DGM (Dutch-German Mennonite)

HUT (Hutterite)

Inheritance: autosomal recessive; mitochondrial
Genes: mt3197T>C

LS
Necrotizing encephalopathy
Infantile subacute necrotizing encephalopathy
SNE
Mitochondrial complex deficiency (all types)

Progressive weakness
Developmental delay
Developmental regression
Spasticity
Mental retardation
Unsteadiness
Ataxia
Respiratory dysfunction
Bulbar dysfunction
Floppiness
Mitochondrial disease

Leigh Syndrome

Clinical Characteristics

General description (for patients): 

This is a severe and often fatal neurologic disorder due to deficiencies in energy enzymes.  Multiple types exist including some that primarily affect infants and young children.  Failure to thrive, generalized floppiness and weakness are often early signs, while swallowing and breathing difficulties soon occur as well.  Unsteadiness can also be a feature.  Developmental delay and mental retardation are common.

Medical description: 

The subacute necrotizing encephalomyelopathy described by Leigh is now recognized as a clinically heterogeneous group of disorders that is due to a group of nuclear and mitochondrial mutations  that impact energy metabolism. The major symptoms result from a progressive neurodegenerative process causing multifocal lesions primarily in the brainstem and spinal cord.  Symptoms depend on the specific areas involved but generally relate to bulbar, cerebellar, and respiratory functions.  Dysphagia and apnea can be prominent symptoms with early weakness and general hypotonia followed by spasticity and hyperreflexia.  Depending upon the enzyme complex involved, blood pyruvate and lactate may be elevated as a result of the impact on the respiratory chain.

Genetics:

Mutations causing Leigh syndrome occur in both nuclear- and mitochondrial-encoded genes responsible for energy metabolism. A mitochondrial mutation (mt3197T>C) has been found in Canadian Mennonite sibs.  Mitochondrial diseases are transmitted to all offspring but only by the mother as sperm do not transfer mitochondria.

Treatment:

There is no effective treatment.

Prognosis:

Poor. Affected infants and children usually die before adulthood.

Ancillary treatments and support:

General support

Specialists and specialty centers:

Pediatrician, Respiratory Therapist

References:

Huntsman, R.J., Sinclair, D.B., Bhargava, R., and Chan, A.:  Atypical presentations of Leigh syndrome: a case series and review.  Ped. Neurol. 32: 334-340, 2005. PubMed ID: 15866434

Leigh, D:  Subacute necrotizing encephalomyelopathy in an infant.  J. Neurol. Neurosurg. Psychiat.  14: 216-221, 1951.  PubMed ID: 14874135

DiMauro, S., and Schon, E.A.:  Mitochondrial respiratory-chain diseases.  New Eng. J. Med.  348: 2656-2668, 2003.  PubMed ID: 12826641

Lee, H.F., Tsai, C.R., Chi, C.S., Lee, H.J., and Chen, C.D.:  Leigh syndrome: Clinical and neuroimaging follow-up.  Ped. Neurol.  40: 88-93, 2009.  PubMed ID: 19135620

Resources:

NINDS Leigh's Disease

Associated Graphics