medwireNews: Researchers report that good outcomes are possible for children with autosomal recessive pseudohypoaldosteronism type 1 (PHA1B), despite its high morbidity and mortality risk.
Indeed, one of their female patients, who they say is only the second PHA1B patient reported to have survived until their fourth decade, achieved a successful pregnancy at the age of 28 years, albeit with preterm delivery.
Nicholas Shaw (Birmingham Women and Children’s NHS Foundation Trust, UK) and colleagues report data from 12 children with PHA1B, which they say is the largest case series published to date.
The children, who included four sibling pairs, were South Asian, Yemeni, or Sudanese, and all were born to consanguineous parents. The study authors note that three of the families had unexplained neonatal deaths.
All patients presented within the first 2 weeks of life, primarily with vomiting, poor feeding or weight loss. Three had evidence of circulatory collapse. They remained in hospital for between 12 days and 2 years.
Shaw and team found the largest risk to the children was unstable hyperkalaemia, which led to cardiac arrest in eight children and cardiac arrhythmias (supraventricular and ventricular tachycardia, and ventricular fibrillation) in three.
Three of the cardiac arrests, which occurred when the children were aged 3 years or less, were followed by “profound neurodevelopmental sequelae”, with two children later dying. However, the other five children with cardiac arrests or arrhythmias had normal neurological outcomes.
“Based on our experience of 12 patients over 37 years, the risk of death before the 3rd decade is 25%, and the risk of severe neurological impairment before 4 years of age is 33%”, say the researchers.
They note: “Morbidity and mortality is high in the younger age groups, and in older individuals with associated neurodevelopmental impairment, because recognition of acute illness by carers may be delayed.”
One child had neurodevelopmental issues not related to cardiac arrest, and seven children had feeding problems related to nasogastric tube feeding or gastrostomy, which lasted up to 20 years.
Five children had recurrent blepharoconjunctivitis related to excessive salt in tears, five had recurrent respiratory infections and two had hypertension, which the researchers attribute to salt treatment.
Ongoing treatment with high-dose sodium chloride and sodium bicarbonate was given initially via nasogastric tube or gastrostomy, due to “[u]npalatability and large volumes”, say the researchers, but three patients switched to tablets and capsules between the ages of 6 and 19 years.
“Whilst sodium requirements are high in early childhood they do stabilize and progressively reduce with age, but increased requirements of 5–10 mmol/kg/day remain into adulthood”, the team writes in the European Journal of Endocrinology.
Following successful use of the ion-exchange resin sodium resonium to achieve electrolyte stability and hospital discharge in one patient, this was used as standard therapy in all patients.
“From our experience, having emergency strategies in place avoids complications and improves survival”, say Shaw and team.
They add: “In addition to provision of detailed patient information in relation to warning signs, genetic information about inheritance can ensure screening and early disease detection in future offspring and genetic counselling.”
By Eleanor McDermid
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Eur J Endocrinol 2021; doi:10.1530/EJE-20-0152