In 4 Taiwanese patients from 3 unrelated families with glutaric acidemia IIC (MADD; 231680), Liang et al. (2009) identified a 250G-A transition in exon 3 of the ETFDH gene, resulting in an ala84-to-thr (A84T) substitution. One patient was homozygous for the mutation, whereas the other 3 were compound heterozygous for A84T and either a 524G-T transversion, resulting in an arg175-to-leu (R175L; 231675.0004) substitution (2 sibs) or a 380T-A transversion, resulting in a leu127-to-his (L127H; 231675.0005) substitution. All 3 mutations affected highly conserved residues in the FAD-binding domain. The R175L and L127H mutations were not identified in 200 Taiwanese control chromosomes. The A84T variant was identified in 1 of 200 Taiwanese control chromosomes but not in 100 Japanese, 100 Korean, and 100 Thai control chromosomes. No specific haplotype could be linked to the A84T variant.
Lan et al. (2010) identified homozygosity for the A84T mutation in 6 of 7 Han Taiwanese patients with MADD. The patients had a variable phenotype. The age at diagnosis ranged from 7 to 43 years, and the patients' ages at the time of the report were between 22 and 44 years. All had a history of episodic myalgia and limb weakness predominantly affecting the proximal muscles during an acute stage of myopathy. Four had dysphagia and 2 had respiratory failure. Serum creatine kinase was increased during the acute attacks. Three had 1 episode, whereas 4 had recurrent episodes. Four patients had extramuscular features. All except 1 regained normal muscle strength after the acute stage. Trigger factors in some patients included prolonged fasting and exercise. Blood analysis showed increased acylcarnitines ranging from C8 to C16. A seventh Han Taiwanese patient with the disorder was compound heterozygous for A84T and a 524G-A transition in the ETFDH gene, resulting in an arg175-to-his (R175H; 231675.0006) substitution in a highly conserved residue in the FAD-binding domain.
