Selected disorders of carbohydrate metabolism

Chapter 10. Myopathies affecting fuel and energy metabolism: Selected disorders of carbohydrate metabolism Definitions of entities The breakdown of glucose (from blood) or intracellular glycogen yields pyruvate that can then enter the TCA cycle (via acetyl CoA in aerobic conditions) or be converted to lactate under ischaemic conditions. Failure in any step in glycogenolysis or glycolysis eliminates or diminishes carbon flux, leading to a rapid decline in high energy phosphates for muscular work, and causing rapid muscle fatigue, cramping, and sometimes rhabdomyolysis. In those conditions where there is a muscle-specific gene product, the symptoms may be restricted to muscle but in other conditions, where there is a single gene encoding the enzyme activity, the effects can be more widespread. Inherited deficiencies in glyogenolytic/glycolytic enzymes are rare, and are usually autosomal recessive. They generally present as exercise intolerance, elevated serum creatine kinase, with rhabdomyolysis and exertion-induced myoglobinuria (3). One of the less well-understood features of this group of conditions relates to the marked variability in the severity of symptoms, even between individuals carrying the same mutations. This suggests that these enzyme deficiencies must be projected onto additional factors influencing muscle capabilities, whether genetic or environmental. In this respect, the anecdotal evidence of greater prevalence/severity in males may be relevant (24). In this chapter, we will consider three of the more common of these conditions: McArdle’s disease, Tarui’s disease, and debrancher deficiency. Some indication of the relative frequencies of these conditions may be gleaned from a survey conducted some years ago as part of the CARMEN programme, (http://carmen. liv.ac.uk). Whilst not intended to be exhaustive, these figures (Figure 1) report the total cases from twenty different muscle clinics within the European community, although these data will reflect local interests.