Neonatologia
Il neonato che “sa di sale”
The “salt-tasting” newborn
ALDO RAVAGLIA1, DANIELE FRATUCELLI2, VITTORIO LONGO2
1Pediatra, ASL TO4, Torino
2Psicologo, Torino
Febbraio 2021 - pagg. 119 -122 | DOI: 10.53126/MEB40119
Abstract
Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease due to the peripheral resistance to aldosterone. Clinical spectrum with neonatal onset includes salt loss, hyponatremia, hypochloraemia, hyperkalaemia, metabolic acidosis and increased plasmatic levels of aldosterone. Two forms of the disease - renal and systemic – have been described, which are genetically distinct and with wide clinical expressivity. The most severe generalized PHA1 is caused by mutations in the genes encoding for the subunits of the epithelial sodium channels (ENaC). The paper reports the case of a newborn of the first pregnancy of healthy and consanguineous Sicilian parents, with a clinical and hormonal picture compatible with the diagnosis of generalized PHA1. A novel SCNN1A gene mutation, inherited from both heterozygous, was identified by next generation sequencing (NGS) in the homozygous child. The neonatologist should consider a diagnosis of PHA1 in case of hyponatremia, hyperkalaemia and metabolic acidosis. The diagnostic suspicion was confirmed by the increased plasmatic levels of aldosterone and aldosterone/renin ratio, associated to a poor response to steroid administration. The treatment is based on high doses of sodium chloride, fludrocortisone and glucocorticoids, insulin and ion exchange resins. It may be useful to reduce potassium intake with the use of special formulas. The clinician must gradually balance the doses of drugs on the basis of electrolyte and hormone levels. A multi-disciplinary team and close follow-up evaluations are needed for optimal management of such patients. The present report may broaden the knowledge of the genetic and molecular bases of disease, by improving its clinical characterization and providing useful indications for the treatment of patients. Clinical approach must be personalized, also in relation to long survival and potential multi-organ complications.
Riassunto
Lo pseudoipoaldosteronismo di tipo 1 (PHA1) è una rara malattia genetica caratterizzata da resistenza periferica all’aldosterone. Lo spettro clinico, a esordio neonatale, include: perdita di sali, iponatremia, ipocloremia, iperkaliemia, acidosi metabolica ed elevati livelli plasmatici di aldosterone. Si distinguono due forme, renale e sistemica, geneticamente distinte e con ampia espressività clinica. La più grave forma sistemica è causata da mutazioni nei geni codificanti per le subunità dei canali epiteliali del sodio (ENaC). Descriviamo un neonato, figlio di genitori siciliani sani e consanguinei, nato da prima gravidanza, con quadro clinico e ormonale compatibile con diagnosi di PHA1 generalizzato. Con la next generation sequencing (NGS) è stata identificata una mutazione nel gene SCNN1A, ereditata da entrambi i genitori, portatori eterozigoti della stessa mutazione, non ancora descritta e riportata in letteratura. Il neonatologo deve tenere in considerazione una diagnosi di PHA1 in presenza di iponatremia, iperkaliemia e acidosi metabolica. Il sospetto diagnostico è confermato da livelli plasmatici elevati di aldosterone, aumentato rapporto aldosterone/renina, e scarsa risposta alla somministrazione di steroidi. Il trattamento si fonda su somministrazione di sodio cloruro a dosi elevate, fludrocortisone e glucocorticoidi, insulina e resine a scambio ionico. Il clinico deve modulare gradualmente le dosi dei farmaci in base al livello di elettroliti e ormoni. Può essere utile ridurre l’intake di potassio con l’uso di formule speciali. Un team multidisciplinare e controlli ravvicinati di follow-up sono indispensabili per una gestione ottimale dei pazienti. Il nostro report può contribuire ad ampliare le conoscenze relative alle basi genetiche e molecolari della patologia, a migliorarne la caratterizzazione clinica, e fornire indicazioni utili per il trattamento di questi pazienti. L’approccio clinico deve essere personalizzato anche in relazione alla lunga sopravvivenza e alla potenziale comparsa di complicanze in vari distretti corporei.
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Corrispondenza: giocors@alice.it