5In patient SIH-1, elevated Lactate, Pyruvate, Acetoacetate, 3-OH Butyrate in GC- MS of urine as well as elevated Alanine in blood are strongly suggestive of mitochondriopathy. 6Pyridoxine dependency was suspected clinically as the patient had intractable seizures but patient did not survive long enough to undergo further work up including CSF Pipecolic acid.
Three (30%) patients were suspected to have mitochondriopathy based on biochemical parametres which included elevated lactate in urine or plasma, elevated alanine in plasma amino acids, urine GC-MS showing elevation of one or more of the following compounds; Pyruvate, Succinate, Fumarate, Citrate and Aconitate (a metabolite in Kreb's cycle).
doxorubicin-induced in vivo mitochondriopathy
and reduces the
Despite the availability of many tools to diagnose mitochondrial disease (16, 17), current methods are still insufficient for the evaluation of a large subgroup of patients suspected to have a mitochondriopathy. Here, we show that quenched-fluorescence oxygen sensing provides a fast and efficient additional diagnostic tool that can be used to examine the mitochondrial energy-generating system in cultured patient-derived cells.
Another subgroup of patients showed normal or near-normal oxygen consumption rates in fibroblasts that may be a reflection of a tissue-specific mitochondriopathy, which is not uncommon, e.g., mtDNA mutations with uneven tissue distribution or POLG [polymerase (DNA directed), [gamma], formerly POLG1] gene mutations.
An infant with mitochondriopathy was the probable index patient.
Patient 1 stayed on the same ward and same floor, but not in the same room (distance between the rooms' doors [approximately equal to] 10 m), as an infant with a yet-unclassified mitochondriopathy and pneumonia, which later was diagnosed as PCP Patient 2's hospital stay overlapped that of patient 1; the patients were on the same ward and same floor, in rooms with doors separated by 8 m, before the onset of PCP Patient 3 spent her holiday with patient 2 in a summer camp organized by our Pediatric Nephrology Division.
Pyruvate and Krebs cycle intermediates exist in equilibrium with amino acid pools, and elevation of certain amino acids, such as alanine, can occur in the presence of mitochondriopathy. Unfortunately, the sensitivity of these tests is poor For instance, although lactate elevations may reliably occur with tRNA gene mutation disorders such as MELAS, lactate levels in LHON commonly are normal.
Direct tissue evaluation by the pathologist is still the gold standard for demonstrating the presence of mitochondriopathy. Tissue studies can include direct biochemical measurements of relevant enzyme activities or coenzyme levels, or structural anatomic assessments.
Muscular biopsy in LS patients with late onset may find mitochondriopathy
. However, these changes are rare in infants with early onset.
Perazella, "Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy
," Kidney International, vol.
The method has been used in our center for many years and has demonstrated its merit in the diagnosis of patients suffering from a mitochondriopathy