Naslov
Remarkable 2-oxoglutaric/2-oxoadipic aciduria as an indeks of respiratory chain complex 1 deficiency

Autori
Maradin, Miljenka ; Fumić, Ksenija ; Sarnavka, Vladimir ; Robinson, BH ; Trijbels, JMF ; Barić, Ivo

Izvornik
Journal of inherited metabolic disease (0141-8955) 25 (2002), Supl 1;

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, kongresno priopcenje, znanstveni

Ključne riječi
2-oxoglutaric aciduria; 2-oxoadipic aciduria; respiratory chain complex

Sažetak
Human complex I deficiency, the most common respiratory chain defect, has variable clinical presentation and can be difficult to diagnose. Although increased excretion of different citrate cycle metabolites is common in respiratory chain disorders, permanent and massive changes are rarely reported. This case seems to be unusual in this sense. A 2-months old girl was referred to us due to muscular hypertonia and absent visual contact. Brain MR showed agenesis of corpus callosum, severe cortical atrophy and dilated occipital parts of lateral ventricles. In the follow-up period microcephaly, controllable convulsions and almost absent development have been the most prominent clinical features. Blood lactate ranged from 3.1 to 4.1 mmol/l with normal lactate/pyruvate ratio. CSF lactate was 5.0 mmol/l. Organic acids analysis repeatedly showed massive excretion of 2-oxoglutaric acid ranging from 578 to 940 mmol/mol creatinine (normal <150). 2-oxoadipic acid was also always clearly elevated, although to a less extent. Other Krebs cycle metabolites were slightly and not constantly elevated as well as 2-OH-glutaric acid. Activity of 2-oxoglutarate dehydrogenase in lymphoblasts was normal. Measurement of muscle PDH complex and respiratory chain enzymes showed isolated deficiency of complex I, while the activity of all enzymes in fibroblasts was normal. No mtDNA mutations were found. This case points to permanent remarkable 2 oxoglutaric/2-oxoadipic aciduria as a possible additional biochemical marker of isolated complex I deficiency.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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