A Case of Bartter's Syndrome

DR.G.BALAJI PROF.DR.G.SUNDARAMURTHY’S unit- M6

40 year male presented with weakness of both lower limbs of 4 hours duration.
Sudden onset, involving both lower limbs simultaneously.
He feels the limbs are lifeless.
No h/o involvement of upper limbs, trunk muscles, neck muscles.
No h/o any sensory disturbances.
No bowel or bladder disturbances.

No h/o trauma, back pain, fever , myalgia.
No h/o diarrhoea, vomiting, abdominal pain.
No h/o dysuria, hematuria, oliguria.
No h/o headache , blurring of vision, syncope attacks, seizures
no h/o chest pain cough, dyspnea, palpitations, hemoptysis.
No h/o any heavy meals.,exercise

Past history:
Not a case of DM, SHT, IHD, PT, Bronchial asthma.
No h/o drug intake , fever, diarrhoea.
No similar episodes in the past.
Left upper limb amputated above elbow following a trauma.
Personal history:
Alcohol consumer. last consumption 5 days ago.
No h/o smoking, drug addiction, extra marital , or premarital affairs.

Acute paraparesis
Guillain- Barre syndrome
Cns-
para sagittal meningiomas
Anterior cerebral artery ischemia
Superior sagittal or cortical venous thrombosis
Acute hydrocephalus
Spinal cord
Intra spinal lesion in mid thoracic level

Spinal lesions-
Compressive lesions- ivdp, tumour abscess or hematoma, malignancy.
Vascular- spinal cord infarction, av fistula,
Transverse myelitis.
( no sensory loss or upper level of lesions.)

Cauda equina lesions:
Trauma, mid line disc herniation, intra spinal tumour- sphincter is affected.
Anterior horn cell disease- polio
Guillain- Barre syndrome
Myopathy.
Periodic paralysis

examination
Pt conscious, oriented, afebrile
Obeys commands.
Not dyspneic or tachypneic.
No Icterus/ cyanosis/ clubbing/ pedal edema/ lymph node enlargement.
Pulse: 80/ min regular, normal volume and character. All peripheral pulses felt equally in all 4 limbs.
BP: 110/70 mm Hg in RUL.
RR: 14 /min , abdomino thoracic.

CVS: S1, S2 heard. No murmurs.
RS: NVBS. No added sounds
P/A: soft non tender,
No organomegaly, no free fluid.
No mass.

Central nervous system
Higher functions :
Pt is conscious, oriented to time, place and person.
Speech intact.
Memory normal.
CRANIAL NERVES :
Normal.

Motor system
upper limb right left- amputated
Bulk normal
Tone normal
Power 4/5
Reflexes:
DTR biceps +
triceps +
supinator +
Superficial abdominal +

Lower limbs right left
Bulk normal normal
Tone reduced reduced
Power 1/5 1/5
Reflexes
knee absent absent
Ankle absent absent
Plantar no response no response

No axial muscle weakness
SENSORY SYSTEM
Touch,Pain , temperature : present
Vibration, joint position: present.
Cortical sensation: intact.
Spinal vibration: present

Cerebellum ;
Upper limbs: no cerebellar signs
Lower limbs; could not be examined.
GAIT:
Could not be examined.
Skull and spine – NORMAL.
SPINAL VIBRATION – present at all levels

Problems
(Apparent) paraparesis of sudden onset- hours
Areflexia in lower limbs
Bowel and bladder : not involved
Sensations- intact.
No spinal tenderness.
No signs of increased ICT.

AIDP- Guillain Barre syndrome
Channelopathies- Hypokalemic periodic paralysis

Investigations
CBC:
Hb- 14.5 g
TC- 5400
DC: P- 64, L-36
ESR- 6/12
PCV: 42%
Platelets- 1.5 lakhs.
RFT:
UREA- 26 mg
Creatinine- 1.1 mg

Urine routine-
Albumin- nil
Sugar- nil,
deposits- nil
Pus cells- nil
Chest X-RAY: normal
ECG - flat P wave, U wave, prolonged QT interval.

ELECTROLYTES:
Sodium: 137 meq/l
Potassium- 1.3 meq/l
Chloride- 88 meq/l
Bicarbonate- 33 meq/l

diagnosis
Hypokalemia -?cause

Treatment
IV Potassium- 20 meq of KCl.
Oral KCl- 25 ml/ hr.
Patient regained power in lower limbs.
Reflexes returned.
Pt was able to walk.

