Cataracts, Hearing Loss, and Neurodegeneration

Clinical Characteristics
Ocular Features: 

Congenital cataracts are the important ocular feature in this syndrome.

Systemic Features: 

Hearing loss is an important part of this syndrome.  Severe hypomyelination and hypoplasia are seen on MRI.  Marked developmental delay and early death are also seen.  Reduced ceruloplasmin secretion and low serum copper are present.

Genetics

This is an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in SLC33A1 (3q25) encoding an acetylCoA transporter (AT-1).  The defect in hepatic cells results in reduced ceruloplasmin secretion with low serum copper.  Wilson disease (277900), Menkes disease (309400), and aceruloplasminemia (604290), other disorders of copper metabolism, have similar blood findings but due to different mechanisms.

Heterozygous mutations in SLC33A1 result in an autosomal dominant form of spastic paraplegia (SPG42) (612539). No ocular abnormalities have been reported in SPG42 though.

Treatment
Treatment Options: 

No information on treatment has been reported.

References
Article Title: 

Mutations in SLC33A1 Cause a Lethal Autosomal-Recessive Disorder with Congenital Cataracts, Hearing Loss, and Low Serum Copper and Ceruloplasmin

Huppke P, Brendel C, Kalscheuer V, Korenke GC, Marquardt I, Freisinger P, Christodoulou J, Hillebrand M, Pitelet G, Wilson C, Gruber-Sedlmayr U, Ullmann R, Haas S, Elpeleg O, N?ornberg G, N?ornberg P, Dad S, M??ller LB, Kaler SG, G?SSrtner J. Mutations in SLC33A1 Cause a Lethal Autosomal-Recessive Disorder with Congenital Cataracts, Hearing Loss, and Low Serum Copper and Ceruloplasmin. Am J Hum Genet. 2012 Jan 13;90(1):61-8.

PubMed ID: 
22243965

References

Huppke P, Brendel C, Kalscheuer V, Korenke GC, Marquardt I, Freisinger P, Christodoulou J, Hillebrand M, Pitelet G, Wilson C, Gruber-Sedlmayr U, Ullmann R, Haas S, Elpeleg O, N?ornberg G, N?ornberg P, Dad S, M??ller LB, Kaler SG, G?SSrtner J. Mutations in SLC33A1 Cause a Lethal Autosomal-Recessive Disorder with Congenital Cataracts, Hearing Loss, and Low Serum Copper and Ceruloplasmin. Am J Hum Genet. 2012 Jan 13;90(1):61-8.

PubMedID: 22243965