A Case Relate To The Unique Pathological Changes In The Skeletal Muscle Of A Female With Fabry Disease

Background and objectivesFabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A (a-GalA) due to mutations in the Gal gene. The result is intralysosomal accumulation of glycosphingolipids in several tissue. Traditionally, it was considered as an X-linked recessive disorder. But gradually, several cases about females involved in Fabry disease changed that inaccurate statement.To report a case of Fabry disease about a girl, whose onset occurred as early as age 7, with pathological changes in skeletal muscle and relevant information of her family members. Introduce the characteristic of pathology in skeletal muscle tissue of Fabry disease. Discuss the mechanism of the damage of skeletal muscle of Farby disease.MethodsWe recorded the clinical data of her family members, investigated the skeletal muscle pathology and the activity of Leukocyte α-galactosidase A of the proband and her father. Analysised GLA gene data of her family members.ResultsProband was a 13-year-old Chinese girl who complained about frequent episodes of pain attack and burning sensations in both feet since 6 years ago, The pain could be relieved with oral carbamazepin. Then gradually, she had noticed slight muscle weakness. Her father manifested hypohidrosis since he was a child, and the same abnormal sensation including pain attack and burning appeared 30 years ago. He also suffered from myocardial infarction and ischemic cerebral infarctions 6 and 5 years ago, respectively. There were other 3 male and 5 female in this pedigree had the symptom of this disease which main includes acroparesthesia or burning sensations in the palms of the hands or soles of the feet, angiokeratomas on the skin, kidney dysfunction, Cardiac complications and cerebral ischemic stroke. The muscular pathology of the proband showed a large number of vacuoles containing a material that, on frozen section, stained positively with periodic acid-Schiff stain, suggesting the accumulation of glycosphingolipids in the skeletal muscle tissue, not just underneath the sarcolemma, but also outside the sarcolemma, in the mesenchyme. In contrast, those material only slightly accumulated in the endothelium of blood vessel, perineurium and axon. The muscular pathology of her father showed no problem. The α-GalA activity of the proband and his father were 15.27nmol/lh/mg and 0.33nmol/lh/mg in the Leukocyte of whole blood, respectively (the normal range is 22.9-145.7 nmol/1h/mg). GLA gene analysis revealed that both the proband and her father had a single G-to-C transition in 837 bp of exon 6, was a missense mutation predicting a glutamine to histidine substitution (p. Q279H), heterozygous mutation, which disrupts the normal activity of α-GalA.ConclusionsOnset age of Fabry disease can be early in female. The glycosphingolipids can accumulate extensively in the skeletal muscle and affect it’s function.