Hyperkalemic distal renal tubular acidosis associated with Rett syndrome

Abstract

Renal function was studied in a 7-year-old girl with Rett syndrome (RS) complicated by persistent hyperchloremic hyperkalemic metabolic acidosis. The acidosis was associated with a urine pH above 5.5, positive urinary anion gap and decreased potassium excretion. Plasma renin activity, aldosterone and cortisol levels were normal. Therapy with sodium bicarbonate failed to lower urine pH below 5.5 or increase potassium excretion. Hydrochlorothiazide administration resulted in a fall in urine pH below 5.5 and an increase in potassium excretion as a result of increased distal sodium delivery and increased sodium reabsorption in the distal nephron. We conclude that a voltage-dependent type of derangement in the distal nephron, rather than aldosterone deficiency, is responsible for the impairment in urinary acidification observed in this patient. Early detection of impaired renal acidification in RS may prevent or slow the progression of growth failure.

Rett syndrome: think outside the (skull) box

“…Urological dysfunction is infrequent but is described in a subset of patients, about 8% of a large cohort of 905 girls with typical RTT 87 , which is a higher incidence rate compared with the general population. The most frequent complications are urinary tract infection, kidney stones, or urine retention 87 but also urinary acidification 88 . These symptoms are significantly correlated with the total clinical severity score.…”

Rett syndrome: a neurological disorder with metabolic components

“…Given the association between MeCP2 and HDAC3, non-specific HDAC inhibitors, commonly prescribed for seizure maintenance, should be approached cautiously as a treatment in RTT. Additionally, both RTT patients and Mecp2 mutant mice present with metabolic syndrome [ 15 , 180 ], oxidative stress [ 27 , 29 ], cardiac defects [ 211 , 212 ], decreased bone density [ 174 , 213 ] and urological dysfunction [ 214 , 215 ]. As CNS-targeted gene therapy becomes a more realistic therapeutic approach, peripheral deficiency of MeCP2 must be considered more than ever as these symptoms are likely to persist following targeted genetic treatment to the brain.…”