Taurine Deficiency and MELAS Are Closely Related Syndromes - Advances in Experimental Medicine and Biology - page 147

16.2.4 Gastrointestinal Defects in MELAS and Taurine

De fi ciency

Common gastrointestinal manifestations of MELAS include abdominal discomfort
and constipation, with vomiting, dysmotility, gastroparesis, malabsorption, and
pseudo-obstruction being less common (Sproule and Kaufmann 2008 ) . Although
the mechanism underlying these complications has not been established, it is inter-
esting that gastrointestinal defects are sometimes accompanied by hepatic dysfunc-
tion, which is found in taurine deficiency.
There have been no studies on the effect of taurine deficiency on the develop-
ment of gastrointestinal defects. Nonetheless, taurine deficiency leads to chronic
liver disease, associated with chronic hepatitis and liver fibrosis (Warskulat et al.
2006 ). The liver defect is caused in part by the loss of hepatocytes through apopto-
sis. However, in contrast to other examples of hepatocyte loss, the cell loss in
taurine-deficient mice does not lead to a stimulation in hepatocyte production, an
effect possibly related to the regulation of checkpoint genes by taurine (Golubnitschaja
et al. 2003 ). Clearly the study of the gastrointestinal effects of taurine deficiency
warrants further investigation.

16.2.5 Hearing Loss in MELAS and Taurine De fi ciency

A maternally inherited family pedigree combining type 2 diabetes and sensorineural
hearing loss has been described (van den Ouweland et al. 1992 ) . The mutation caus-
ing this defect was ultimately shown to be identical to that causing MELAS. Overall,
the frequency of hearing impairment in MELAS is about 0.1% at birth but greater
than 50% by age 80 (Sproule and Kaufmann 2008 ) .
Abnormal auditory brainstem-evoked potential has been detected in taurine-
deficient kittens and preterm infants (Tyson et al. 1989 ; Vallecalle-Sandoval et al.
1991 ). Although these findings implicate taurine deficiency in the development of
the auditory system, there is no firm evidence that taurine deficiency leads to overt
hearing loss (Davies et al. 1994 ). However, it is interesting to note that type II
cochlear afferents are stimulated by ATP (Weiss et al. 2009 ) . Whether the decrease
in ATP production by neurons of MELAS patients or taurine-deficient animals
affects the function of type II cochlear afferents remains to be determined.

16.2.6 Muscle Weakness and Taurine De fi ciency

Myopathy is one of the hallmark symptoms of MELAS (Sproule and Kaufmann
2008 ). In a study by Hirano and Pavlakis ( 1994 ), more than 85% of 110 MELAS
patients examined were exercise intolerant; in a related study 73% of MELAS