PMM2 deficiency

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Obesity, Sleep & Internal medicine
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PMM2 deficiency
Synonyms	Congenital disorder of glycosylation type Ia (CDG-Ia)
Pronounce
Specialty	Medical genetics
Symptoms	Developmental delay, hypotonia, ataxia, peripheral neuropathy
Complications	N/A
Onset	Infancy
Duration	Lifelong
Types
Causes	Mutations in the PMM2 gene
Risks
Diagnosis	Genetic testing, biochemical analysis
Differential diagnosis	Other congenital disorders of glycosylation
Prevention
Treatment	Supportive care, physical therapy
Medication
Prognosis	Variable, depends on severity
Frequency	Estimated 1 in 20,000 to 50,000 live births
Deaths

PMM2 deficiency, also known as Congenital Disorder of Glycosylation Type Ia (CDG-Ia) or Phosphomannomutase 2 deficiency, is a rare, inherited metabolic disorder that affects the body's ability to properly attach sugars to proteins and lipids, a process known as glycosylation. This condition is part of a larger group of diseases known as Congenital Disorders of Glycosylation (CDGs), which are caused by defects in the enzymes involved in glycosylation pathways.

Symptoms and Signs

The symptoms of PMM2 deficiency can vary widely among affected individuals but typically include severe developmental delay, intellectual disability, failure to thrive, and various problems with the nervous system, liver, intestines, and coagulation. Affected infants often present with inverted nipples and abnormal fat distribution. Other common features include strabismus, hepatomegaly, peripheral neuropathy, and ataxia. Due to its impact on multiple body systems, PMM2 deficiency is considered a multisystem disorder.

Genetics

PMM2 deficiency is caused by mutations in the PMM2 gene, which encodes the enzyme phosphomannomutase 2. This enzyme is crucial for the early steps of the glycosylation pathway. The disorder is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected. Parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Diagnosis

Diagnosis of PMM2 deficiency involves a combination of clinical evaluation and laboratory tests. Screening tests may include transferrin isoform analysis, which can detect abnormal glycosylation patterns. Definitive diagnosis is usually achieved through genetic testing to identify mutations in the PMM2 gene.

Treatment and Management

There is currently no cure for PMM2 deficiency, and treatment is supportive and symptomatic. Management may include physical therapy, occupational therapy, and speech therapy to help with developmental delays and motor skills. Nutritional support is also important, and some individuals may require feeding tubes. Regular monitoring by a multidisciplinary team of healthcare providers is essential to address the various aspects of the disorder.

Prognosis

The prognosis for individuals with PMM2 deficiency varies depending on the severity of symptoms and the extent of organ involvement. Early intervention and supportive care can improve the quality of life for many affected individuals. However, the disorder can be life-threatening, especially in severe cases or when not properly managed.

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