Glycogen Storage Disease Xi

A number sign (#) is used with this entry because glycogen storage disease XI (GSD11), or lactate dehydrogenase A deficiency, is caused by homozygous mutation in the LDHA gene (150000), which encodes lactate dehydrogenase, on chromosome 11p15.

Clinical Features

Kanno et al. (1980) described a family with deficiency of the muscle (M) isoform of LDH (LDHA). The proband was an 18-year-old male who complained of exertional myoglobinuria and easy fatigue. Ischemic work of the forearm was accompanied by increased blood lactate, pyruvate, and serum creatine kinase, with myoglobinuria. Maekawa et al. (1984) reported 2 Japanese daughters, born of first cousins, with homozygous LDHA deficiency.

Kanno et al. (1988) studied carbohydrate metabolism in 3 Japanese families with LDHA deficiency. A total of 8 individuals (4 male, 4 female) were affected. In 1 family, which had not previously been reported, the proband was a 23-year-old male who was easily fatigued and had renal failure dating from the age of 13 years. Painful muscle stiffness and cramps had first been noted at age 9 during a 100-meter dash. A sister likewise had complete absence of LDHA.

Yoshikuni et al. (1986) reported 2 adult Japanese patients with myoglobinuria and easy fatigability after strenuous exercise due to deficiency of LDHA. They also had characteristic nonpruritic erythematosquamous skin lesions on the extensor surfaces of the extremities since childhood, showing some improvement after puberty. Takayasu et al. (1991) reported a 16-year-old Japanese girl who had desquamating erythematosquamous lesions mostly on the extensor surface of the extremities, mild muscle pain after strenuous exercise, and complete lack of LDHA in red cells. The epidermis of the diseased skin and scalp hair follicles were virtually devoid of LDH activity. Both parents, who were related as second cousins, had decreased red cell LDHA.

Molecular Genetics

In a woman with glycogen storage disease XI reported by Maekawa et al. (1986), Maekawa et al. (1990) found homozygosity for a 20-bp deletion in exon 6 of the LDHA gene (150000.0001). Maekawa et al. (1990) noted the that woman 'frequently complained of uterine stiffness during her pregnancy. Uterine stiffness was a problem in the early stage of delivery and, thus, she required a Caesarean section.'

Maekawa et al. (1991) demonstrated the same LDHA mutation in 18 persons from the 4 known affected families in Japan.

Miyajima et al. (1993) identified the exon 6 deletion in 2 adult Japanese sisters that had muscle stiffness following strenuous exercise since the teens and age 9, respectively. Both had had cesarean sections because the 'uterus was too stiff in the early stage of delivery.'

Population Genetics

In a survey of 3,776 healthy persons in Shizuoka Prefecture in Japan, Maekawa et al. (1984) found the frequency of heterozygous LDHA and LDHB subunit deficiencies to be 0.185% (about 1 in 540) and 0.159% (about 1 in 630), respectively. These frequencies were probably higher than in most other populations.