GNE Myopathy (GNEM)

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GNE Myopathy (GNEM), is a progressive, adult-onset, recessive genetic disorder caused by loss of function mutations in the GNE gene. GNE encodes the enzyme responsible for the committed step in sialic acid biosynthesis.

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Incidence of GNE myopathy is estimated to be between 1 and 6 in a million, but the disease is often not diagnosed (2000 patients definitively diagnosed through genomic sequencing but estimated number of cases is 40,000). Also, carrier frequency is very high in certain populations (e.g., Iranian Jews as high as 1 in 8).

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Lysosomal acid lipase deficiency (LAL-D)

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Lysosomal acid lipase deficiency (LAL-D) is a severe, rare, lysosomal storage disorder caused by recessive loss of function mutations in the Lipase A (LIPA) gene. The LIPA gene encodes a lysosomal enzyme required for the breakdown of triglycerides to free fatty acids and cholesterol esters to cholesterol. Complete loss of gene function causes Wolman Disease, a disease of infancy where patients have an average lifespan of less than 4 months without treatment. Partial loss of function mutations can cause Cholesteryl Ester Storage Disease (CESD), which may present in childhood or adulthood.

 

LAL-D prevalence is estimated at 1:40,00 to 1:800,000, but lowered LIPA function is also a biomarker for non-alcoholic fatty liver disease (NAFLD, affecting 30-40% of the US population) and non-alcoholic steatohepatitis (NASH, affecting 3-12% of US population).

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​Limb-girdle muscular dystrophy type 2I (LGMD2I)

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Limb-girdle muscular dystrophy type 2I (LGMD2I) is a form of limb-girdle muscular dystrophy, which refers to a group of conditions that cause weakness and wasting of the muscles in the arms and legs. It is caused by a defect in the FKRP gene and is inherited in an autosomal recessive manner. The most commonly affected muscles are the proximal muscles (those closest to the body such as the upper arms and thighs). In LGMD2I, specifically, signs and symptoms often develop in late childhood (average age 11.5 years) and may include difficulty running and walking. The symptoms gradually worsen overtime and affected people generally rely on a wheelchair for mobility approximately 23-26 years after onset. There are about 5,000 people in the U.S. that are affected by this disease and more worldwide.