Table 3 In- and exclusion criteria BUDDI trial

1. Inclusion in BAMBI, BASCET or BATSCH trial;

2. Written informed consent

Or

1. Males or females aged ≥7 years to ≤17 years;

2. One of the following:

3. Above clinical cut-off scores of altered sensory reactivity on the Sensory Profile and either a clinical ASD or ADHD diagnosis based on DSM-5 (or DSM-IV) or an epilepsy diagnosis,

4. Criteria met for autism on DSM-IV or V and Social Responsiveness Scale (SRS-2)

5. A history of behavioral problems combined with a definite diagnosis of TSC: either meeting criteria for clinical definite TSC, or a mutation identified in the TSC1 or TSC2 gene;

6. Written informed consent

1. Inability to comply with the protocol-specified procedures for the duration of the study, including treatment, blood sampling to control diuretic effects;

a. This does not include inability to perform neurocognitive testing due to intellectual disability, as there is no minim IQ needed.

2. Presence of a severe medical or genetic disorder other than related to ASD, TSC or epilepsy;

3. Serious, unstable illnesses including, gastroenterological, respiratory, cardiovascular (arrhythmias, QT interval lengthening), endocrinologic, immunologic, hematologic disease, dehydration or hypotension, electrolyte disturbances (Na < 133 mmol/L, K < 3.5 mmol/L or Ca < 2.17 mmol/L (<13y) or < 2.2 mmol/L (>13y);

4. Renal insufficiency (CKD st2–5; estimated glomerular filtration rate < 90 ml/min/1.73 m2), congenital or acquired renal disease with decreased concentration capacity (tubulopathy, diabetes insipidus) and liver insufficiency interfering with excretion or metabolism of bumetanide;

5. Start of behavioral treatment during study;

6. Treatment with psychoactive medications, including antipsychotics and AEDs, except methylphenidate, is allowed if on a stable regime in terms of types and dosage from 2 months prior to the study to the end of the study;

7. Treatment with NSAIDS, aminoglycosides, digitalis, antihypertensive agents, indomethacin, probenecid, acetazolamide, Lithium, other diuretics (e.g., furosemide, hydrochlorothiazide), drugs known to have a nephrotoxic potential;

8. Documented history of hypersensitivity reaction to sulfonamide derivatives;

9. Body weight < 30 kg (for reason of dosing).