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Leigh/Leigh-like Syndrome - MTATP6, PDHA1, SURF1

subacute necrotising encephalopathy

Clinical Features

Leigh Syndrom (LS) or "subacute necrotizing encephalomyopathy" was first described by the pathologist, Denis Leigh in 1951. She described the typical symmetric brain lesions in the bilateral basal ganglia and brainstem in one of the most frequently occurring mitochondrial encephalomyopathy. Approximately 70% of the patients show deficiency of the respiratory chain complexes I-IV, and ca. 15% is caused by pyruvate dehydrogenase deficiency.

 

Beside the typical Leigh syndrome, several patients show Leigh-like MRI lesions in the basal ganglia, in the cerebral white matter and/or in the cerebellum and peripheral neuropathy might be also present. These cases are called Leigh-like disease.

Other organs might be also affected by the disease, like heart, liver or kidney. The disease onset is usually before 2 years of age, but it can vary between birth and adult age.

Genetic Information

The genetic defect can be identified in approximately 40% of cases with Leigh syndrome, mutations in several different nuclear or mitochondrial genes might be present. Most frequently, mutations in SURF1 are related to Leigh syndrome. The wide spectrum of possible genetic defects in Leigh syndrome makes direct genetic analysis of blood DNA in these patients difficult. The biochemical measurements of the respiratory chain enzymes in muscle tissue can narrow the number of possible genes and help genetic diagnostics in this disease.

 

Summary of the possible genetic causes of Leigh syndrome:

Leigh/Leigh-like syndrome with

  • complex I deficiency: mtDNA ND genes, nuclear complex I subunit gene
  • complex II deficiency: SDHA
  • complex III deficiency: BCS1L
  • complex IV (COX) deficiency: SURF1, COX10, COX15, SCO1
  • complex IV (COX) deficiency with cardioencephalomyopathy: SCO2
  • complex V deficiency: mtDNA ATPase6, ATPase8

Prevalence

The incidence of Leigh syndrome in West-Sweden is ca. 1 : 10 000,
the prevalence in North-Spain is 2,05 : 100 000.

 

Diagnostic

 

Indication

Leigh/Leigh-like-Syndrom with biochemical result

Method

Mutation analysis of the entire coding and flanking intronic regions with intronic primers of the following genes depending on the respiratory enzyme defect: SURF1, SCO2, SCO1, COX10, COX15, SDHA, BCS1L  and  mtDNA ND or ATPase genes by direct DNA sequencing.

Sample Requirement

2 - 4 ml of EDTA-blood

Duration

2 - 6 weeks

OMIM

249270 Leigh Syndrome



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