The Use of Skin Fibroblast Cultures in the Detection of Respiratory Chain Defects in Patients with Lacticacidemia

@article{Robinson1990TheUO,
  title={The Use of Skin Fibroblast Cultures in the Detection of Respiratory Chain Defects in Patients with Lacticacidemia},
  author={B. H. Robinson and D. Moira Glerum and Wendy Chow and Roumyana Petrova-Benedict and Robert N. Lightowlers and Roderick A. Capaldi},
  journal={Pediatric Research},
  year={1990},
  volume={28},
  pages={549-555}
}
ABSTRACT: Cultured skin fibroblasts from patients with lacticacidemia were incubated with glucose for 1 h and the lactate and pyruvate production measured. Those patients with increased lactate to pyruvate ratios were further analyzed for the cause of the abnormal redox state. Two categories of patients are described. The first contains patients with either severe or partial cytochrome oxidase deficiency; this group can be broken down further into patients with Leigh's disease, Kearns-Sayre… 

Figures and Tables from this paper

Diagnosis of complex I deficiency in patients with lactic acidemia using skin fibroblast cultures.
TLDR
This type of rapid preparation, which uses four 9-cm petri dishes of cultured cells, can be used to diagnose mitochondrial complex I deficiency and will find general use in the measurement of either mitochondrial enzymes of low specific activity or mitochondrial enzymes whose measurement is made difficult by contaminating nonmitochondrial enzymes.
Prenatal diagnosis of systemic disorders of the respiratory chain in cultured chorionic villus fibroblasts by study of ATP-synthesis in digitonin-permeabilized cells
TLDR
A simple method based on the use of digitonin-permeabilized fibroblasts which allows accurate assessment of the activity of the oxidative phosphorylation system in fibro Blasts is described and this system can be used advantageously for the prenatal diagnosis of inherited diseases of the respiratory chain.
Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts.
TLDR
The results indicate that the complex I defects in the 2 reported cases are due to nuclear gene mutations.
2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia: Report of a new case
TLDR
Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) deficiency are reported: a girl who died at 10 years and a boy, still alive at 4 years, born to consanguineous parents, which could demonstrate that the E2 component could be responsible for the defect.
...
...

References

SHOWING 1-10 OF 36 REFERENCES
Respiratory chain defects in the mitochondria of cultured skin fibroblasts from three patients with lacticacidemia.
TLDR
The cultured skin fibroblasts from three patients with lacticacidemia were found to have low rates of 1-[14C]pyruvates oxidation in the face of normal pyruvate dehydrogenase activity, and it is concluded that respiratory chain defects can be demonstrated in cultured skin fibreblasts with consistency using a number of different techniques.
Cell culture studies on patients with mitochondrial diseases: Molecular defects in pyruvate dehydrogenase
  • B. Robinson
  • Biology, Medicine
    Journal of bioenergetics and biomembranes
  • 1988
There is a group of inborn errors of metabolism that result in the condition of chronic lacticacidemia of childhood. Nearly all of the defects that can be identified occur in mitochondrial proteins,
Defective intramitochondrial NADH oxidation in skin fibroblasts from an infant with fatal neonatal lacticacidemia.
TLDR
A small-for-gestational-age female infant born at term developed severe lactic acidosis and died on day 13 of life, suggesting a defect in the respiratory chain between NADH and coenzyme Q, for the first time demonstrable in cultured skin fibroblasts.
Cytochrome c oxidase deficiency in leigh syndrome
TLDR
The theory that COX deficiency is an important cause of Leigh syndrome is confirmed, with essentially normal amounts of cross‐reacting enzyme protein in various tissues from different patients.
The molecular basis for the two different clinical presentations of classical pyruvate carboxylase deficiency.
TLDR
It is proposed that the different clinical presentation of human pyruvate carboxylase deficiency is a manifestation of two different mutations in the pyruVate car boxylase gene, one that results in the synthesis of a relatively inactive pyruviate carBoxylase protein CRM(+ve) and one thatresults in the lack of expression of the gene in the form of a recognizable proteinCRM(-ve).
Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin
TLDR
Two infants, second cousins, are reported with a similar fatal mitochondrial disorder, the cytochrome deficiency limited to skeletal muscle in one child and to liver in the other, and the mitochondrial abnormality in the two cousins presumably is related.
Cytochrome c oxidase deficiency.
TLDR
Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening.
Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.
TLDR
This infant is presented as the first reported case of congenital lactic acidosis caused by a deficiency of the iron-sulfur clusters of complex I of the mitochondrial electron transport chain, which was localized in the inner membrane mitochondrial NADH-ubiquinone oxidoreductase (complex I).
Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy.
TLDR
Familial deficiency of a component of mitochondrial NADH dehydrogenase (complex I) proximal to the rotenone-sensitive site thus accounts for this disorder.
Mitochondrial myopathies
Major new advances in the genetic and biochemical characterization of mitochondrial myopathies are discussed, within a general presentation of this important new area of human pathology.
...
...