IllnessHomocystinuria, classic; differential diagnosis

NGS +

Homocystinuria is a hereditary disease in which the organism does not process certain amino acids properly. There are several forms of homocystinuria, which differ in their symptoms and genetic causes. The most common form of homocystinuria is characterised by myopia, lens luxations, increased risk of impaired blood clotting and osteoporosis or other skeletal abnormalities. Some affected individuals also experience developmental delays and learning problems. Less common forms of homocystinuria can lead to intellectual deficits, failure to thrive and move, seizures and megaloblastic anaemia. Symptoms of homocystinuria usually develop within the first year of life, although some mildly affected patients may become noticeable later in childhood or not until adulthood. Mutations in the CBS gene cause the classic, most common form of homocystinuria. The CBS gene codes for the cystathionine-beta synthase protein, a critical member in a specific metabolic pathway. Also other amino acids, including methionine, are produced via this pathway. When cystathionine-beta synthase malfunctions, homocysteine accumulates and toxic by-products accumulate in the blood. Some of the excess homocysteine is excreted in the urine. In rare cases, homocystinuria can be caused by mutations in several other genes, such as MTHFR. The mode of inheritance is autosomal recessive. Hereditary diseases that should be considered in the differential diagnosis may follow the autosomal dominant pattern. Although the molecular genetic yield is quite high after appropriate clinical biochemical characterisation, though without really being known in detail, the clinical diagnosis is not refuted by a negative DNA test result.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1524/

• Alias: Cystathionin-beta-Synthase-Mangel
• Alias: Homocystinuria caused by Cystathionine beta-synthase deficiency (CBS)
• Alias: Homocystinurie durch Cystathionin-beta-Synthase-Mangel
• Alias: Homozystinurie, klassische
• Galactosemia (GALT)
• Glycine N-methyltransferase deficiency (GNMT)
• Homocystinuria due to MTHFR deficiency (MTHFR)
• Homocystinuria, B6-responsive and nonresponsive types (CBS)
• Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase (AHCY)
• Hypermethioninemia, persistent, AD, due to methionine adenosyltransferase I/III deficiency (MAT1A)
• Marfan syndrome (FBN1)
• Methionine adenosyltransferase deficiency, AR (MAT1A)
• Methylmalonic aciduria + homocystinuria, cblF type (LMBRD1)
• Sulfite oxidase deficiency (SUOX)
• Thrombosis, hyperhomocysteinemic (CBS)
• Tyrosinemia, type I (FAH)