OMIM ID:
Combined Oxidative Phosphorylation Deficiency 32
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Ocular signs are common but variable. Patients may not make eye contact and sometimes have disconjugate eye movements. Strabismus (usually exotropia) and nystagmus or often present.
Systemic Features
Six patients from 4 unrelated families of mixed ethnic backgrounds have been reported. Infants within the first 4 to 6 months of life had evidence of developmental delay and neurodevelopmental regression. Poor feeding and breathing difficulties are often noted in this period. Other later signs are axial hypotonia, abnormal movements such as tremor, spasticity, hyperkinetic movements, dystonia with eventual regression of milestones. Joint contractures and kyphoscoliosis may develop.
Microcephaly was noted in several infants and brain imaging in all patients reveals abnormal T2- weighted signals in the brainstem and specifically in the basal ganglia. Decreased activity in muscle mitochondrial respiratory complexes I, III, and IV has been documented. Lactate may be increased in serum and the CSF. Postmortem studies show brain vascular proliferation and gliosis in basal structures.
Genetics
Inheritance
Homozygous or compound heterozygous mutations in MRPS34 (16p13.3) are the basis for this disorder.
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.