An infant’s failure to thrive ended in death

Discussion

Due to urinary tract outlet obstruction in the form of urethral valves, the patient contracted a urinary tract infection which developed into a life-threatening systemic infection. Additionally, the endocrine condition pseudohypoaldosteronism (PHA) arose, which may explain some of the symptoms displayed before and during the dramatic septic event. Our assertion is that transient pseudohypoaldosteronism is a neglected condition in infants with obstructive uropathies. This is not a frequent condition in infants, but the consequences may be serious unless the diagnosis is established in time and treatment is directed at the underlying cause. The condition is normalised by surgical correction of the obstructive uropathy.

Pseudohypoaldosteronism may be familial but is normally transient, arising as a consequence of a urinary tract obstruction. Paradoxically, all forms of this condition display extremely high levels of plasma aldosterone. The mechanism is probably an ACTH-mediated compensatory synthesis of aldosterone caused by a reduced aldosterone response in the distal kidney tubules (Figure 2). Due to the salt loss, the children’s weight gain is poor and they demonstrate a general failure to thrive. Hyperkalaemia is also found to varying degrees, as is metabolic acidosis, water loss and compromised peripheral circulation (fig 2) (1) – (5).

In 1958, Cheek & Perry described a familial form of pseudohypoaldosteronism in infancy as a salt-losing condition with normal kidney and adrenal gland functions, later known as PHA type I for which cyanosis is described as an initial symptom (2). Phenotypically, the condition displays either a renal or a generalised form of aldosterone resistence, the former with a mild clinical progression accompanied by light hyponatraemia, the latter with more complex symptoms involving aldosterone resistance in monocytes, lymphocytes, salivary glands, sudoriferous glands and kidney tubules (6, 7).

Like PHA type I, PHA type II is also familial; it is, however, rarer (8). PHA type II is differentiated from PHA type I by hypertension, low renin levels, and a hyperchloremic rather than a hypochloremic metabolic acidosis without salt loss (tab 2). For PHA type II, sodium restriction is therefore recommended, while PHA type I is treated with sodium supplements (Table 3).

Our patient suffered from none of the familial forms, but rather the transient form first described by Rodrìguez-Soriano et al. in 1983 (9). Four of six patients in their material were associated with obstructive uropathy. The obstructive uropathy may be caused by ureteropelvic junction stenosis, bilateral terminal ureteral stenosis, ectopic ureterocele, meatal stenosis and not least – urethral valves. In a wider sense, vesicoureteral reflux is also included among the obstructive uropathies because the condition causes increased pressure in the kidney pelvis (10, 11). Transient pseudohypoaldosteronism has been described by many (4, 10) – (13); the condition manifests itself after the neonatal period with vague symptoms in the form of slow weight gain, signs of failure to thrive, and gradually also vomiting and dehydration. Failure to thrive and poor weight gain are also symptoms of congenital heart disease, congenital metabolic disease or less serious conditions such as poor breast feeding techniques and hypertrophic pyloric stenosis. One case report described the condition as hypertrophic pyloric stenosis, probably caused by a urinary tract infection (14). Undiagnosed, transient pseudohypoaldosteronism may progress into the fulminant form, presenting with salt-losing nephropathy accompanied by hyperkalaemia, hyponatraemia and normochloremic or hypochloremic metabolic acidosis (fig 2). The condition is diagnosed by extremely high plasma aldosterone levels and renin activity, both of which are reversible by correcting the obstructive uropathy (Figure 2). However, one instance of persistent pseudohypoaldosteronism is described, caused by unilateral kidney dysplasia following a vesicoureteral reflux (3).

Our patient had a pneumothorax at birth. The connection between spontaneous pneumothorax at birth and obstructive urinary tract anomaly is well known (15, 16). A possible cause may be pulmonary hypoplasia after varying degrees of oligohydramnios (17, 18). Spontaneous pneumothorax has also been described in connection with transient pseudohypoaldosteronism (19). We suggest that any spontaneous pneumothorax in fully gestated infants who have not been exposed to positive pressure ventilation should instigate an assessment for potential urinary tract anomalies, with or without pseudohypoaldosteronism.

Transient pseudohypoaldosteronism may occur even if there is no obstructive uropathy, as is the case with pyelonephritis (13). The biochemical changes described for pyelonephritis are similar to those described for a normocalcemic pseudohypoaldosteronism with sodium in the lower normal range at the initial stages of infection, and with persistent high levels of renin and aldosterone in patients with scarring established by DMSA scintigraphy (20). Some authors will therefore maintain that the infection is the cause of the pseudohypoaldosteronism, not the obstructive uropathy (21). Tables 2 and 3 show biochemical profiles and treatment profiles for various types of the condition as well as some relevant differential diagnoses.

We conclude that in infants, vague symptoms such as poor weight gain and failure to thrive may be caused by transient pseudohypoaldosteronism secondary to obstructive uropathy. Coupled with secondary infection spread from the urinary tract, the condition may contribute to the development of circulatory collapse. Helpful diagnostic tests include blood pressure measurements, measurements of electrolytes in blood and urine, ultrasound examination of the urinary tract and measurements of plasma renin activity and plasma aldosterone levels. However, in an infant it is of paramount importance to discover an obstructive uropathy in time.