PMM2 deficiency or PMM2-CDG is a very rare
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
caused by mutations in
PMM2
Phosphomannomutase 2 is an enzyme that in humans is encoded by the ''PMM2'' gene.
Function
Phosphomannomutase 2 catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate. Mannose 1-phosphate is a precursor to GDP-mannose nece ...
. It is an autosomal recessive disorder. A defective copy of the PMM2 gene is the most common cause of a disease called “
congenital disorders of glycosylation
A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defecti ...
” or “PMM2-CDG”. PMM2-CDG is the most common of a growing family of more than 130 extremely rare inherited metabolic disorders. Only about 1000 children and adults have been reported worldwide.
Signs and symptoms
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Failure to thrive (FTT) - Failure to gain weight and grow at the expected rate.
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Cerebellar hypoplasia - Small cerebellum, which is the part of the brain that coordinates movement.
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Liver disease - Elevated liver function tests.
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Pericardial effusion
A pericardial effusion is an abnormal accumulation of fluid in the pericardial cavity. The pericardium is a two-part membrane surrounding the heart: the outer fibrous connective membrane and an inner two-layered serous membrane. The two layers of t ...
- Fluid around the heart.
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Peripheral neuropathy (PN) - Impaired nerve impulse transmission to the legs. Patients do not respond well to reflex tests.
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Strabismus - Crossed eyes, mainly presented as infantile
Esotropia
Esotropia is a form of strabismus in which one or both eyes turns inward. The condition can be constantly present, or occur intermittently, and can give the affected individual a "cross-eyed" appearance. It is the opposite of exotropia and usual ...
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Nystagmus - Involuntary eye movements caused by
Cerebellar ataxia
Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias.
Cerebellar ataxia can occur as a result of many diseases and may present with symptoms ...
.
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Hypotonia
Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...
- Weak muscle tone, commonly known as floppy baby syndrome.
Diagnosis
PMM2 deficiency is diagnosed through genetic sequencing. More than 115 mutations in PMM2 gene have been found to cause this disease.
Treatment
Treatment with mannose powder 1-2g / kg per day results in significant improvement in protein glycosylation after 1 year.
Other treatments involves management of the symptoms that are apparent in each individual, including Physical Therapy to improve core strength and mobility, Occupational Therapy for coordination, Speech Therapy for talking and eating.
References
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Genetic diseases and disorders
Congenital disorders of glycosylation