Further oxidation of this substrate by the fatty alcohol:nicotinamide-adenine dinucleotide oxidoreductase (FAO) enzyme complex, in which one component, ALDH3A2, is known to be mutated in Sjögren-Larsson syndrome (characterized by ichthyosis and spastic paraplegia), would lead to 20-carboxy-(R)-trioxilin A3.
PCH9 is caused by biallelic variants in AMPD2 encoding adenosine monophosphate deaminase 2; however, a homozygous AMPD2 frameshift variant has recently been reported in two family members with spastic paraplegia type 63 (SPG63).
The cohort consists of three families with spastic paraplegia type 47 (AP4B1) with a common mutation in two families, a family with spastic paraplegia type 50 (AP4M1), and two male siblings with X-linked spastic paraplegia 2 (PLP1).
The cohort consists of three families with spastic paraplegia type 47 (AP4B1) with a common mutation in two families, a family with spastic paraplegia type 50 (AP4M1), and two male siblings with X-linked spastic paraplegia 2 (PLP1).
Here we characterize three independent fibroblast lines derived from skin biopsies of patients harbouring nonsense mutations in AP5Z1 and presenting with spastic paraplegia accompanied by neuropathy, parkinsonism and/or cognitive impairment.
In contrast to other urea cycle defects, arginase 1 deficiency usually does not cause catastrophic neonatal hyperammonemia but rather presents with progressive neurological symptoms including seizures and spastic paraplegia in the first years of life and hepatic pathology, such as neonatal cholestasis, acute liver failure, or liver fibrosis.