Tay-Sachs disease: Pseudodeficiency variants in the XXXX gene are not disease-causing. Although a pseudodeficiency variant can cause enzyme results to be in the carrier or indeterminate range, a pseudodeficiency variant does not increase an individual&amp;apos;s risk to have a child with Tay-Sachs disease. (XXXXX, XXXX:XXXXXXX). The standard of care for Tay-Sachs disease carrier detection in all ethnic groups is enzyme (hexosaminidase A) analysis. For maximum sensitivity and specificity, enzyme analysis should be performed in addition to DNA variant analysis (XXXXXXXX, PMID:XXXXXXX).

Beta hemoglobinopathies, includes sickle cell disease and beta thalassemias: Beta hemoglobinopathies, including sickle cell disease and beta thalassemia, are autosomal recessive disorders of red blood cells with variable severity and age of onset. Clinical features of sickle cell disease include chronic hemolytic anemia, pain crises, susceptibility to infection, and organ damage. Features of beta thalassemiatypically include mild to severe anemia, hepatosplenomegaly, and skeletal changes. Carriers of beta thalassemia may have mild anemia. Symptoms of other beta hemoglobinopathies depend on the combination of XXXXXXX gene mutations and can range from mild anemia to severe multi-system disease. (XXXXXX, PMID:XXXXXXX; XXXXX, PMID:XXXXXXX). Treatment is primarily supportive and focuses on prevention of complications and management of symptoms. In cases of severe disease, bone marrow or cord blood transplantation can be curative. (XXXXXX, PMID:XXXXXXX). Carrier detection should combine clinical information, complete blood count, hemoglobin electrophoresis, and DNA testing (XXXXX-XXXXXXX, PMID: XXXXXXX).

Cystic fibrosis: Cystic fibrosis (CF) is an autosomal recessive disease with variable severity and age of onset. Symptoms of classic CF include elevated sweat chloride levels, progressive lung disease, pancreatic insufficiency, and male infertility. Individuals with mild CF may have pancreatic sufficiency. CFTR-related disorders include pancreatitis, bronchiectasis, and isolated male infertility due to congenital absence of the vas deferens. Treatment is primarily dietary and supportive. Genotype-targeted therapies may be available for some individuals. In severely affected individuals, lung transplantation may be indicated. (XXXXXXXXX, PMID:XXXXXXXX).

Sandhoff disease: Sandhoff disease is an autosomal recessive disease with variable severity and age of onset. Onset in infancy is most common with symptoms that typically include progressive neurological deterioration, spasticity, loss of motor and cognitive skills, progressive weakness, blindness, organomegaly, seizures, and cherry-red spot on ophthalmological examination. Treatment is supportive. (XXXXXXXXX, PMID:XXXXXXXXXX; XXXXX, PMID:XXXXXXXXX; XXXXXXXXXX, PMID:XXXXXXXXX).