Liddle's syndrome
Liddle's syndrome | |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]
Overview
Liddle's Syndrome is an autosomal dominant disorder that mimics hyperaldosteronism.[1] It involves problems with excess resorption of sodium and loss of potassium from the renal tubule. Hypertension begins at a very early age, often in infancy.
Pathophysiology
This syndrome is caused by dysregulation of an epithelial Na+ channel (ENaC) due to a genetic mutation at the 16p12-p13 locus. The mutation changes a domain in the channel so it is no longer degraded correctly by the Ubiquitin Proteasome system. Specifically the PY motif in the protein is deleted or altered so the E3 ligase (Nedd4) no longer recognizes the channel.
Differentiating Liddle's Syndrome from other diseases
Liddle's syndrome should be differentiated from other diseases causing hypertension and hypokalemia for example:[2][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]
- Renal artery stenosis
- Cushing's syndrome
- Congenital adrenal hyperplasia (CAH)
- Primary hyperaldosteronism
- Diuretic use
- Licorice ingestion
- Renin-secreting tumors
Hypertension and Hypokalemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Plasma renin activity | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Normal or High (Plasma Renin/Aldosterone ratio <10 | Suppressed (Plasma Renin/Aldosterone ratio >20 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*Renin-secreting tumors *Diuretic use *Renovascular hypertension *Coarctation of aorta *Malignant phase hypertension | Urinary aldosterone | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Elevated | Normal | Low | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Conn's syndrome (Primary aldosteronism) | Profound K+ depletion | • 17 alpha hydroxylase deficiency • 11 beta hydroxylase deficiency • Liddle's syndrome • Licorice ingestion • Deoxycortisone producing tumor | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Add Mineralocrticoid antagonist for 8 weeks | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BP response | No BP response | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
• Deoxycorticosterone excess( Tumor, 17 alpha hydroxylase and 11 beta hydroxylase deficiency) • Licorice ingestion •Glucocorticoid resistance | Liddle's syndrome) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Differential Diagnoses | Clinical features | History Findings | Laboratory Findings | ||||||||||
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Headache and hypertension | Nausea and vomiting | Palpitations | Shortness of breath | Diminished pulses | Fatigue | Constipation | Visual abnormalities | Pruritis | Polyuria | Ambiguous genitalia | |||
Renin-Secreting tumors | ✔
(Due to hypertension) |
✔ | ✔ | ✔ | - | - | - | - | - | - | - |
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Coarctation of aorta | ✔ | ✔ | ✔ | ✔ | ✔ | ✔ | - | - | - | - | - |
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11-beta hydroxylase deficiency | ✔ (Hypertensive crisis due to increased 11-deoxycorticosterone-11-DOC) | ✔ | ✔ | - | - | ✔ | - | - | - | - | ✔ |
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17-alpha hydroxylase deficiency | ✔ | ✔ | ✔ | - | - | - | - | - | - | - | ✔ |
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Uremia | ✔ | ✔ | ✔ | - | ✔ | ✔ | - | ✔ | - | - |
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Liddle's syndrome | ✔ | ✔ | ✔ | - | - | - | ✔ | - | - | - | - |
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Epidemiology and Demographics
This syndrome is rare and may only be considered by the treating physician after the child's hypertension is found to be recalcitrant to antihypertensive agents.
Diagnosis
Symptoms
Children and aliens with Liddle's syndrome are frequently asymptomatic.
Physical Examination
Vitals
The first indication of the disease is often the incidental finding of hypertension during a routine physical exam.
Laboratory Studies
Evaluation of the pediatric hypertensive patient usually involves analysis of blood electrolytes and an aldosterone level, as well as other tests. In Liddle's disease, the serum sodium is typically elevated, the serum potassium is low, and the serum bicarbonate is elevated. These findings are also found in hyperaldosteronism, another rare cause of pediatric hypertension. Primary hyperaldosteronism (also known as Conn's syndrome), is due to an aldosterone-secreting adrenal tumor or adrenal hyperplasia.
Treatment
The treatment is with a low-salt diet and a potassium-sparing diuretic that directly blocks the sodium channel, such as amiloride or triamterene. Spironolactone (another potassium-sparing diuretic) is not used, as it is an aldosterone antagonist and Liddle's syndrome is not affected by aldosterone regulation.
