Renal Sodium Handling Study in an Atypical Case of Bartter's Syndrome Associated with Mitochondriopathy and Sensorineural Blindness

Abstract

Bartter's syndrome is a disorder that has been linked to mutations in one of three ion transporter proteins: NKCC2 (type I), ROMK (type II) and CCLNKB (type III), which affects a final common pathway that participates in ion transport by thick ascending limb cells. We present an atypical case of mitochondriopathy combined with tubule functional disturbances compatible with Bartter's syndrome and definitive sensorineural blindness. Our patient had a peculiar clinical presentation with signs of salt and volume depletion, low blood pressure and secondary hyperaldosteronism, associated with hypokalemic metabolic alkalosis, hypocalcemia and severe hypomagnesemia, uncommon in genetic forms of Bartter's syndrome. The enhanced absolute and fractional sodium excretion in our patient compared to volunteers was accompanied by increased post-proximal sodium rejection, suggesting a striking ion transport dysfunction in these nephron segments. These findings lead to the Bartter's syndrome diagnosis, accompanied by a suppose mitochondrial tick ascending loop of Henle epithelium dysfunction that may reflect the high energy supplied by mitochondria electron transport chain, required for this nephron segment to maintain normal ion transport.

Renal manifestations of primary mitochondrial disorders

“…Notably, no other organs were affected in these four patients; thus, kidney disease was the initial manifestation and dominant feature of the MID and, therefore, the phenotype was not consistent with MELAS syndrome at the time of diagnosis (63). In a patient with sensorineural blindness, attributed to a non-genetically proven MID, Bartter-like syndrome was the second phenotypic feature (64). In a consanguineous family with isolated COX-deficiency due to a mutation in the COX10 gene, which encodes the heme A:farnesyltransferase, increased urinary amino acids suggested proximal renal tubulopathy (65).…”

Severe Hypokalemic Paralysis as a Manifestation of a Mitochondrial Disorder

“…Further arguments for a non-syndromic MtD are that hypokalemia or hyperaldosteronism has been previously reported as clinical manifestations of MtD (Goto et al 1990;Harvey and Barnett 1992;Wang et al 2000;Menegon et al 2004;Park et al 2004;Emma et al 2006). Emma et al (2006) reported a 14-year-old patient with KSS who developed Bartter's syndrome (hyper-reninemic hyperaldosteronism).…”

“…Hyper aldosteronism was reported as one among various other phenotypic features in a single male with KSS (Mihai et al 2009). Menegon et al (2004) described a patient with atypical Bartter's syndrome and MtD who presented with salt and volume depletion, hypotonia, and secondary hyperaldosteronism associated with hypokalemic metabolic alkalosis, hypocalcaemia and severe hypomagnaesemia. These abnormalities were attributed to mitochondrial dysfunction within the epithelium of the ascending loop of Henle (Menegon et al 2004).…”

“…Menegon et al (2004) described a patient with atypical Bartter's syndrome and MtD who presented with salt and volume depletion, hypotonia, and secondary hyperaldosteronism associated with hypokalemic metabolic alkalosis, hypocalcaemia and severe hypomagnaesemia. These abnormalities were attributed to mitochondrial dysfunction within the epithelium of the ascending loop of Henle (Menegon et al 2004). In a 9-year-old male patient, hypokalemia and hypophosphatemia triggered severe proximal muscle weakness from mitochondrial myopathy (Wang et al 2000).…”

“…Hypertelorism and brachydactylia were reported as physical traits of MtD (Pronicki et al 2002;Finsterer 2011). Furthermore, hypokalemia has been occasionally described as a manifestation of a syndromic, multisystem MtD (Wang et al 2000;Menegon et al 2004;Emma et al 2006), particularly in Kearns-Sayre syndrome (KSS) (Goto et al 1990;Harvey and Barnett 1992;Park et al 2004;Emma et al 2006). However, severe hypokalemia resulting in muscle weakness and rhabdomyolysis has not been reported as a phenotypic feature of a non-syndromic MtD.…”