SNP Shot: Genomic Insights

Hypermanganesemia with dystonia is a genetic condition characterized by an abnormally high level of manganese in the body (hypermanganesemia). This excess manganese primarily accumulates in the brain, specifically in areas controlling movement, leading to neurological problems. The primary symptom is dystonia, which involves involuntary, sustained muscle contractions, as well as other uncontrolled movements. There are two recognized types: hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC or type 1) and hypermanganesemia with dystonia 2, distinguished by their different genetic causes and specific clinical features.

In HMDPC (also known as hypermanganesemia with dystonia 1), manganese builds up in the blood, brain, and liver. The condition can manifest either in childhood (early-onset, typically between ages 2 and 15) or in adulthood (adult-onset). Early-onset HMDPC often presents with dystonia affecting the arms and legs, leading to a distinctive, high-stepping "cock-walk gait." Other neurological symptoms in children include tremors, abnormally slow movements (bradykinesia), and slurred speech (dysarthria). Adult-onset HMDPC is typically characterized by parkinsonism, a set of movement-related symptoms including bradykinesia, tremor, muscle stiffness (rigidity), and difficulty maintaining balance (postural instability).

People with HMDPC also have an elevated red blood cell count (polycythemia) and low iron stores. Additional features may include an enlarged liver (hepatomegaly) caused by manganese accumulation, liver scarring (fibrosis), and ultimately, irreversible liver damage (cirrhosis).

In hypermanganesemia with dystonia 2, manganese accumulates in the blood and brain. Symptoms usually appear between 6 months and 3 years of age. Development of motor skills may be delayed, or previously acquired skills may be lost. Dystonia can affect any part of the body and tends to worsen over time. By late childhood, the persistent muscle contractions frequently result in permanently bent joints (contractures) and the inability to walk without assistance. Some individuals may also develop scoliosis, an abnormal curvature of the spine. Neurological issues similar to those seen in HMDPC, such as tremor, bradykinesia, parkinsonism, and dysarthria, can also occur in hypermanganesemia with dystonia 2. Unlike HMDPC, polycythemia and liver problems are not features of hypermanganesemia with dystonia 2.

Inheritance:

Hypermanganesemia with dystonia is inherited in an autosomal recessive manner. This means that to develop the condition, an individual must inherit a mutated copy of either the SLC30A10 or SLC39A14 gene from each parent. The parents, who each carry only one copy of the mutated gene, are usually unaffected and do not exhibit any signs or symptoms of the disorder.