Combined Oxidative Phosphorylation Deficiency 32
Patient Information
Characteristics
Background and History
This is a recently reported severe inherited brain development disorder so far reported in 4 families of mixed ethnic background.
Clinical Correlations
Several infants were noted to have small heads (microcephaly) and poor eye contact from birth but these are inconsistent features. By 4 to 6 months of age poor feeding and breathing difficulties are usually evident. Developmental delays and regression in milestones becomes apparent. Abnormal accelerated and writhing movements, as well as tremors become evident. Truncal weakness is often evident but stiffness and increased reflexes in the limbs can occur at the same time. Contractures of the joints and abnormal curvature of the spine may develop. Inability to walk and speak is common.
MRIs of the brain show widespread abnormal architecture and muscle studies show poor function of respiratory enzymes while a substance known as lactate is increased in the blood serum and in the spinal fluid.
Genetics
Inheritance
This is an autosomal recessive disorder in which mutations are present in both members of a specific gene. Parents with one mutation are clinically normal but if both carry one copy of the mutation, each of their children have a 25% risk of developing this condition.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
Diagnosis and Prognosis
The small head may call attention to this disorder at birth but this is a nonspecific sign. It is more likely that the diagnosis is made during the first 6 six months based on the complete clinical picture of the lack of neurological development. Pediatricians, ophthalmologists, and perhaps radiologists are most likely to collaborate in the diagnosis and care of these infants. Seizures have not been reported.
No treatment of the general condition has been reported. Several infants have died in the first year of life but at least one lived into the second decade.
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