Severe renal tubulopathy in a newborn due to BCS1L gene mutation: effects of different treatment modalities on the clinical course

Gene. 2013 Oct 10;528(2):364-6. doi: 10.1016/j.gene.2013.07.007. Epub 2013 Jul 26.


Very early onset Toni-Debré-Fanconi Syndrome, a disorder of proximal renal tubules of the kidney which results in the increased urinary excretion of glucose, amino acids, uric acid, phosphate and bicarbonate, could be the manifestation of various inborn errors. Defects of oxidative phosphorylation are a heterogeneous group of disorders with various clinical presentations. Recently, patients with early liver failure, renal tubulopathy and encephalopathy due to the mutations in the BCS1L gene coding for a structural protein in mitochondrial complex III have been described. Ten-day-old female newborn was referred to our clinic because of intractable acidosis. Physical examination revealed severe hypotonia, and hepatomegaly. The laboratory examinations revealed lactic acidosis, increased blood alanine, alanine aminotransferase and aspartate aminotransferase levels, generalized aminoaciduria and glucosuria. The tubular reabsorption of phosphate was reduced. Because of multisystem involvement, mitochondrial disease was suspected and the mutational analysis of the BCS1L gene revealed homozygous P99L mutation. As the patient was unresponsive to bicarbonate replacement, oral dichloroacetate and peritoneal dialysis, continuous high dose intravenous sodium bicarbonate therapy with a dose up to 1.25 mEq/kg/h was started. The patient got on well until the age of 9 months when she died of sepsis. It was stressed that high dose intravenous continuous sodium bicarbonate therapy could be an alternative treatment option in patients with severe acidosis and renal tubulopathy resistant to dichloroacetate and peritoneal dialysis. Patients with BCS1L mutations should be considered in the differential diagnosis of severe tubulopathy in the newborn period.

Keywords: BCS1L; BCS1L gene; DCA; GRACILE syndrome; Growth retardation-aminoaciduria-cholestasis-iron overload-lactic acidosis-early death syndrome; Lactic acidosis; Mitochondrial disease; Renal tubulopathy; dichloroacetate.

Publication types

  • Case Reports

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Consanguinity
  • Electron Transport Complex III / genetics*
  • Fanconi Syndrome / diagnosis*
  • Fanconi Syndrome / genetics
  • Fanconi Syndrome / therapy
  • Fatal Outcome
  • Female
  • Humans
  • Infant, Newborn
  • Pseudomonas Infections / diagnosis
  • Sepsis / diagnosis


  • BCS1L protein, human
  • ATPases Associated with Diverse Cellular Activities
  • Electron Transport Complex III