A CASE OF ADULT ONSET BARTTER’S SYNDROME DEPARTMENT OF NEPHROLOGY GOVT.RAJAJI HOSPITAL, MADURAI MEDICAL COLLEGE

25 year old male who is a known smoker, alcoholic, admitted with sudden onset weakness of both legs for 1 day. Patient was apparently normal one day before admission, he had sudden onset symmetric weakness of both lower limb which progressed to involve both upper limb. H/o difficulty in using both upper and lower limb H/o difficulty in raising hand above head and mixing food H/o difficulty to stand from squatting position and holding slippers H/o strenuous exercise the day before weakness No H/o of difficulty in lifting head from pillow

No H/o involuntary micturition or defecation No H/o fever / seizure / altered sensorium No H/o blurring of vision /difficulty in opening eyes No H/o breathing difficulties No H/o suggestive of sensory system/ autonomic system involvement No H/o vomiting / diarrhoea No H/o palpitation / tremor No H/o animal bite

PAST HISTORY: Patient had similar episode in past- 1ST episode 6 months back and 2ND episode 3 months back- for which he got treated in local GH. Further evaluation was not done. Treatment records were not available. FAMILY HISTORY: No other family member had similar complaints. Patient was born to non consanguineous marriage DRUG HISTORY: No H/o suggestive of intake of any diuretics, insulin, antibiotics

GENERAL EXAMINATION: Conscious Oriented No pallor / cyanosis / clubbing Not icteric No pedal edema / lymphadenopathy

VITALS; BLOOD PRESSURE- 110/70 mmHg PULSE RATE- 94/MIN RESPIRATORY RATE-20/MIN Single breath count-26

Systemic examination: CNS Higher function examination- normal Cranial nerve examination- normal Spinomotor system examination: R L BULK NORMAL NORMAL TONE U/L HYPOTONIA HYPOTONIA L/L HYPOTONIA HYPOTONIA

R L POWER U/L 1/5 1/5 L/L 1/5 1/5 HAND GRIP 50% 50% NO NECK MUSCLE WEAKNESS REFLEXES: SUPERFICIAL REFLEX PRESENT PRESENT

PLANTAR REFLEX DEEP TENDON REFLEX RIGHT LEFT BICEPS 1+ TRICEPS SUPINATOR KNEE ANKLE PLANTAR REFLEX FLEXOR

SENSORY SYSTEM EXAMINATION- NORMAL CEREBELLAR SYSTEM EXAMINATION- NO NYSTAGMUS/ DYSARTHRIA COORDINATION COULD NOT BE TESTED SPINE AND CRANIUM EXAMINATION- NORMAL NO SIGNS OF MENINGEAL IRRITATION

CVS- S1S2+ NO MURMUR RS- B/L AIR ENTRY NO ADDED SOUND ABDOMEN- SOFT NO ORGANOMEGALY

Recurrent Quadriplegia Plantar flexor No neck muscle weakness Normal BP H/O strenuous exercise sensory system normal Normal bladder sensation

INVESTIGTION RBS-100mg/dl UREA-42mg/dl CREATININE-0.8 mg/dl TC-5200 cells/cumm DC- N60/L31/M9 HB- 14.3 g% PCV-36%

ECG- 100/min, normal axis, U wave SODIUM - POTASSIUM - (mmol/L) URINE K+- 24.20 mEq/L (SPOT) 11/04 16/04 27/04 30/04 146 140 142 143 1.7 3.89 2.49 2.77

URINE PH- 6.5 URINE OSMOLALITY- 223 mosm/kgH2O SERUM OSMOLALITY- 303 mosm/kgH2O TTKG= Urine k+/serum K+ divided by urine osmolality/serum osmolality TTKG-5.33

SERUM MAGNESIUM- 2.O mg/dl URINE CHLORIDE-111 mmol/L URINE SODIUM- 45 mEq/L URINE CALCIUM- 6.80 mg/dl URINE CREATININE- 21.86 mg/dl URINE Ca/Cr RATIO-0.311

ABG CT ABDOMEN- Normal study USG- normal study PH 7.46 HCO3 25.4 PCO2 37.3 Na+ 146 K+ 2.84 CT ABDOMEN- Normal study USG- normal study TFT – normal (TSH-1.2 microIU/L)

Flaccid acute quadriplegia Normal BP Hypokalemia TTKG-5 Flaccid acute quadriplegia Normal BP Hypokalemia TTKG-5.33 (renal loss of potassium) URINE Ca/Cr RATIO-0.311 (hypercalciuria) Normal serum magnesium Metabolic alkalosis

Clinical findings and lab investigations points towards ADULT ONSET- BARTTER’S SYNDROME. Patient was treated with syrup kcl. Patient’s power improved and was discharged.

PSEUDO HYPOKALEMIA RULED OUT URINE K+ 24.20 mg/dl TTKG 5.33 BLOOD PRESSURE NORMAL ACID BASE STATUS METABOLIC ALKALOSIS

URINE Cl- 111 mmol/L URINE Ca/Cr 0.311 BARTTER’S SYNDROME

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BARTTER’S SYNDROME Autosomal recessive Prevalence is 1 in 1 million Salt losing tubulopathy of frusemide type Affects thick ascending loop of henle BP is normal due to salt wasting and renal release of prostacyclin, prostaglandin E2. Hypercalciuria due loss of lumen positive voltage gradient- necessary for paracellular absorbtion of calcium

Abnormal proteins involved are Type 1- NKCC2 COTRANSPORTER Type2- ROMK CHANNEL Type3- CLC-Kb CHANNEL Type4- BARTTIN Type5- CaSR

TYPE 3 (CLASSICAL BARTTER’S SYNDROME) TYPE 1 AND 2 (ANTENATAL-NEONATAL BARTTER AND HYPERPROSTAGLANDIN E SYNDROME) Most severe form Maternal polyhydramnios, premature birth, severe dehydration, failure to thrive and growth retardation. Nephrocalcinosis occurs TYPE 3 (CLASSICAL BARTTER’S SYNDROME) Manifest later in childhood or adolescent age group Muscle weakness, cramps, fatigue, constipation Nephrocalcinosis doesnot occur

TYPE 5 (HYPOCALCEMIA WITH BARTTER’S SYNDROME) TYPE 4 (ANTENATAL BARTTER’S SYNDROME WITH DEAFNESS) Affects gene, BARTTIN, which regulates chloride channels ClC-Ka and ClC-Kb; both are also present in inner ear TYPE 5 (HYPOCALCEMIA WITH BARTTER’S SYNDROME) Associated with hypoparathyroidism Due to gain of function mutation of CaSR

In the kidney, loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 (OAT1) and exert their diuretic action by binding to the Na-K-2Cl cotransporter type 2 (NKCC2) in the thick ascending limb and the Na-Cl cotransporter (NCC) in the distal convoluted tubule, respectively. Downstream from the primary site of diuretic action, an increase in epithelial Na+ channel (ENaC) abundance is induced by chronic furosemide or hydrochlorothiazide treatment.so there is increased Na+ absorption in distal tubular segments. The abundance of NKCC2 and NCC is increased by furosemide and hydrochlorothiazide, respectively. This compensatory upregulation suggests that either diuretic may activate the ion transporter within the primary site of action. In the proximal tubule, the abundance of OAT1 is increased by chronic treatment with furosemide or hydrochlorothiazide.