motor deficits

Spinocerebellar Ataxia 7

Clinical Characteristics
Ocular Features: 

Pigmentary changes in the retina are somewhat variable but often begin with a granular appearance in the macula and spread into the periphery.  The macula often becomes atrophic and dyschromatopsia is common.   Retinal thinning is evident, especially in the macula.  Decreased visual acuity and loss of color vision are early symptoms and the ERG shows abnormalities of both rod and cone function.  External ophthalmoplegia without ptosis is a frequent sign.  Most adults and some children eventually are blind. 

Systemic Features: 

Symptoms of developmental delay and failure to thrive may appear in the first year of life followed by loss of motor milestones.  Dysarthria and ataxia are nearly universal features while pyramidal and extrapyramidal signs are more variable.  This can be a rapidly progressive disease and children who develop symptoms by 14 months are often deceased before two years of age.  However, adults with mild disease can survive into the 5th and 6th decades.  Peripheral neuropathy with sensory loss and motor deficits are usually present to some degree but the range of clinical disease is wide.  Cognitive decline and some degree of dementia occur sometimes. 

Genetics

Spinocerebellar ataxia 7 is caused by expanded trinucleotide repeats (CAG) in the ATXN7 gene (3p21.1-p12) and inherited in an autosomal dominant pattern.  The number of repeats is variable and correlated with severity of disease.  Most patients with 36 or more repeats have significant disease. This disorder is sometimes classified as a progressive cone-rod dystrophy.  It is sometimes referred to as olivopontocerebellar atrophy type III or OPCA3.

This disorder exhibits genetic anticipation especially with paternal transmission as succeeding generations often have earlier onset with more severe and more rapidly progressive disease. This is explained by the fact that younger generations tend to have a larger number of repeats and sometimes the diagnosis is made in children before the disease appears in parents or grandparents.

Spinocerebellar ataxia 1 (164400) is a similar autosomal dominant disorder with many of the same clinical and genetic features.  It is caused by excess CAG repeats on the ATXN1 gene on chromosome 6. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No effective treatment is known for the disease.  Low vision aids and mobility training may be useful in early stages. 

References
Article Title: 

Galactokinase Deficiency

Clinical Characteristics
Ocular Features: 

This is a considerably more rare disorder of galactose metabolism compared with classic galactosemia (230400).  Both disorders cause cataracts in the neonatal period but the early systemic effects of galactokinase deficiency are less severe.  In the latter disorder, cataracts usually develop later, often during the first decade of life and less commonly during the neonatal period that is characteristic of classic galactosemia.  Galactitol  accumulation causing osmotic changes in the lens accounts for the cataracts and may also be responsible for the development of pseudotumor cerebri found infrequently.  Good dietary control may prevent the formation and progression of cataracts and it has been reported that they may regress as well but only prior to the rupture of cell membranes.

Systemic Features: 

Late complications include abnormalities in mental and/or motor development, dyspraxia, and hypogonadotropic hypogonadism which occur in spite of severe reduction in galactose intake.  Ovarian failure is common.

Genetics

This is an autosomal recessive disorder caused by mutations in the GALK1 gene (17q24) encoding galactokinase.  It is extremely rare but should be considered in any patient with cataracts found within the first two decades of life.  Deficient activity of the galactokinase enzyme can be demonstrated in erythrocytes.

For other disorders of galactose metabolism, see galactosemia (230400) and galactose epimerase deficiency (230350).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Early dietary restriction of non-galactose polycarbohydrates and deficient in lactose may prevent the formation of cataracts or sometimes result in regression.

References
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