Infantile myopathy and lactic acidosis


Infantile myopathies are associated with severe cytochrome c oxidase (COX) deficiency. These are transmitted as autosomal recessive traits, but the affected genes remain unknown.

The infantile myopathy and lactic acidosis is a primary mitochondrial disease, consequence of dysfunctions of both mitochondrial and nuclear genes either separately or in combination. As a result, oxidative phosphorylation is defective. 

The disease results from a congenital defect in COX. Defects in cytochrome-c oxidase caused by mutations in the SCO2 result in the fatal infantile cardioencephalomyopathy. 


1. Salvatore Di Mauro et al., Mitochondrial Myopathies, Basic Appl Myol 13 (3): 145-155, 2003 

2. Prof. Isidro Ferrer, Institut Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, CIBERNED, Hospitalet de LLobregat; Spain

3. U.S. National Library of Medicine,



The infantile myopathy and lactic acidosis is a COX-deficient myopathy. The myopathy presents two main variants:

1. Fatal infantile myopathy. May begin soon after birth and accompanied by:

  • hypotonia
  • weakness
  • lactic acidosis
  • ragged-red fibers
  • respiratory failure
  • kidney problems.

2. Benign infantile myopathy. May begin soon after birth and accompanied by:

  • hypotonia
  • weakness
  • lactic acidosis
  • ragged-red fibers
  • respiratory problems, but (if the child survives) followed by spontaneous improvement.

In general hypotonia, feeding and respiratory difficulties are common in the fatal and non-fatal form.


Quantitative errors in mtDNA (mtDNA depletion). Cytochrome c oxidase deficiency is caused by a defect in Complex IV of the respiratory chain. Dysfunctions of both mitochondrial and nuclear genes resulting in severe cytochrome c oxidase (COX) deficiency.


To ensure children would not inherit mitochondrial DNA mutations, genetic testing of IVF embryos for known genetic diseases allows the clinician to identify, before implantation, those embryos that carry the genetic mutation for disease.

IVF be used to prevent transmission of mitochondrial disease by creating a hybrid egg from the intended mother’s nuclear DNA and a donor egg, which substitutes the mother’s mutated mitochondrial DNA with normal mitochondrial DNA from a donor egg.

How it works: Because the DNA is nicely encapsulated in the egg’s nucleus, the entire nucleus can be removed fairly easily using micromanipulation tools similar to the tools routinely used in IVF clinics for intracytoplasmic sperm injection (ICSI). The technical aspects of removing a cell nucleus and putting it in an de-nucleated egg has been in use for decades for various research applications. The nucleus inside the donor egg is removed and discarded, leaving behind a donor egg containing mitochondrial DNA and donor cytoplasm. The nucleus is also removed from the intended mother’s egg but in this case, the rest of the egg is discarded, saving only the maternal nucleus. Then the maternal nucleus is transplanted into the de-nucleated donor egg, reconstituting a complete egg which then is fertilized via IVF using sperm from the biological father.



In some individuals, the clinical picture is characteristic of a specific mitochondrial disorder (e.g., LHON, NARP, or maternally inherited LS), and the diagnosis can be confirmed by molecular genetic testing of DNA extracted from a blood sample. In many individuals, such is not the case, and a more structured approach is needed, including family history, blood and/or CSF lactate concentration, neuroimaging, cardiac evaluation, and muscle biopsy for histologic or histochemical evidence of mitochondrial disease, and molecular genetic testing for a mtDNA mutation.

Even if the diagnosis is not obvious, the following studies can be used to help guide the diagnostic process:

  • Family history: especially if a maternal inheritance pattern is present.
  • Neuroimaging studies: CT and MRI.
  • Functional studies: brain stem dysfunction, abnormal BAERS/VERS/EEG, increased signal in the basal ganglia, delayed myelination, white matter abnormalities, cerebellar
  • atrophy and lactate elevation on magnetic resonance spectroscopy (MRS).
  • Laboratory investigations: lactate, pyruvate, lactate/pyruvate ratio, alanine, acylcarnitine
  • profile and urine organic acids.
  • Muscle, liver and/or heart biopsy: assay of electron transport chain activity, light microscopy, and electron microscopy.
  • Genetic testing


Children with fatal infantile myopathy have a profound neonatal hypotonia and weekness, with severe lactic acidosis, and die of respiratory failure before one year of age.

Children with begnin infantile myopathy also present with severe generalized  weekness; they require assisted ventilation, but improve spontanously and appear normal by two or three years of age. Lactic acidosis, which is initially even more severe than in the fatal form, also remits spontanously.

Source: Anthony H. V. Schapira, Mytochondrial Function and Dysfunction, International Review of  Neurobiology, Volume 53, 217-219


There is currently no available disease-modifying therapy for mitocondrial myopathies. Several agents (mostly nutritional supplements) have been investigated with double-blind, placebo-controlled studies. These include carnitine, creatine, CoQ10, cysteine, dichloroacetate, dimethylglycine, and the combination of creatine, CoQ10, and lipoic acid. None has demonstrated efficacy in clinical disease end-points, although numerous non-blinded studies andcasereportshavesuggestedefficacy.

Kollberg and Holme (2009) demonstrated that an antisense oligonucleotide specifically targeting activated cryptic splice sites in the ISCU gene induced by mutation (611911.0001) was able to restore the correct reading frame in cultured fibroblasts derived from patients with homozygous mutation. The restoration in cells was stable, with correctly spliced mRNA remaining the dominant RNA species after 21 days.


The following selected disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.


  • Children's European Mitochondrial Disease Network

Mayfield House

30 Heber Walk

Northwich CW9 5JB

United Kingdom

Phone: +44(0) 01606 43946 (Helpline)

Email: [email protected]

  • National Library of Medicine Genetics Home Reference
  • Leber hereditary optic neuropathy
  • National Library of Medicine Genetics Home Reference
  • Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
  • National Library of Medicine Genetics Home Reference
  • Neuropathy, ataxia, and retinitis pigmentosa
  • United Mitochondrial Disease Foundation (UMDF)

8085 Saltsburg Road

Suite 201

Pittsburg PA 15239

Phone: 888-317-8633 (toll-free); 412-793-8077

Fax: 412-793-6477

Email: [email protected]

  • International Foundation for Optic Nerve Disease (IFOND)

PO Box 777

Cornwall NY 12518

Phone: 845-534-7250

Fax: 845-534-7250

Email: [email protected]

  • Muscular Dystrophy Association - USA (MDA)

3300 East Sunrise Drive

Tucson AZ 85718

Phone: 800-572-1717

Email: [email protected]

  • Mitochondrial Disease Registry and Tissue Bank

Massachusetts General Hospital

185 Cambridge Street

Simches Research Building 5-238

Boston MA 02114

Phone: 617-726-5718

Fax: 617-724-9620

Email: [email protected]

RDCRN Patient Contact Registry: North American Mitochondrial Disease Consortium

Patient Contact Registry