OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: PANK2

PANK2
Hallervorden-Spatz disease
Pantothenate kinase-associated neurodegeneration

Movement disorder
Extrapyramidal
Choreoathetosis
Dystonia
Tics
Basal ganglia disease
Pigmentary retinopathy
Optic atrophy
Stuttering
Seizures
Vision loss
Mental deterioration
Spasticity

Pantothenate Kinase 2

Clinical Characteristics

General description (for patients):

This is a progressive neurological disorder of involuntary movements consisting of writhing hand and finger movements, inability to relax muscles, and speech abnormalities including stuttering. Chewing and swallowing become increasingly difficult. The clinical picture resembles Parkinsonism but with onset in childhood. Walking difficulties are often the first evidence of the disease. Tics such as repetitive touching of the hair are common. Patients often are unable to walk by the middle of the second decade. Seizures are uncommon.

Medical description: 

This is the classic disorder of iron deposition in the basal ganglia leading to progressive neurological deterioration.  Symptoms are primarily those of extrapyramidal dysfunction with onset in childhood and relentless progression. Choreoathetoid movements, stuttering and repetitive speech, difficulty chewing and swallowing, rigidity with severe intermittent dystonia, and habitual tics are typical. Corticospinal involvement is seen in 25 per cent.  Seizures may occur but are uncommon. Pigmentary retinopathy and optic atrophy are also features in some patients. Not all patients have the typical manifestations with as many as half being atypical cases with a later onset and more pronounced speech and psychiatric manifestations.

Genetics:

This disorder is caused by defective pantothenate kinase, an essential regulatory enzyme in coenzyme A biosynthesis. The mutations in the PANK2 gene located on chromosome 20 (20p12.3-p13) are responsible. Numerous mutations in PANK2 have been found, many of them missense. An Amish kindred with seven affected individuals in three consanguineous families, consistent with autosomal recessive inheritance, has been reported. A homozygous 7bp deletion in the PANK2 gene was determined to be responsible.

Treatment: 

No treatment is available.

Prognosis:

The disorder is relentlessly progressive.

Ancillary treatments and support:

General supportive care.

Specialists and specialty centers:

Neurologist, pediatrician, ophthalmologist.

References:

Taylor, T.D., Litt, M., Kramer, P., Pandolfo, M., Angelini, L., Nardocci, N., Davis, S., Pineda, M., Hattori, H., Flett, P.J., Cilio, M.R., Bertini, E., and Hayflick, S.J.:  Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13. Nature Genet. 14: 479-481, 2001. PubMed ID: 8944032

Zhou, B., Westaway, S.K., Levinson, B., Johnson, M.A., Gitschier, J., and Hayflick, S.J.:  A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.  Nature Genet. 28: 345-349, 1996.  PubMed ID: 11479594

Hayflick, S.J., Westaway, S.K., Levinson, B., Zhou, B., Johnson, M.A., Ching, K.H., and Gitschier, J.:  Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.  N. Engl. J. Med. 348: 33-40, 2003.  PubMed ID: 12510040

Resources:

NIH-NINDS Information
Hallervorden-Spatz Disease Information

Associated Graphics