HYPOKALEMIA:
REDUCED INTAKE
RENAL WASTING - most common cause
TRANS CELLULAR SHIFT.

Hypokalemia
plasma K+ concentration <3.5 mmol/L,
CAUSES:
I. Decreased intake ( Seldom a sole cause for K+ depletion)
A. Starvation
B. Clay ingestion (Geophagia – binds dietary K+ and Fe)

II. Redistribution into cells
A. Acid-base
1. Metabolic alkalosis ( 1.K+ redistribution into cell 2.Excess renal loss)
B. Hormonal
1. Insulin (Stimulation of Na H antiporter and secondary activation of NA K ATP ase pump)
2. beta-Adrenergic agonists (1.Directly induces cellular uptake of K+ 2.Stimulates insulin secretion)
3. alpha-Adrenergic antagonists

C. Anabolic state (D/T K+ shift into newly formed cells)
1. Vitamin B12 or folic acid ( RBC production)
2. Granulocyte-macrophage colony stimulating factor (white blood cell production)
3. Total parenteral nutrition

D. Other
1. Pseudo hypokalemia
2. Hypothermia
3. Hypokalemic periodic paralysis (Calcium Channelopathy)
4. Barium toxicity

pseudohypokalemia
Prevented storing the blood sample on ice or rapidly separating the plasma from the cells.
e.g., acute myeloid leukemia
…..low measured plasma K+ concentration d/t white blood cell uptake of K+ at room temperature

III. Increased loss
A. Non renal
1. Gastrointestinal loss (1.diarrhea – per se loss of K+)…profuse diarrhea, villous adenomas, VIP oma, laxative abuse 2.Vomitting - mainly d/t ^ renal K+ excretion caused by volume depletion and metabolic alkalosis)
2. Integumentary loss (sweat ) (ECF contraction…Aldosterone secretion )

B. Renal
1.Increased distal flow :
diuretics
osmotic diuresis
salt-wasting nephropathies

2. Increased secretion of potassium
I. Mineralocorticoid excess:
Primary hyperaldosteronism (ca, Conn's , hyperplasia)… low plasma renin activity
Secondary hyperaldosteronism (1.malignant hypertension, 2.renin-secreting tumors –RCC, Ovarian Ca, Wilm’s tumor, 3.renal artery stenosis, 4.hypovolemia)… Hyperreninemia
Bartter's s .. (Na K 2 Cl pump mutation…Volume depletion…hyperaldosteronism…K+ secreted

Apparent Mineralocorticoid excess (licorice, chewing tobacco, carbenoxolone) …cortisol occupies the aldosterone receptor for action…cortisol to cortisone does not occur d/t 11 beta HSDH deficiency/inhibition …– low renin and aldosterone
Congenital adrenal hyperplasia ( D/T non aldosterone Mineralocorticoids – corticosterone, deoxycorticosterone)
Cushing's s .. (cortisol formed overwhelms the activity of 11 beta HSDH)

II. Distal delivery of non-reabsorbed anions:
vomiting …HCO3 in urine
nasogastric suction
proximal (type 2) renal tubular acidosis
diabetic ketoacidosis …Beta OH butyrate
glue-sniffing (toluene abuse) …Hippurate
penicillin derivatives …(1.Secrete K+; 2. Osmotic diuresis)

III. Other:
Amphotericin B …( ^ distal nephron K+ permeability)
Liddle's syndrome … (ENaC up regulation in CCD…negative Electrical gradient in lumen…H+ & K+ secretion)
Hypomagnesaemia …(Resistant to treatment)

Genetic disorders
Hypokalemic periodic paralysis
Bartter's syndrome
Gitelman's syndrome
Liddle's syndrome
Apparent mineralocorticoid excess
Glucocorticoid-remediable hyperaldosteronism

APPROACH TO HYPOKALEMIA HYPOKALEMIA urine potassium < 25 mEq/day urine potassium >30 mEq/day

Urinary conservation +

Urinary conservation -

Lab values
Sodium-134 meq
Potassium- 1.46 meq
Chloride- 84.3 meq
Bicarbonate- 33.2 meq
Serum calcium- 9.3 meq
Magnesium- 2.0 mg
Urine specific gravity- 1.030

USG ABDOMEN-
normal sized kidneys.
CMD Present.
Normal echoes.
X- RAY KUB
No evidence of any calculus.

