Case presentation: A 9-year-old Brazilian girl, second child of healthy non-consanguineous parents,
born full term after an uneventful pregnancy and delivery. Family history was unremarkable.
Developmental milestones were achieved without delay. She presented to our service
at the age of 7 with a history of difficulty walking, climbing stairs and frequent
falls since the age of 3 associated with truncal ataxia and lumbar pain. First neurological
examination revealed myopathic gait, with retained reflexes, unimpaired balance and
coordination. There were no other abnormalities on the physical exam. She evolved
with worsening of dorsal pain but had no episodes of overt rhabdomyolysis. The first
reassessment, 6 months later, physical examination showed slight worsening of proximal
hip girdle weakness, reflexes become hypoactive in superior and hyperactive in lower
limbs. Complementary tests showed: normal EKG, minimal degree tricuspid valve regurgitation
on echocardiogram. Baseline blood investigations were normal. Plasma CK level: 324
U/L (normal range 32–211U/L). EMG was normal. Neuromuscular directed genetic panel
was performed and revealed two variants, heterozygous state, in MSTO1 gene: c.887_888delTT;p.(p.Leu296Argfs*26),
classified as likely pathogenic and c.1115C>T;p.(p.Ala372Val), classified as variant
of uncertain significance (VUS).
Discussion: MSTO1 pathogenic variants have been shown to cause clinical manifestations suggestive
of mitochondrial dysfunction, an extremely rare condition characterized by early-onset
myopathy and cerebellar ataxia. Both autosomal dominant and recessive modes of inheritance
have been suggested. Patients with biallelic MSTO1 mutations presented with a quite
homogeneous phenotype, characterized by early-onset muscle impairment and ataxia in
all, whereas retinopathy, facial dysmorphisms or skeletal abnormalities were variably
present. It is noteworthy that patients present different evolutions, and like our
patient, others present with a relatively stable or slowly progressive condition,
which may mimic other causes. Cognitive impairment is also described in these patients
but not present in our patient.
Final comments: We report a rare case of mitochondrial myopathy and ataxia due to compound heterozygous
MSTO1 mutation, clinically characterized by muscle weakness, myalgia and ataxia. This
clinical phenotype matches the few cases described in current literature and, to date,
the first Brazilian case of this condition.
