Clinical and Treatment Management Decisions in Two Asymptomatic Late-Onset Pompe Disease Siblings – Further Evidence of Scoliosis as a Clinical Sentinel Sign for Juvenile Pompe Disease

Abstract

disease patient was identifi ed by chance through his dermatologist due to partial alopecia. Through high CK (1,310 IU/L) and muscle/hepatic biomarkers (AST, 162 IU/L; ALT, 189 IU/L) a muscle biopsy was performed revealing vacuolated muscle pathology with H-E and PAS stains. A compound heterozygote pathogenic GAA genotype was detected (-32-13 T>G/ c.2560C>T). A series of clinical and laboratory evaluations identifi ed several abnormal clinical signs, despite the absence of clinical symptoms. As the patient had a positive DBS, diminished GAA activity in leukocytes (0.56 nml/h/mg protein – RV: 1.0–5.9), high urinary GLc4 levels on HPLC, abnormal FVC drop during sitting–supine transition (>14%), and abnormalities on his tongue and edema of his thighs, seen on MRI, the decision was taken to initiate enzymatic replacement therapy (ERT) with 20 mg/kg rhGAA (Myozyme®), even though no subjective clinical symptoms were present. After 4 years on ERT treatment and motor/respiratory rehabilitation programs, all clinical parameters worsened, especially CK levels, muscle MRI with an overall muscle substitution for fat with muscle mass volume reduction; and a higher FVC drop during sitting–supine transiti on (>18%) were noted. Based on these clinical and laboClinical and Treatment Management Decisions in Two Asymptomatic Late-Onset Pompe Disease Siblings – Further Evidence of Scoliosis as a Clinical Sentinel Sign for Juvenile Pompe Disease