562 in with pustular miliaria rubra, which is characterized by itchy exon 13, which forms the 2nd transmembrane subunit of the eruptions affecting mainly the trunk and limbs appearing alpha chain of ENaC. This mutation was previously reported within the first few months of life [25]. This is thought to in a patient with systemic PHA type I [11] and confirmed the be due to sweat gland duct occlusion and inflammation of diagnosis in our patient. The testing was unable to determine eccrine glands as a result of sodium accumulation, as ENac if the mutation was present in two copies (homozygous) or isexpressedstronglyineccrineglandsaswellasmultiple one copy with a deletion of the 2nd allele (hemizygous). epidermal layers [25, 26]. Sequencing of parental genes was not done. The patient began developing the characteristic pul- 3.2. Differential Diagnosis. Initial presentation of systemic monary symptoms at age of 2 years with recurrent pneumo- PHA type I may be confused with salt wasting congenital nia related to chronic bronchorrhea requiring intermittent adrenal hyperplasia (CAH), renal PHA type I, secondary treatment with Atrovent (Ipratropium). She had 7 episodes of PHA, or renal tubular acidosis (RTA) type IV. Salt wasting pneumonia between ages of 2 and 3 years. These symptoms CAH due to 21-hydroxylase deficiency leads to cortisol and improved with age and frequency of infections decreased. aldosterone deficiency. Aldosterone deficiency leads to the Repeat sweat test at age of 3 years showed elevated sweat same presenting symptoms as the aldosterone resistance that − Cl 133 mEq/L (normal range 0–39 mEq/L for patients >4 is characteristic of systemic PHA type I. Females with salt months). At her last follow-up at 5 and 5/12 years of age, she wasting CAH are born with virilized genitalia due to elevated was receiving Kayexalate, NaCl, and NaHCO3 for a total dose androgen levels, but males with salt wasting CAH have of 23 mEq/kg/day of sodium. She has not had any recurrent normal genitalia. Patients with systemic PHA type I typically salt wasting crises. Her height was 103.8 cm (−1.5 SDS), weight have normal genitalia, making males presenting with salt 2 13.4 kg (−3.1 SDS), and BMI 12.4 kg/m (−3.2 SDS). Labs at wasting particularly difficult to differentiate between CAH + that time showed normal electrolytes with Na 135 mEq/L and systemic PHA type I based on clinical presentation alone. + and K 4.4 mEq/L. Renal PHA type I may present with similar symptoms as The patient had 2 younger siblings born to the same systemic PHA type I, but it is less severe, limited to renal mother and father. The first sibling was clinically unaffected, saltwasting,andsymptomsimprovewithage[6].Apositive and genetic testing showed that he was a carrier of the sweat or salivary sodium level can confirm the diagnosis mutation in the SCNN1A gene. The second sibling developed of systemic PHA type I and can differentiate this from + + − salt wasting with Na 131 mEq/L, K 7.