Progressive generalized brain atrophy and infantile spasms associated with cytochromec oxidase deficiency

Abstract

Summary Large neutral amino acids (LNAA) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In an open‐label study using LNAA, a surprising decline of blood Phe concentration was found in patients with PKU in metabolic treatment centres in Russia, the Ukraine, and the United States. To validate the data obtained from this trial, a short‐term double‐blind placebo control study was done using LNAA in patients with PKU, with the participation of three additional metabolic centres – Milan, Padua and Rio de Janeiro. The results of the short trial showed significant lowering of blood Phe concentration by an average of 39% from baseline. The data from the double‐blind placebo control are encouraging, establishing proof of principle of the role of orally administered LNAA in lowering blood Phe concentrations in patients with PKU. Long‐term studies will be needed to validate the acceptability, efficacy and safety of such treatment.

Mitochondrial respiratory chain complex IV deficiency presenting as neonatal respiratory distress syndrome

“…As LSFC patients are the largest known cohort with a genetically homogeneous, nuclear encoded congenital lactic acidosis studied,1 further investigation is required into the new phenotypically distinct forms of Leigh syndrome caused by different mutations in the LRPPRC gene. Nevertheless, there is a similar case presentation to the above described by Bakker et al ; a newborn presenting with tachypnoea, feeding difficulties, severe lactic acidosis and a high pyruvate level 5. It could be hypothesised that certain genetic mutations could thus present initially with an elevated pyruvate kinase level, which could be used as an indicator for further investigation into Leigh’s syndrome.…”

Spasms in children with definite and probable mitochondrial disease*

“…Limited attention has been given to the role of mitochondrial disease in infantile spasms. The association between spasms and mitochondrial disorders has been reported mainly in the form of case reports (Boor et al, 1992;Pastoris et al, 1993;Makela-Bengs et al, 1994;Bakker et al, 1996;Verdu et al, 1996). However, a recent study on epileptic phenotypes asssociated with mitochondrial disorders found spasms in 17% of patients (Canafoglia et al, 2001).…”