Ana Cristina Simoes e Silva, Regina Maria Pereira, Frederico Jose de Carvalho Godinho, Sergio Veloso Brant Pinheiro
Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
|Address for Correspondence|
|Ana Cristina Simoes e Silva, MD, PhD; Avenida Bernardo Monteiro 1300, ap 1104, Bairro Funcionarios, 30150-281, Belo Horizonte, MG, Brazil. |
|by the lack of sensitivity to aldosterone effects (pseudohypoaldosteronism). We reported a case of life-threatening RTA-type IV manifested at neonatal period. A twelve-day-old term male neonate was admitted at emergency room of our institution with severe dehydration and without gastrointestinal losses. Laboratorial evaluation showed hyperkalemia (10mmol/L), hyponatremia (114 mmol/L) and metabolic acidosis (pH 7.23). Despite fluid and alkali replacement, the metabolic state did not recover. Adrenal congenital hyperplasia was suspected and hormone-therapy started, although without improvement. The neonate remained with hypovolemia and severe hyperkalemia (11 mmol/L). This evolution suggested a RTA-type IV, which was confirmed by elevated plasma aldosterone levels (33ng/dL, range 1-4ng/dl) with concomitant sodium urinary loss and low urinary potassium excretion (Na 38 mmol/L and K 0.7 mmol/L). It was started oral sodium and alkali replacement, hydrochlorothiazide and cation-exchange resin. Due to poor metabolic control, the patient demanded recurrent hospital admissions. At five months old, a gastrostomy tube was inserted to provide nutrition and hydroelectrolyte balance. After eight months of follow-up, the patient improved significantly his clinical condition. This case clearly illustrates the importance of early diagnosis and aggressive management for neonatal presenting forms of RTA.|
|renal tubular acidosis, hyperkalemia, metabolic acidosis, dehydration, pseudohypoaldosteronism|
|Renal tubular acidosis (RTA), the main cause of tubular dysfunction in pediatric practice, represents a clinical syndrome in which either an inherited or acquired defect leads to failure to maintain the metabolic homeostasis (1,2). It can be basically divided into three categories: distal (type I), proximal (type II) and hyperkalemic (type IV)(1,2). RTA type IV may occur both as an aldosterone deficiency or resistance to its effects. The aldosterone resistance state is a rare condition in which the basic renal defect is a lack of sensitivity to aldosterone action; hence, it is also known as pseudohypoaldosteronism(3,4). The tubular unresponsiveness leads to a reduction of potassium and hydrogen excretion and of sodium reabsorption in the presence of elevated plasma levels of aldosterone. Therefore, clinical features are extremely variable, generally including vomiting, failure to thrive, dehydration, normal anion gap metabolic acidosis, hyponatremia, and life-threatening hyperkalemia (3,5,6,7).
We report such a rare case here, including its presentation, diagnosis, treatment and evolution over eight months of follow-up, to aware the pediatricians for the importance of early detection and aggressive management of RTA in neonatal period.
|A twelve-day-old full-term male neonate, born by vaginal delivery weighting 2830 gm was admitted at emergency room of the Clinic's Hospital of the Federal University of Minas Gerais with severe dehydration without a history of gastrointestinal losses. No clinical conditions had been detected during fetal life and labor. There was no history of consanguineous marriage or family-related disorders. At admission, laboratorial evaluation showed severe hyperkalemia (10mmol/L), hyponatremia (114mmol/L) and metabolic acidosis (pH 7.23 and bicarbonate 10mmol/L). At that time, the patient was transferred to the Intensive Care Unit.
In a spite of the aggressive fluid and alkali replacement, the clinical and laboratorial state did not significantly change. A salt wasting form of congenital adrenal hyperplasia (CAH) was then suspected and a hormone replacement therapy immediately started (hydrocortisone 30mg/m2/da and fludrocortisone 0.3mg/day), though no alterations in external genitalia were observed. Even with high doses of hormones, no clinical and laboratorial improvement was accomplished. In addition, no abnormalities were detected on the adrenal steroids levels, including 17-a-hydroxyprogesterone (95ng/dl-normal range:< 200ng/dl), testosterone (170pg/ml-normal range:150-450pg/ml) and androstenedione (0.80ng/ml-normal range 0.4-2.0ng/ml).
On the 24th day of life, the patient developed an episode of hypovolemia associated with life-threatening hyperkalemia (11mmol/L) that required intravenous calcium, bicarbonate and insulin to revert electrophysiological heart effects. An aldosterone resistance form of RTA type IV was suspected due to the poor response to therapy for CAH. The lack of mineralocorticoid action was confirmed by the detection of elevated plasma aldosterone levels (33ng/dl; normal range:1-4ng/dl) associated with inappropriately high urinary sodium excretion (38mmol/L; fractional excretion of 1.5%) and a very low urinary potassium excretion (0.7mmol/L; fractional excretion of 0.8%) in 24-hour urinary sample. Plasma rennin activity (PRA) was also elevated (2.53ngAngI/ml/h-normal range:0.430±22ngAngI/ml/h). Subsequently, the patient received oral sodium chloride supplementation (1 mmol/kg every 6 hours) and alkali replacement (0.5mmol of bicarbonate/kg every 6 hours), as well as a thiazide diuretic (hydrochlorothiazide, 1.5mg/kg every 12 hours) and a cation exchange resin to control hyperkalemia.
