OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: MTPAP

MTPAP mutation
MTPAP SA

Spastic ataxia
Mental retardation
Psychomotor delay
Spastic paraparesis
Dysarthria
Optic atrophy
Cognitive impairment
Learning difficulties

Spastic Ataxia 4, mtPAP Deficiency

Clinical Characteristics

General description (for patients):

This is a neurological disorder with symptoms of unsteadiness and delayed speech and walking from early childhood. It is slowly progressive with older individuals having more stiffness in the arms and legs. Walking is unsteady but most individuals remain mobile into adulthood. Speech becomes more slurred over time but mental functioning, while moderately impaired, remains relatively stable. Mental retardation was documented in one patient but self-care requires little assistance.

Medical description:

This is a slowly progressive disorder of motor and mental dysfunction. Speech and walking are delayed from the outset. Cerebellar ataxia (limb and truncal) and spastic paraparesis are apparent at an early age with brisk knee jerks and extensor plantar responses. Speech becomes dysarthric. Mobility is maintained into adulthood and most need only mild assistance in self-care. Learning difficulties and cognitive defects necessitate special education assistance in grade school. IQ on formal testing in one 12 year old was recorded at 47. Optic atrophy has been observed in several individuals although visual acuity has not been measured.

Genetics:

This autosomal recessive disorder results from a mutation in MTPAP (10p11.23). This nuclear-encoded gene is important for mitochondrial mRNA maturation and function.  Six affected individuals ages 2 to 27 years old from an Amish community in Ohio have been reported.

Treatment:

No treatment beyond supportive care is available.

Prognosis:

The prognosis is reasonably good with no impact on longevity documented. Mental function seems to deteriorate slowly if at all, at least into the third decade of life.

Ancillary treatments and support:

Special education for academics, physical therapists for muscle control.

Specialists and specialty centers:

neurologist, ophthalmologist, pediatrician.

References:

Crosby, A.H., Patel, H., Chioza, B.A., Proukakis, C., Gurtz, K., Patton, M.A., Sharifi, R., Harlalka, G., Simpson, M.A., Dick, K., Reed, J.A., Al-Memar, A., Chrzanowska-Lightowlers, A.M.A., Cross, H.E., and Lightowlers, R.N.: Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am. J. Hum. Genet. 87(5): 655-60, 2010.  PubMed ID: 20970105