ABG 1 st day 2 nd day PH 7.52 7.48 HCO3 32.6 36.6 PCO2 40.5 50.1 PO2 80.4 74 ANION GAP 13.5 10.3 SO2 97 95.4

THYROID:
T3 -125.82
T4-9.68
TSH-1.472.
ENT opinion- normal .
No hearing loss.
LFT:
Serum proteins- 6.3 gms
Albumin- 4.3 gms
Globulins-2.0 gms

24 HR urine excretion-
sodium- 322meq (100-260)
Potassium-144 meq (25-100)
Chloride- 516.6 meq ( 110-250)
Calcium-418.6 mgm (<300 mg/day)

Hypokalemia- 1.4 meq
Metabolic alkalosis : ph- 7.54
Normal calcium- 9.3 meq
Normal magnesium- 2.o meq
Normal blood pressure- 110/70 mm HG.
URINE chloride-516 meq
Urine potassium-144 meq

Final diagnosis
Bartter’s syndrome-
Type- 111

BARTTER’S SYNDROME
Autosomal recessive
Fn of thick ascending LOH affected
Inactivating mutations of one of 4 genes encoding membrane proteins (Types I to IV)
Gain of function mutation in extracellular Ca ion sensing receptor (CaSR)… variant of Bartter presenting with Hypocalcemia (AD inheritance)

Bartter’s syndrome types
Type I : mutation in the gene for Na K 2Cl cotrasporter (NKCC2) + on the apical membrane of LOH
Type II : mutation in the gene for ATP regulated K channel (ROMK)
Type III : mutation in the basolateral voltage gated Cl channel (ClC – Kb)
Type IV : mutation in the BSND protein (barttin) that activates beta subunit for ClC Kb and ClC Ka . Associated with deafness

Type V : Gain of function mutation in the CaSR gene … + with Hypocalcemia
…. First four types are autosomal recessive : type V is autosomal dominant

Clinical features
Present in antenatal period
or in neonates( III can + in early childhood)
Antenatal …
Polyhydramnios & Preterm labour
Postnatal …
Polyuria , Polydipsia ,Growth retardation , Dehydration , Nephrocalcinosis (universal in I & II ; only in 20% of III) , Muscle weakness , Fatigue

Systemic features include fever, vomiting, diarrhea +…
Probably all are d/t PG mediation
fever can be d/t dehydration
vomiting d/t hypokalemic paralytic ileus.
TYPE IV : Sensorineural deafness specific detected as early as 1 month of age : also CRF progression in childhood is common

Biochemical abnormalities
Hypokalemic metabolic alkalosis
Hyperreninemic hyperaldosteronism
Normal blood pressure
Inappropriate urine excretion of K +
Inappropriate urine excretion of Cl –
Hypercalciuria
Normo magnesemia
Urinary PG ^ed in majority
Blunted response to loop diuretics

Nephrocalcinosis + + +- + + - Polyhydramnios + + + + - - FTT + + + + - - Growth Retardation + + + + - - Polyuria + + + + + - Polydipsia + + + + + - Muscle cramps/pain - - - - + +- Chondrocalcinosis - - - - - +- SN hearing loss - - - + - - Hypocalcemia - - - - + - FEATURES B I B II B III B IV B V GM

Treatment
Restore plasma K to about 3.5 mmol/l
K+ supplementation / Spironolactone / Amiloride
PG inhibitor like indomethacin 2 mg/day in divided doses …in infants have reduced incidence of growth retardation

Differential diagnosis
1.Gitelman’s syndrome
( Differentiated by Hypocalciuria + : Hypomagnesaemia +)
2.Vomiting
(Differentiated by Urinary Cl < 20 meq/L)
3.Abuse of loop diuretics
(H/O drug intake + or assaying the expected drugs in urine)
…. All are observed in older patients

American journal of medicine : vol 61: issue 1 :1985
A patient with Bartter's syndrome in whom the disease was recognized at 52 years of age has been described in….

Adult onset Bartter diagnosed at the age of 40 yrs
Korean journal of medicine : vol 10 : number 4 :1995

Male who had not been diagnosed as Bartter syndrome type IV until 28 yr because of a mild clinical manifestation. The patient also had congenital deafness .
The Journal of Clinical Endocrinology & Metabolism : Vol. 88 : Number 2 : 2003

Deaf daughter of consanguineous parents, who was referred for the first time at the age of 20 , because of refractory hypocalcaemia
Antenatal polyhydramnios +
Polydipsia and polyuria. The patient's height and weight reached, respectively, 165 cm and 70 kg
Oxford journal of medicine : vol 22 : number 1 : 2006

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A Case of Bartter's Syndrome

by Stanley Medical College, Department of Medicine on Aug 21, 2011

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