Even after appropriated treatment, the patient presented recurrent episodes of metabolic disarrangements with deterioration in nutritional state and also systemic infections that continuously demanded hospital care and adjustments of fluid and electrolyte replacement therapy. During the last hospitalization, when the patient aged 5 months old, a gastrostomy tube was inserted to improve nutrition and to allow adequate administration of fluids, electrolytes, alkalis and medications. This procedure succeeded in avoiding clinical worsening and new hospital admissions. In addition, a good metabolic control was achieved with sodium citrate solution (2g, 2 times per day), sodium chloride (10mEq/kg/day), sodium bicarbonate (5mEq/kg/day), hydrochlorothiazide (0.5mg/kg/day), and cation exchange resin (1g, 2 times per day). After eight months of follow-up, the infant significantly improved his clinical condition and recovered body growth and nutritional state.
|We report a case of a male neonate with clinical and laboratorial features highly suggestive of CAH at first sight. Since it is relatively common, the hypothesis of salt-wasting form of CAH should be considered in all neonate with hyponatremia coupled to hyperkalemia (8). The salt-wasting form can be basically caused by two enzymatic deficiencies: 21-hydroxylase, the most common, and 3b-hydroxysteroid-dehydrogenase, a very rare defect. Both result in cortisol and aldosterone deficiencies with different plasma levels of sex hormones. Glucocorticoid and mineralocorticoid replacement therapy and sodium supplementation usually provide adequate indices of metabolic control (8).
Despite the use of high doses of hormones and electrolyte and fluid replacement, the patient continuously exhibited recurrent episodes of dehydration, severe hyperkalemia, hyponatremia and metabolic acidosis, suggesting the possibility of mineralocorticoid unresponsiveness. Moreover, cortisol and mineralocorticoid precursors were within normal range, making highly improbable the possibility of CAH. Thus, the rare diagnosis of aldosterone resistance form of RTA type IV was subsequently confirmed by the detection of high plasma levels of aldosterone and also of PRA.
Aldosterone resistance state, also known as pseudohypoaldosteronism, has been coined to describe disorders of electrolyte homeostasis characterized by a condition of renal tubular lack of sensitivity to aldosterone (3,6,9,10). There are two subtypes. Type 1 is a hereditary disorder related to the loss of function of the mineralocorticoid receptor. In recent years, it has become clear that type 1 pseudohypoaldosteronism (PHA1) is a heterogeneous syndrome that includes at least two clinically and genetically distinct entities with either renal or multiple target-organ defects (1,3,11,12). Type 2 pseudohypoaldosteronism (PHA2), also recognized as Gordon's Syndrome, is thought to be a primary renal secretory defect that results in enhanced chloride reabsorption and consequent hyperkalemia, metabolic acidosis, and low-renin arterial hypertension (3,13).
Renal PHA1 represents the most frequent form of pseudohypoaldosteronism and is related to the loss of function of the mineralocorticoid receptor. The mode of inheritance is autosomal dominant with variable expression, although many cases appear as sporadic. The reasons for phenotype differences are unknown, but they may be related to intercurrent volume-depleting events or to dietary habits of salt ingestion during life (1,3,12). In addition, the co-existence of polymorphism or mutations in the gene encoding epithelial sodium channel could play a potential role. The severity of clinical and laboratorial manifestations at the time of the diagnosis is inversely correlated to the age of the patient, ranging from a neonatal life-threatening salt wasting syndrome to an adult asymptomatic elevation of plasma aldosterone levels (12). The presence of urinary salt wasting, dehydration, metabolic disarrangements, normal blood pressure, preserved glomerular filtration function, elevated aldosterone levels and high PRA supported the diagnosis of a sporadically form of renal PHA1 for the case reported here. Although family history did not reveal additional early neonatal deaths or symptoms suggestive of PHA in three generations, we cannot exclude the possibility of a partial form with mild course of the disease among the relatives.
Multiple target-organ PHA1 is due to defective sodium transport in many organs containing epithelial sodium channel such as kidney, lung, colon, and exocrine glands. This variant is inherited as an autosomal recessive disorder, with uniform expression. Although no studies involving sweat electrolyte levels, gastrointestinal sodium excretion were performed, the satisfactory response to sodium replacement therapy pointed out to renal PHA1 and made unlikely the diagnosis of a multiple target organ PHA1.
In renal PHA1 patients, salt supplementation frequently restores metabolic control and catches-up growth (2,5,9,12). Some studies reported that the improvement might occur beyond one to three years of age. In spite of initial difficulties to obtain metabolic control, the follow-up of this infant showed a marked clinical recovery. This case clearly illustrates that neonatal presentation of renal PHA1 represents a severe condition that requires early diagnosis and aggressive therapy.
Last Updated : Saturday, March 01, 2008 Vol 5 Issue 3 Art #11
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|Silva e S C A, Pereira M R, Godinho C d J F, Pinheiro B V S. NEONATAL PRESENTATION OF RENAL TUBULAR ACIDOSIS TYPE IV - A CASE REPORT . Pediatric Oncall [serial online] 2008[cited 2008 March 1];5. Art #11. Available From : http://www.pediatriconcall.com/Journal/Article/FullText.aspx?artid=88&type=J&tid=&imgid=&reportid=133&tbltype=|