title: Pseudohypoaldosteronism type 1: clinical features and management in infancy.
abstract: Type 1 pseudohypoaldosteronism (PHA) is a rare heterogeneous group of disorders characterised by resistance to aldosterone action. There is resultant salt wasting in the neonatal period, with hyperkalaemia and metabolic acidosis. Only after results confirm isolated resistance to aldosterone can the diagnosis of type 1 PHA be confidently made. Type 1 PHA can be further classified into i) renal type 1 (autosomal dominant (AD)) and ii) multiple target organ defect/systemic type 1 (autosomal recessive (AR)). The aim of this case series was to characterise the mode of presentation, management and short-term clinical outcomes of patients with PHA type 1. Case notes of newly diagnosed infants presenting with PHA type 1 were reviewed over a 5-year time period. Seven patients were diagnosed with PHA type 1. Initial presentation ranged from 4 to 28 days of age. Six had weight loss as a presenting feature. All subjects had hyperkalaemia, hyponatraemia, with elevated renin and aldosterone levels. Five patients have renal PHA type 1 and two patients have systemic PHA type, of whom one has had genetic testing to confirm the AR gene mutation on the SCNN1A gene. Renal PHA type 1 responds well to salt supplementation, whereas management of patients with systemic PHA type 1 proves more difficult as they are likely to get frequent episodes of electrolyte imbalance requiring urgent correction.
  
  
  CONCLUSIONS
  Patients with type 1 PHA are likely to present in the neonatal period with hyponatraemia, hyperkalaemia and metabolic acidosis and can be diagnosed by the significantly elevated plasma renin activity and aldosterone levels.The differential diagnosis of type 1 PHA includes adrenal disorders such as adrenal hypoplasia and congenital adrenal hyperplasia; thus, adrenal function including cortisol levels, 17-hydroxyprogesterone and a urinary steroid profile are required. Secondary (transient) causes of PHA may be due to urinary tract infections or renal anomalies; thus, urine culture and renal ultrasound scan are required respectively.A differentiation between renal and systemic PHA type 1 may be made based on sodium requirements, ease of management of electrolyte imbalance, sweat test results and genetic testing.Management of renal PHA type 1 is with sodium supplementation, and requirements often decrease with age.Systemic PHA type 1 requires aggressive and intensive fluid and electrolyte management. Securing an enteral feeding route and i.v. access are essential to facilitate ongoing therapy.In this area of the UK, the incidence of AD PHA and AR PHA was calculated to be 1:66 000 and 1:166 000 respectively.
authors.affiliation: Paediatric Endocrinology Leeds Teaching Hospitals Leeds General Infirmary, Leeds UK.
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authors.lastname: Amin
authors.affiliation: Paediatric Endocrinology Leeds Teaching Hospitals Leeds General Infirmary, Leeds UK.
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authors.initials: NS
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authors.affiliation: Clinical Chemistry Leeds Teaching Hospitals Leeds UK.
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authors.initials: JH
authors.lastname: Barth
authors.affiliation: Clinical Chemistry Leeds Teaching Hospitals Leeds UK.
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authors.affiliation: Paediatric Nephrology Leeds Teaching Hospitals Leeds UK.
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authors.affiliation: Paediatric Nephrology Leeds Teaching Hospitals Leeds UK.
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authors.affiliation: Paediatric Medicine Bradford Teaching Hospitals Bradford UK.
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authors.affiliation: Paediatric Medicine Airedale General Hospital Keighley UK.
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authors.affiliation: Paediatric Endocrinology Sheffield Children's Hospital Sheffield UK.
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authors.affiliation: Paediatric Endocrinology Sheffield Children's Hospital Sheffield UK.
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authors.lastname: Makaya
authors.affiliation: Paediatric Endocrinology Leeds Teaching Hospitals Leeds General Infirmary, Leeds UK.
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authors.lastname: Mushtaq