Anzeige
Erschienen in:
03.02.2022 | Clinical Quiz
Persistent mild hypokalemia in an otherwise healthy 6-year-old girl: Answers
Erschienen in: Pediatric Nephrology | Ausgabe 8/2022
Einloggen, um Zugang zu erhaltenExcerpt
1.
Which diseases should be considered in the differential diagnosis of this patient?
Hypokalemia may result from inadequate potassium intake, shift of potassium (K) from the extracellular to the intracellular space, or increased potassium excretion from the gastrointestinal tract, the kidneys, and the skin [1].
In order to determine the origin of this girl’s hypokalemia, the urinary K level was measured. The random urinary K level was elevated (Table 1). In the setting of serum K levels of < 3 mEq/l, a random urinary K level of > 15–20 mEq/l suggests excessive renal potassium loss [2], and this was the case in our patient. The fractional excretion of magnesium (FEMg) in urine was slightly elevated (Table 1).
Excessive renal potassium loss can be due to renin and aldosterone disturbances, increased distal flow in the kidney due to diuretic use, hypomagnesemia, osmotic diuresis, drug nephrotoxicity, renal tubular acidosis I or II, or genetic tubular disorders (Bartter syndrome, Gitelman syndrome) [1].
2.
What is the most likely diagnosis?
Increased mineralocorticoid activity was ruled out in this patient since she did not present hypertension, and her aldosterone level, 25 ng/dl, was normal (NR 2–70 ng/dl), but her renin level, 97.8 pg/ml, was raised (NR in the upright position 1.3–13.8 pg/ml). The normal aldosterone level and BP excluded a secreting adenoma and familial hyperaldosteronism type 1, a hereditary condition known as apparent mineralocorticoid excess (AME) syndrome. In the absence of acid–base disturbances, renal tubular acidosis I and II were ruled out.
The levels of adrenocorticotropic hormone (ACTH), 12.3 pg/ml (NR 10–60 pg/ml); cortisol, 21.2 ng/dl (NR 5–25 ng/dl); and dehydroepiandrosterone (DHEAS), 6.9 μg/dl (pre-pubertal NR < 40 μg/dl) were all normal.
Regarding increased distal flow as the cause of hypokalemia, this patient was not taking diuretics, mannitol, or any other drug with an osmotic effect. Her serum Mg levels were within the NR, but an increase in urine Cl excretion was detected (Table 1). Urinary Cl levels of > 40 mEq/l, in combination with alkalosis, would indicate the diagnosis of Bartter or Gitelman syndrome [3], as was the case in our patient, but this patient did not present alkalosis.
Bartter syndrome is an autosomal recessive renal tubular disorder, characterized by hypokalemia, hypochloremia, normomagnesemia, increased or normal urinary calcium excretion, metabolic alkalosis, and hyperreninemia, with normal BP [4, 5].
Gitelman syndrome is an autosomal recessive disorder which presents with hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and low BP [6].
Twenty-four-hour urinary Ca excretion of > 4 mg/kg/24 h or a Ca/Cre ratio in a random urine sample (UCa/UCre) of > 0.2 mg/mg indicates hypercalciuria [7], which is compatible with Bartter syndrome. In contrast, urinary calcium excretion in Gitelman syndrome is usually in the lower NR [8], as in this patient (Table 1).
According to these findings, atypical Gitelman syndrome appeared to be the most likely diagnosis for this girl.
3.
What investigations would you perform to reach a definitive diagnosis?
Genetic testing is the gold standard for making a definitive diagnosis. This was performed by whole exome sequencing, which revealed a homozygous mutation in the SLC12A3 gene, thus establishing Gitelman syndrome as the conclusive diagnosis. Specifically, in exon 22 of the SLC12A3 gene in the location 2612, a guanine was replaced by a cytosine. As a result, in location 871 of the produced protein, the arginine was substituted by proline (SLC12A3:NM_000339.3:exon22:c.2612G > C:p.R871P).
4.
How should this patient be treated?
Following the definitive diagnosis, potassium supplement was administered to the patient in the form of KCl 10%, in a dose of 2 mmol/kg/24 h, together with free fluid consumption and potassium-rich foods. The laboratory findings at follow-up at 6 and 12 months are shown in Table 1. At the last follow-up (12 months from onset), adjustment of the KCl dosage was made, and magnesium pidolate supplementation was given in a dose of 4.6 mEq/kg/24 h, due to onset of hypomagnesemia (Table 1).
Table 1
Laboratory findings in the 6-year-old girl with mild hypokalemia at the onset and at follow-up, 6 and 12 months from the onset
|
Laboratory results
|
At the onset
|
At 6 months
|
At 12 months
|
|---|---|---|---|
|
Serum Cre (mg/dl) (NR 0.3–0.7)
|
0.49
|
0.50
|
0.51
|
|
Serum urea (mg/dl) (NR 10–36)
|
29
|
23
|
22
|
|
Serum K (mEq/l) (NR 3.4–4.7)
|
3.05
|
3.3
|
2.9
|
|
Serum Na (mEq/l) (NR 135–145)
|
138
|
136
|
136
|
|
Serum Cl (mEq/l) (NR 98–107)
|
100
|
99
|
99
|
|
Serum Mg (mEq/l) (NR 1.3–2.0)
|
1.56
|
1.50
|
1.28
|
|
pH (NR 7.35–7.45)
|
7.37
|
7.43
|
7.40
|
|
HCO3− mEq/l (NR 20–26)
|
21.5
|
24.3
|
24.0
|
|
Random urinary K (mEq/l)
|
67
|
20
|
69
|
|
Random urinary Cl (mEq/l)
|
53
|
24
|
51
|
|
FEMg (%)
|
4.7
|
6.76
|
3.17
|
|
Random urinary Ca/Cre (mg/mg) (NR < 0.2)
|
0.02
|
0.036
|
0.007
|
|
24-h urine Ca excretion (mg/kg/24 h) (NR < 4)
|
0.4
|
-
|
0.54
|