[P1-150] A girl with psychomotor regression and lactic acidemia with a rare mitochondrial DNA microdeletion m.9204delAT
[Introduction] Mitochondrial disorders are very heterogeneous diseases caused by oxidative phosphorylation (OXPHOS) defects. Besides nuclear DNA mutations, more than 250 pathogenic mitochondrial DNA mutations have been described. m.9204delAT (=m.9205delTA) is a very unique mitochondrial DNA mutation, currently only two clinical reports can be available.
[Case] A 2-year-8-month-old girl with psychomotor regression was referred to our hospital. She had mild psychomotor delay, but could crawl, pull to stand, and imitate others at 18 months of age. After 1 week of fever due to mild gastroenteritis at 2 years of age, she began to lose her skills. Upon referral (8 months after the episode), she was very irritable, always crying with occasional cyanotic spells, and could not even roll over. She showed generalized dystonia, and mildly increased deep tendon reflexes. No retinal lesion was observed. Blood examination revealed elevated lactate and pyruvate levels with metabolic acidemia. Lactate and pyruvate levels were also elevated in cerebrospinal fluid; however, there was no obvious abnormalities detected by MRI. Fibroblast OXPHOS activities (I-IV) were normal.
[Genetic testing] Karyotype: 46,XX; Array-CGH: No significant CNVs; Mitochondrial point-mutation panel: normal; Exome analysis: m.9204_9205delAT, homoplasmy.
[Discussion] We detected a rare mitochondrial DNA microdeletion in a patient with severe psychomotor regression with lactic academia. The patient had been temporarily diagnosed with cerebral palsy due to her dystonia, even though there was no evidence of perinatal injury. Psychomotor regression and lactic acidosis are the hallmark of mitochondrial encephalopathy; therefore, we should consider further genetic testing when conventional approaches couldn’t detect mitochondrial defect.
[Case] A 2-year-8-month-old girl with psychomotor regression was referred to our hospital. She had mild psychomotor delay, but could crawl, pull to stand, and imitate others at 18 months of age. After 1 week of fever due to mild gastroenteritis at 2 years of age, she began to lose her skills. Upon referral (8 months after the episode), she was very irritable, always crying with occasional cyanotic spells, and could not even roll over. She showed generalized dystonia, and mildly increased deep tendon reflexes. No retinal lesion was observed. Blood examination revealed elevated lactate and pyruvate levels with metabolic acidemia. Lactate and pyruvate levels were also elevated in cerebrospinal fluid; however, there was no obvious abnormalities detected by MRI. Fibroblast OXPHOS activities (I-IV) were normal.
[Genetic testing] Karyotype: 46,XX; Array-CGH: No significant CNVs; Mitochondrial point-mutation panel: normal; Exome analysis: m.9204_9205delAT, homoplasmy.
[Discussion] We detected a rare mitochondrial DNA microdeletion in a patient with severe psychomotor regression with lactic academia. The patient had been temporarily diagnosed with cerebral palsy due to her dystonia, even though there was no evidence of perinatal injury. Psychomotor regression and lactic acidosis are the hallmark of mitochondrial encephalopathy; therefore, we should consider further genetic testing when conventional approaches couldn’t detect mitochondrial defect.