OMIM ID:
Spastic Ataxia 4, mtPAP Deficiency
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Ocular examinations in 4 adult individuals of a single family aged 18 to 27 years were reported to have optic atrophy. One of these had a horizontal nystagmus and another was described as having a vertical nystagmus. No ocular evaluations were available for 2 children, aged 2 and 6 years. Visual acuity testing was not reported but all individuals participated appropriately in family and educational activities.
Systemic Features
This is a congenital disorder with cerebral ataxia (limb and truncal), spastic paraparesis (increased lower limb tone with brisk knee jerks and extensor plantar responses), cerebellar and spastic dysarthria, learning difficulties and emotional lability as prominent features. The onset of both speech and mobility are delayed. Older individuals have slow and spastic tongue movements with brisk jaw jerks, and increased tone in the upper limbs. Motor function progressively declines although even older individuals in the third decade of life remain mobile albeit with an increasingly spastic and ataxic gait, and require only minimal assistance with self-care. Children in grade school require special education accommodations but there is no obvious deterioration in intellectual function as they mature.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from homozygous mutations in the MTPAP gene (10p11.22). The mutation leads to a defect of mitochondrial mRNA maturation in which the poly(A) tails are severely truncated.
Optic atrophy is also present in some patients who have autosomal dominant spastic ataxia with miosis (SPAX7) (108650) and in another form of autosomal recessive childhood-onset spastic ataxia and mental retardation (270500).
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.