OMIM ID:
Congenital Disorder of Glycosylation, Type Ia
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Strabismus, roving eye movements (and nystagmus), and visual inattention are found in nearly all patients. Esotropia with defective abduction seems to be the most common oculomotor finding and may be present at birth. Cataracts, ocular colobomas, oculomotor apraxia, disc pallor, and glaucoma have also been reported. Vision is always subnormal. Reports of ocular disease before modern genotyping are not specific to the subtypes of CDG I now recognized.
This is a congenital, progressive disorder of photoreceptor degeneration with a later onset of progressive pigmentary retinopathy. It is described in some cases as a typical retinitis pigmentosa. The ERG is abnormal in all patients even if the pigmentary pattern is atypical for RP. Rod responses are usually absent while the cone b-wave implicit time is delayed. The degree of photoreceptor damage is variable, however. Extended retinal function among younger patients suggest that the ‘on-pathway’ evolving synapses in the outer plexiform layer among photoreceptors, bipolar cells, and horizontal cells is severely dysfunctional.
Systemic Features
This is a multisystem disorder, often diagnosed in the neonatal period by the presence of severe encephalopathy with hypotonia, hyporeflexia, and poor feeding. Failure to thrive, marked psychomotor retardation, delayed development, growth retardation, and ataxia become evident later in those who survive. Cerebellar and brainstem atrophy with a peripheral neuropathy can be demonstrated during late childhood. Some older patients have a milder disease, often with muscle atrophy and skeletal deformities such as kyphoscoliosis and a fusiform appearance of the digits. Maldistribution of subcutaneous tissue is often seen resulting in some dysmorphism, especially of the face. Hypogonadism and enlargement of the labia majora are commonly present. Some patients have evidence of hepatic and cardiac dysfunction which together with severe infections are responsible for a 20% mortality rate in the first year of life.
Genetics
Inheritance
This is one of a group of genetically (and clinically) heterogeneous autosomal recessive conditions caused by gene mutations that result in enzymatic defects in the synthesis and processing of oligosaccharides onto glycoproteins. This type (Ia) is the most common. The mutation lies in the PMM2 gene (16p13.2).
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.
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.