Contributed by Jantima Tanboon1, Sorawit Viravan2, Yukiko K. Hayashi3, 4, Ichizo Nishino3, Tumtip Sangruchi1
1Departments of Pathology and 2Pediatrics, Division of Neurology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand,
3Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan
4Department of Neurophysiology, Tokyo Medical University, Shinjuku, Tokyo, Japan
A 2-month-old male infant was referred to our hospital due to congenital hypotonia. The patient was normally delivered at 42 weeks of gestation age to a 20-year-old healthy mother. He was the first child of this family. Based on regular antenatal care, no abnormal findings were reported until birth when the APGAR scores at 1 and 5 minutes were 4 and 7, respectively. He had 2,850 g birthweight, 49 cm crown heel length, and 34 cm head circumference. The patient was hypotonic and had respiratory distress which required endotracheal intubation soon after delivery. Physical examination revealed generalized hypotonia. Myopathic facies without high-arched palate was noted. There was no evidence of metabolic disorders. Serum creatine kinase level was normal (56 IU/L). Serology tests for congenital infections were negative. SMN gene analysis displayed no mutation suggestive of spinal muscular atrophy. There was no evidence of consanguineous marriage in his family. The mother and her sister are clinically normal. The mother's male siblings passed away at 1 month and 1.5 months after birth due to respiratory distress complicated by respiratory infection (Figure 1).
Muscle biopsy was performed on the left quadriceps. Most fibers were round in shape and small in size; the maximum diameter was 10 Ám. Fibers with central and internalized nuclei were common (Figures 2 and 3). There was also slight increased endomysial and perimysial connective tissue. There was no evidence of necrosis, regeneration, or inflammation in the biopsy specimen. The type 1 fibers were predominant. Fibers with a dark central region and peripheral halo were demonstrated in periodic acid-Schiff (PAS) (Figure 4), modified Gomori trichrome (not shown), reduced nicotinamide adenine dinucleotide tetrazolium reductase (Figure 5), and other stains for oxidative enzymes (not shown). Ultrastructural study revealed nuclei in the center of the small muscle fibers with well-arranged myofibrils at their periphery (Figure 6).
MOLECULAR GENETICS STUDY
Genetic analysis of MTM1 gene using genomic DNA revealed a previously reported hemizygous c.141-144delAGAA (p.Glu48fs) in exon 4. His mother had the same deletion mutation, in heterozygous mode (Figure 7). What is your diagnosis?