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vascular fluid accumulation
5
.
About 20% of the patients die in the first years of life, particularly
those with the visceral form
8
.
Childhood ataxia-intellectual disability stage
Children have a more static course characterized by hypotonia and ataxia. Motor and speech
development is invariably and often severely impaired. The mental retardation is variable, with an
IQ typically between 40 and 70. The children are usually extrovert and cheerful.
Stroke-like episodes leading to stupor, coma, convulsions and hemiplegia are sometimes
associated with fever, seizure, dehydration or trauma and often recovery occurs in days to weeks
or months.
5,8,9
Ischemic processes and edema with subsequent focal necrosis are possibly related
to these episodes
9
.
Seizures are usually responsive to anti-epileptic drugs
9
.
Retinitis pigmentosa,
myopia and cataract may occur in these children
13
.
Adult stable disability stage
The condition appears to be static in adults, without regression. Patients usually have moderate
mental retardation. Neurologic symptoms include ataxia due to cerebellar hypoplasia and
peripheral neuropathy causing progressive muscle atrophy and weakness, especially of the lower
extremities. Skeletal deformities like kyphosis, scoliosis and pectus excavatum occur as a
consequence of muscle atrophy. Hepatomegaly stabilizes or disappears and renal function is
preserved. Retinitis pigmentosa is predominantly seen in older patients. Central vision may be
preserved, transient.
5
Deep venous thrombosis has been reported in adults, especially in case of
prolonged immobilization, dehydration and/or infection. Female patient have signs of
hypogonadism, whereas male patients appear to have a normal puberty with sometimes testicular
atrophy. Adults with PMM2-CDG have not been reported to reproduce.
5,8,9
Adults are generally socially functioning but can seldom function independently and are often
wheelchair-bound.
8
Diagnosis
PMM deficiency should be considered in any child or adult with unexplained psychomotor
retardation, especially if this is accompanied by suggestive features such as unusual subcutaneous
fat distribution, retracted nipples, feeding problems, failure to thrive and coagulation
abnormalities. A clinical suspicion can be substantiated by isoelectric focusing (IEF) of serum
transferrin. The diagnosis is confirmed by finding decreased PMM activity in leucocytes of
fibroblasts. This diagnosis should be completed by mutational analysis of the PMM2 gene.
8
The
most prevalent mutation is the R141H substitution in a compound heterozygote form.
5,10
Prenatal
testing should only be offered to families with documented PMM deficiency and mutations in
PMM2.
4
For the functional assessment of patients with PMM2-CDG the Nijmegen pediatric CDG rating scale
can be used.
2
Treatment
At present no efficient treatment is available for patients with PMM2-CDG. Despite the promising
finding that adding mannose to patients’ fibroblasts corrected deficient mannose incorporations,
neither oral nor IV mannose supplementation had been proven to be beneficial.
4,5
Management of patients with PMM2-CDG consists of symptom control and treatment of
complications.
5,9
In case of failure to thrive in infants and children nasogastric or gastrotomy tube feeding might be
required, in addition to consultation with a dietician and speech therapist.
Motor, cognitive and speech development should be stimulated by occupational therapy, physical
therapy and speech therapy. While parents may need counselling and support concerning the
widening gap in development between children with PMM2-CDG and unaffected children.