Wolfram syndrome: mitochondrial disorder

Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice

“…This hypothesis was based on the clinical observations that the affected tissues and organs in WFS patients have a high metabolic demand and most of the clinical manifestations of WFS are consistent with an ATP supply defect, which is often seen in mitochondria-mediated disorders. There were several studies supporting this hypothesis (Rö tig et al 1993;Vora and Lilleyman 1993;Barrientos et al 1996). Notably, Bundey et al (1992) described a WFS patient having morphologically and biochemical abnormal mitochondria in the muscle biopsy; this finding indicated that a mitochondrial defect may be involved in the pathogenesis of WFS.…”

Thiamine-responsive megaloblastic anaemia syndrome: Long-term follow-up and mutation analysis of seven families

“…Family 2 has a single nucleotide substitution (484C /T) leading to a premature stop codon (R162X) [12]. The patient from family 5 has a single nucleotide insertion (239-240 insA) creating a frame shift mutation resulting in a premature stop codon (R97X) [15]. Families 3, 4 and 6 all have the same single nucleotide substitution (196 G /T) resulting in a premature stop codon (E66X) [12].…”

“…The clinical details of two UK families were originally reported in 1982 and 1993, respectively [14,15] (families 3 and 4, Table I). There is a lack of long-term follow-up data in these patients, so we aimed to describe the long-term follow-up of these original families, the other families of South Asian origin whom we have identified, and to relate clinical features to mutation data.…”

The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia geneSLC19A2 of eight families

“…In addition some patients also have congenital heart anomalies, arrhythmias, and/or abnormalities of the retina. Disease onset is in early childhood, and most of the patients respond to treatment with pharmacological doses of thiamine [Rogers et al, 1969;Viana and Caravalho, 1978;Haworth et al, 1982;Mandel et al, 1984;Borgna-Pignatti et al, 1989;Grill et al, 1991;Vora and Lilleyman, 1993;Rindi et al, 1994;Bazarbachi et al, 1998]. We have recently found mutations in a novel gene, SLC19A2 (MIM# 603941), encoding a putative transmembrane protein homologous to the reduced folate carrier proteins [Labay et al, 1999].…”