Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating
neurotransmitters and various other
biogenic amines. Patients deficient in one or both
enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF
serotonin 4-6 times normal, with elevated O-methylated
amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood. These mice show significantly increased monoamine levels, particularly
serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated
serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe
intellectual disability and unusual episodes of
hypotonia, which resemble
atonic seizures, but have no EEG correlate. A customized low dietary
amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient's cardiovascular health through dietary manipulation. Even though a diet low in
tyramine, phenylethylamine, and
dopa/
dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of
serotonin in blood, serum, urine, and CSF while on this diet.
Serotonin biosynthesis inhibitors like
para-chlorophenylalanine and
p-ethynylphenylalanine may be needed to lower
serotonin levels in patients with absent
monoamine oxidase enzymes.