Bartter Syndrome Type 3 – Clinician Information

  • Background

    Type 3 Bartter syndrome (T3BS) is, like Gitelman syndrome (GS), typically characterized by hypokalemic metabolic alkalosis but in contrast, there is often no significant hypomagnesemia and urinary calcium excretion may be low, normal or high.

    T3BS may appear in childhood, but is more frequently diagnosed in adolescence or adulthood. Symptoms are widely variable both in nature and severity. The commonest are lethargy, transient weakness and/or tetany, paresthesiae, thirst and joint pains due to chondrocalcinosis. Blood pressure is usually lower than normal. Sudden cardiac arrest may occur.

    Because of this variability, management cannot be protocol driven and must be individualized according to response and biochemical severity.

    Mutations in CLCNKB, encoding the loop’s basolateral chloride transporter, are found in T3BS patients, whereas GS is associated with SLC12A3 mutations.

    CKD can become a problem in T3BS, but is not usually a feature of GS.

  • Clinical Diagnosis

    Ask about:

    • lethargy, muscle weakness/pain, paresthesiae, tetany (all may be variable/transient)
    • palpitations
    • thirst/polydipsia, salt craving (usually patients prefer salty to sweet treats in childhood)
    • polyuria/eneuresis
    • joint pain
    • diuretic/laxative/PPI use, (whether prescribed or over-the-counter).

     

    Measure:

    • blood K (low)
    • Mg (may be normal or low)
    • Bicarb (>25)

    Send spot urine calcium:creatinine ratio or 24 hour urine calcium collection (low, normal or high)

    BP:  low but rises with age

    Refer to regional centre  if ≥ 3 abnormalities and not on above drugs

    Further investigations:

    • renin / aldosterone (raised / raised if K not low)
    • diuretic / laxative screen
    • urine Cl if diagnosis doubtful (low in vomiting/laxative abuse)
    • renal u/s (T3BS patients may have nephrocalcinosis; those with GS do not)
    • genetic testing (see below)
  • Management

    1.   Support electrolytes directly (lifelong) Requirements for K / Mg are variable and must be individually tailored, and may be very high.

    Salt: encourage liberal addition of salt to food, and high potassium/magnesium diet.

    Potassium: KCl better than effervescent K.  Can be given as tabs or liquid. Usually less symptomatic if K >3. K will not rise until Mg does. SlowK™ and Kay-Cee-L Liquid™ are preferable to SandoK™. SlowK is currently not available. A prescription for “slow release KCL 600 mg” with the dose will enable pharmacists to obtain an equivalent through IDIS.

    Magnesium: This is difficult as all Mg preparations cause diarrhoea and they differ in bio-availability.

    • Aim for Mg > 0.6 to minimise symptoms. Trial and error (from a starting point of Mg glycerophosphate or lactate at 3–5 mg/kg/24 hrs, divided in 2–4 doses) is necessary.
    • Mg Lactate: (Magtab SR) is slow-release and often better tolerated/more effective, therefore dosage lower. It also only requires twice daily prescription in most cases.
    • A few patients require intermittent iv Mg and/or K boluses; however benefits may be short-lived.

    Over dosage of K/Mg is very unlikely unless CKD coexists. Patient tolerance is the usual limiting factor.

    Doses usually require increase during periods of intercurrent infections, especially those involving vomiting and diarrhoea. In case of acute tetany, 20% MgCl2 should be administered IV (0.1 mmol Mg/kg per dose) every 6 hours prn, together with K as necessary.

    (See Dietary Needs)

    2.     Support electrolytes indirectly (individualise)

    K:       amiloride, spironolactone/eplerenone, ACE inhibitors/ARBs, beta blockers.
    Mg:    amiloride

    Can be useful to decrease electrolyte requirements. Doses often limited by BP drop and/or other side effects

    3.   Other

    •  Vitamin D (may help Mg)
    • Investigate cardiac rhythm symptoms w/ 24 hour tape
    • Maintain a high salt and high potassium diet
    • May require NSAIDs for chondrocalcinosis (indomethacin NOT otherwise indicated)

     

    Guidelines approved by the Renal Association and the Royal College of Anaesthetists for the perioperative management of people with inherited saltwasting alkaloses (Gitelman’s syndrome and Bartter’s syndrome) undergoing non-urgent surgical procedures have now been published can be viewed online here.

  • Monitoring

    1-2 x yearly at regional centre.

    Plus 1-3 monthly K, Mg, bicarb measurements at local centre/GP, more often if any instability.

    At each visit complaints related to hypokalemia (fatigue, muscle weakness, constipation, cardiac arrhythmias) and hypomagnesemia (tetany, cramps, paresthesias, joint and muscle pain) should be evaluated.

    Patient self-care

    T3BS patients should be encouraged to keep their own results tables and increase K/Mg doses as a first-line if unwell. Like people with diabetes, most can learn to self-manage as long as data are available to them (e.g. PatientView). Daily activities may be symptom-limited and some occupations are unsuitable (e.g. active armed forces, pilot).

    Complications

    Hypertension, proteinuria, FSGS, CKD. These require specialist investigation.

  • Genetic Testing

    CLCNKB testing (UKGTN-approved) with or without SLC12A3 testing,  can be requested by consultants, via forms available here

    Genetic counseling

    Since T3BS is a recessive trait, the recurrence risk for parents with an affected child is 25%. If parents already have other children who are not obviously affected, this does not exclude T3BS because clinical symptoms can appear later in life. If the mutations in their affected child are known, specific DNA testing of other child(ren) may be performed. Adults with T3BS have a low risk of having children with GS (~1 in 400) unless patient and his/her partner are consanguineous.

    Prenatal diagnosis

    Although technically feasible, antenatal diagnosis for T3BS is not usually offered because of the good prognosis in the majority of cases.

Bartter Syndrome Type 3 Clinician Information Version 6 Updated April 2017
Written by the Hypokalaemic Alkaloses Rare Disease Group