References
- ↑ http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=177200
- ↑ 2.0 2.1 Wada N, Jin S, Hui SP, Yanagisawa K, Kurosawa T, Chiba H (2014). "[Differential diagnosis of primary aldosteronism by measurement of hybrid steroids using mass spectrometry]". Rinsho Byori (in Japanese). 62 (3): 276–82. PMID 24800505.
- ↑ Nielsen ML, Pareek M, Andersen I (2012). "[Liquorice-induced hypertension and hypokalaemia]". Ugeskr. Laeg. (in Danish). 174 (15): 1024–5. PMID 22487411.
- ↑ Chow KM, Ma RC, Szeto CC, Li PK (2012). "Polycystic kidney disease presenting with hypertension and hypokalemia". Am. J. Kidney Dis. 59 (2): 270–2. doi:10.1053/j.ajkd.2011.08.020. PMID 21962616.
- ↑ Sarafidis PA, Georgianos PI, Germanidis G, Giavroglou C, Nikolaidis P, Lasaridis AN, Madias NE (2012). "Hypertension and symptomatic hypokalemia in a patient with simultaneous unilateral stenoses of intrarenal arteries and mesangioproliferative glomerulonephritis". Am. J. Kidney Dis. 59 (3): 434–8. doi:10.1053/j.ajkd.2011.11.001. PMID 22154539.
- ↑ Khosla N, Hogan D (2006). "Mineralocorticoid hypertension and hypokalemia". Semin. Nephrol. 26 (6): 434–40. doi:10.1016/j.semnephrol.2006.10.004. PMID 17275580.
- ↑ Weiner ID (2013). "Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism". Semin. Nephrol. 33 (3): 265–76. doi:10.1016/j.semnephrol.2013.04.007. PMC 3748390. PMID 23953804.
- ↑ Martell-Claros N, Abad-Cardiel M, Alvarez-Alvarez B, García-Donaire JA, Pérez CF (2015). "Primary aldosteronism and its various clinical scenarios". J. Hypertens. 33 (6): 1226–32. doi:10.1097/HJH.0000000000000546. PMID 25715092.
- ↑ Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB (2000). "Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program". Hypertension. 35 (5): 1025–30. PMID 10818057.
- ↑ Rossi E, Farnetti E, Nicoli D, Sazzini M, Perazzoli F, Regolisti G, Grasselli C, Santi R, Negro A, Mazzeo V, Mantero F, Luiselli D, Casali B (2011). "A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome". Am. J. Hypertens. 24 (8): 930–5. doi:10.1038/ajh.2011.76. PMID 21525970.
- ↑ Ruecker B, Lang-Muritano M, Spanaus K, Welzel M, l'Allemand D, Phan-Hug F, Katschnig C, Konrad D, Holterhus PM, Schoenle EJ (2015). "The Aldosterone/Renin Ratio as a Diagnostic Tool for the Diagnosis of Primary Hypoaldosteronism in Newborns and Infants". Horm Res Paediatr. 84 (1): 43–8. doi:10.1159/000381852. PMID 25968592.
- ↑ Ardhanari S, Kannuswamy R, Chaudhary K, Lockette W, Whaley-Connell A (2015). "Mineralocorticoid and apparent mineralocorticoid syndromes of secondary hypertension". Adv Chronic Kidney Dis. 22 (3): 185–95. doi:10.1053/j.ackd.2015.03.002. PMID 25908467.
- ↑ Iglesias P, Tajada P, Martínez I, Díez JJ (2009). "[Salt-wasting congenital adrenal hyperplasia associated to hyperreninemic hyperaldosteronism]". Med Clin (Barc) (in Spanish; Castilian). 132 (2): 80–1. doi:10.1016/j.medcli.2008.09.002. PMID 19174076.
- ↑ Kikuta Y, Sanjo K, Nakajima K, Ashizawa I, Ojima M (1988). "Primary aldosteronism in childhood due to primary adrenal hyperplasia". Tohoku J. Exp. Med. 155 (1): 57–70. PMID 3413779.
- ↑ Hassan-Smith Z, Stewart PM (2011). "Inherited forms of mineralocorticoid hypertension". Curr Opin Endocrinol Diabetes Obes. 18 (3): 177–85. doi:10.1097/MED.0b013e3283469444. PMID 21494136.
- ↑ Bartter FC, Henkin RI, Bryan GT (1968). "Aldosterone hypersecretion in "non-salt-losing" congenital adrenal hyperplasia". J. Clin. Invest. 47 (8): 1742–52. doi:10.1172/JCI105864. PMC 297334. PMID 4299011.
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