Contributed by Soo Yeon Kim1+, Jung Min Ko2+, Sun Ah Choi1, Anna Cho3, Jin Sook Lee4, Byung Chan Lim1, Ki Joong Kim1, Jong-Hee Chae1
1Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, and
2Department of Pediatrics, Division of Clinical Genetics, Seoul National University College of Medicine, Seoul Korea
3Department of Pediatrics, Ewha Woman's University School of Medicine, Seoul, Korea and
4Department of Pediatrics, Gachon University Gil Medical Center, Incheon Korea
+Soo Yeon Kim and Jung Min Ko contributed equally as the first author
A 3-month-old boy was referred to our hospital because of slowly progressing weakness, which commenced a month earlier. He was delivered normally from an uneventful pregnancy from nonconsanguineous parents. A neonatal screening test had revealed mildly increased serum carnitine, which was normal in a repeated test. He showed generalized hypotonia with an absence of deep tendon reflexes and a lagged head on neurological examination. During the admission, respiratory muscle weakness progressed and he became dependent on mechanical ventilation with tracheal fenestration. Laboratory tests were unremarkable except for increased aspartate aminotransferase (154 IU/L), alanine aminotransferase (68 IU/L), and creatinine kinase (478 U/L) levels. Multiplex ligation-dependent probe amplifications for SMN1/SMN2, the causative gene for spinal muscular atrophy (SMA) type I, revealed no deletion or duplication. He had additional tests, including metabolic screening, brain MRI, and muscle biopsy. Brain MRI was unremarkable for his age, whereas metabolic screening revealed elevated glutaric acid and ethylmalonic acid in his urine, and elevated plasma C14, C14:1, and C16:1 carnitines.
A muscle biopsy was performed on his left quadriceps. The fibers diameters were remarkably variable. There were many degenerating and regenerating muscle fibers without inflammatory cell infiltration. There was no evidence of fiber type predominance. Many droplet-like structures within muscle fibers were observed on H&E staining (Figure 1a), which appeared as red spots in Oil Red O staining (Figure 1b). What kind of storage myopathy is this?
Although the pathologic findings are non-specific, when combined with the metabolic abnormalities found in the urine and plasma a more specific diagnosis should be suspected. What is the most likely diagnosis and which three genes need to be tested for mutations?