Clinical and biochemical diagnostic and therapeutic survey of seven patients with lipid storage myopathy due to glutaric aciduria type II

Objective To investigate the clinical and biochemical profiles of the patients with lipid storage myopathy due to late onset glutaric aciduria type Ⅱ. Methods Seven patients (5 boys and 2 girls) with lipid storage myopathy due to glutaric aciduria type Ⅱ were reviewed. The diagnosis was confirmed by urinary organic acid analysis, blood free fatty acid assay with gas chromatography/mass spectrometry (GC/MS) and acylcarnitine profile by tandem mass spectrometry. Their clinical features, laboratory findings, and treatment were studied.Results These previous healthy patients began to develop progressive fatigue, proximal muscular weakness and pain from an age of 9 to 24 years. Five of them had poor appetite and body weight loss. Three had episodic palpitation. Three had recurrent lethargy. All patients had mild hepatomegly. Mild muscular weakness, hypotonia and absence of deep tendon reflexes were found in 4 of them. A marked elevation of serum CK, CK-MB, LDH, HBDH and a slight increase of lactate, pyruvate and β-OH-butyric acid were observed. A decrease of free carnitine was found in 7 patients. Three had hypoglycemia and ketosis. Mild metabolic acidosis and hyperammonemia were found in one boy. Muscle biopsy revealed lipid storage myopathy in all patients. Two of them had muscle fibers atrophy. Dried blood cis-4-decenoic acid (C10∶1), cis-4-tetradecenoic acid (C14∶1), middle chain and long chain acylcarnitine were significantly increased in all patients. An elevated excretion of 2-hydroxyglutaric acid, 3-hydroxyglutaric acid, 2-hydroxyisovaleric acid, and ethylmalonic acid in urine were confirmed in 4 patients. Ketotic dicarboxylic aciduria was found in 1 patient. All of the patients were responded to large dose of riboflavin (100～500 mg/d) significantly. Carnitine, coenzyme Q_(10) supplementation and protein-restricted diet were given for 1 to 2 months as a supporting therapy. Pronounced and rapid clinical and biochemical improvement was observed. All patients went back school or to work after 1 to 3 months therapy. Conclusions The late onset glutaric aciduria type Ⅱ is characterized by lipid storage myopathy. The adolescent patients might respond to riboflavin significantly. Early diagnosis and adequate therapy could contribute a lot to improve the prognosis of the patients. Urinary organic acid analysis and blood free fatty acid assay should be very helpful to the diagnosis.