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Congenital Disorder of Glycosylation, Type Ij

OMIM ID:

autosomal recessive

Congenital Disorder of Glycosylation, Type Ij

Alternate Names

CDG-Ij
CDG-1j
DPAGT1-CDG (CDG-lj)

Defective Genes

DPAGT1

Clinical Characteristics

Ocular Features

Bilateral cataracts are present at birth.  Nystagmus, strabismus, and long eyelashes have been reported.

Systemic Features

This is a disorder of glycosylation important to the formation of glycoproteins and glycolipids.  Neurological signs such as tremor, clonus, and muscle fasiculations may be seen soon after birth.  Other neurological abnormalities eventually include psychomotor retardation, seizures, mental retardation, hyperexcitabilty, and ataxia.  Failure to thrive and feeding difficulties are evident early.  Progressive microcephaly is a feature.  Liver dysfunction can lead to coagulopathy and hypoproteinemia with hepatomegaly is sometimes present.  Some patients have facial anomalies, inverted nipples, and subcutaneous fat pads.  The MRI may show areas of brain atrophy, ischemia, and focal necrosis.

Longevity is limited with 2 of 3 reported patients dying within 2 years of life.

Genetics

Inheritance

This is a rare autosomal recessive disorder resulting from mutations in DPAGT1 (11q23.3) resulting in defective N-glycosylation.  There are numerous other types of glycosylation defects with variations in the clinical manifestations.

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

Treatment consists of fluid and caloric intake management.  Hypoproteinemia and coagulation defects may respond to oral mannose administration.

Selected Resources

Web Resources

Publications

Displaying 1 - 2 of 2

Congenital disorder of glycosylation type Ij (CDG-Ij, DPAGT1-CDG): Extending the clinical and molecular spectrum of a rare disease

PubMedID: 22304930

Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) Causes a Novel Congenital Disorder of Glycosylation Type Ij

PubMedID: 12872255