E-POSTERS – EARLY ONSET MUSCLE DISEASE – CASE REPORTS: EP.120ADSSL1 distal myopathy presenting with a more rapid progressive course in patient with trisomy 21

Abstract

We report a 22 year old female of mixed European and Mexican background with novel compound heterozygous ADSSL1 gene mutations (p.Gly326Asp, pat and c.1202+1G>A, mat) identified by exome sequencing with a more progressive clinical course due to her other diagnosis of trisomy 21 (T21). Her development was appropriate for T21, but she never learned to run, jump or use stairs independently. At age 8 yr, her motor skills started to regress with emergence of weakness. She used a walker by 10 yr and lost ambulation at 12 yr. Currently, she cannot weight-bear (strength 1/5 in most leg muscles; quadriceps at 1-2/5), but has more preserved upper extremity use (strength 3 to 3-/5 range). She has hip, knee contractures, end-grade elbow contractures, and coexistence of finger flexor contractures with laxity in PIP and DIP joints. Her cognitive delays are typical for T21. She developed progressive scoliosis that required T4-L4 spinal fusion at 12 yr of age. There is no cardiomyopathy and her LVSF is 36%. Nocturnal hypoventilation started at age 13 yr with use of BiPAP during sleep since 16 yr of age. Unlike previously reported cases, she had a normal CK and her muscle biopsy at 14 yr did not show rimmed vacuoles or nemaline rods but rather severe myopathic changes: fibrosis and adipose infiltration, variation in fiber size with small, atrophic fibers intermixed with hypertrophic fibers, rounded and splitting fibers, increased central nuclei and occasional degenerating/regenerating fibers. To date, ADSSL1 gene mutations, encoding an enzyme converting inosine monophosphate (IMP) to adenosine monophosphate (AMP), have been reported only in 9 Korean patients from 6 families with 8 of the 9 patients having the same compound heterozygous mutations, suggesting a founder-effect. Identification of another patient with novel mutations suggests that this form of myopathy is panethnic and likely underdiagnosed among patients presenting with signs of generalized and distal myopathy.