OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: SPG21

Maspardin mutation
HSP
Spastic paraplegia 21

Spastic paraplegia
HSP
Dementia
Motor neuron disease
Spasticity

Mast Syndrome

Clinical Characteristics

General description (for patients):

This disorder was first reported in Holmes County, OH, in 1967, and, as yet, none have been found outside the Amish and none without genealogical connections to Holmes County ancestors. The youngest individual seen was 20 years old probably because few symptoms are obvious in the first two decades of life. Often, however, relatives recall some clumsiness, and perhaps some mental slowness beginning around 11-14 years of age. Others may do well in grade school with mental slowness developing late in teenage years. Sometimes the start of walking is delayed but many are apparently not handicapped in physical activities until late in the second decade. Virtually all are clumsy or unsteady in their twenties, while their affect becomes flat and bland at about the same time with loss of spontaneity and initiative. Severe slurring of speech is almost always evident at that time as well. Physical and mental deterioration is relentlessly progressive and by the fourth decade, all are severely handicapped and often unable to care for themselves. Lifespan is probably not significantly shortened.

Medical description: 

This is an autosomal recessive motor neuron disease accompanied by mental deterioration with inevitable progression to complete incapacitation. No affected individuals under the age of 20 have been examined but there is always a history of gait and mental problems prior to that time. There is often hyper-tonicity in the lower extremities, sometimes accompanied by marked extensor rigidity and clonus, and in half of the cases present in the upper extremities as well. Bradykinesia and and slow involuntary, writhing movements of the fingers are common. Muscle wasting has not been seen. Onset of walking may be delayed, while “clumsiness” in childhood is frequently noted by family members. Slurred speech is a childhood feature in virtually all cases. Cerebellar signs are mild if present. No sensory deficits have been identified. All clinical symptoms worsen, sometimes rapidly.   Gait becomes wide-based, facies become bland, and loss of mental spontaneity leads to akinetic mutism. Total incapacitation occurs by the fifth decade when locomotion is lost and patients lose all self-help initiative. Severe bed-ridden spasticity sets in and total custodial care is required. MRI scans in three patients showed a thin corpus calllosum, plus cerebral and cerebellar atrophy with white matter hyperintensity compatible with demyelination. Nerve conduction studies have been normal. No diagnostic test other than genotyping is available.

Genetics:

All affected cases identified so far have been homozygous for a single base-pair insertion (601insA) in the gene SPG21 located on chromosome 15. The encoded protein (maspardin) is prematurely terminated leading to loss of function.

Treatment:

There is no treatment known to prevent or delay the symptoms. Supportive care is helpful early, but eventually total physical care is required. It is unknown if physical therapy might be helpful in early stages.

Prognosis:

Physical and mental deterioration are relentless.

Ancillary treatments and support:

It would seem that some physical therapy might be helpful but there is no data to support this. Swallowing becomes difficult, and percutaneous enterogastrostomy may be required.

Specialists and specialty centers:

This disorder has only been found in Ohio. The largest number of cases has been seen by medical personnel of the Windows of Hope working in the Holmes County community.  Nutritionists and neurologists should be consulted.

References:

Cross, H. E.; McKusick, V. A. The Mast syndrome: a recessively inherited form of presenile dementia with motor disturbances. Arch. Neurol. 16: 1-13, 1967. PubMed ID: 6024251

Simpson, M.A., Cross, H., Proukakis, C., Pryde, A., Hershberger, R., Chatonnet, A., Patton, M.A., and Crosby, A.H.: Maspardin is mutated in Mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia. Am. J. Hum. Genet. 73: 1147-1156, 2004.  PubMed ID: 14564668

Resources:

Spastic Paraplegia Foundation