Neuropediatrics 2017; 48(02): 108-110
DOI: 10.1055/s-0036-1593984
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Severe Metabolic Acidosis and Hepatopathy due to Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate

Elizabeth A. Sellars
1   Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Tonya Balmakund
2   Division of Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Katherine Bosanko
1   Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Brandi L. Nichols
3   Department of Clinical Nutrition, Arkansas Children's Hospital, Little Rock, Arkansas, United States
,
Stephen G. Kahler
1   Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
,
Yuri A. Zarate
1   Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
› Author Affiliations
Further Information

Publication History

22 July 2016

26 September 2016

Publication Date:
22 November 2016 (online)

Abstract

Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a recently described autosomal recessive mitochondrial disease characterized by early onset of neurological symptoms, a biphasic clinical course, and distinctive neuroimaging. Pathogenic variants in the EARS2 gene that encode for mitochondrial glutamyl-tRNA synthetase are responsible for LTBL. Here, we describe the clinical course of an infant diagnosed with an acute crisis of LTBL and severe liver disease. This article illustrates the utility of blood lactate quantification in addition to basic metabolic testing and brain imaging in a child with low tone and poor growth. In addition, this case demonstrates the utility of current genetic diagnostic testing, in lieu of more invasive procedures, in obtaining rapid answers in this very complicated group of disorders.

 
  • References

  • 1 Steenweg ME, Ghezzi D, Haack T , et al. Leukoencephalopathy with thalamus and brainstem involvement and high lactate ‘LTBL’ caused by EARS2 mutations. Brain 2012; 135 (Pt 5) 1387-1394
  • 2 Steenweg ME, Vanderver A, Ceulemans B , et al. Novel infantile-onset leukoencephalopathy with high lactate level and slow improvement. Arch Neurol 2012; 69 (6) 718-722
  • 3 Biancheri R, Lamantea E, Severino M , et al. Expanding the clinical and magnetic resonance spectrum of leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) in a patient harboring a novel EARS2 mutation. JIMD Rep 2015; 23: 85-89
  • 4 Kevelam SH, Klouwer FC, Fock JM, Salomons GS, Bugiani M, van der Knaap MS. Absent thalami caused by a homozygous EARS2 mutation: expanding disease spectrum of LTBL. Neuropediatrics 2016; 47 (1) 64-67
  • 5 Talim B, Pyle A, Griffin H , et al. Multisystem fatal infantile disease caused by a novel homozygous EARS2 mutation. Brain 2013; 136 (Pt 2) e228
  • 6 Taylor RW, Pyle A, Griffin H , et al. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA 2014; 312 (1) 68-77
  • 7 Kraut JA, Madias NE. Lactic acidosis. N Engl J Med 2014; 371 (24) 2309-2319
  • 8 Madias NE. Lactic acidosis. Kidney Int 1986; 29 (3) 752-774
  • 9 Mizock BA, Falk JL. Lactic acidosis in critical illness. Crit Care Med 1992; 20 (1) 80-93
  • 10 Haas RH, Parikh S, Falk MJ , et al. Mitochondrial disease: a practical approach for primary care physicians. Pediatrics 2007; 120 (6) 1326-1333
  • 11 Scaglia F, Towbin JA, Craigen WJ , et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics 2004; 114 (4) 925-931
  • 12 Kemp JP, Smith PM, Pyle A , et al. Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency. Brain 2011; 134 (Pt 1) 183-195
  • 13 Cohen RD, Woods HF. Lactic acidosis revisited. Diabetes 1983; 32 (2) 181-191