Ornithine translocase deficiency – SLC25A15 gene.
Ornithine translocase deficiency, also known as hyperornithinemia-hyperamonemia-homocitrulinuria syndrome or triple H syndrome, is a hereditary process of varying severity that causes accumulation of ammonia and other substances in the blood.
Signs and symptoms related to this process may vary among affected individuals and include lethargy, lack of appetite, vomiting, breathing and poorly controlled temperature; unusual seizures or body movements; intellectual disability; and developmental delay. Signs related to ornithine translocase deficiency, particularly in cases of late onset, may include episodes of vomiting, lethargy, ataxia, vision problems, encephalopathy, developmental delay, learning problems and spasticity. In addition, affected individuals may have chronic liver problems and mild abnormal bleeding. Ornithine translocase deficiency varies widely in the age of onset. Late-onset forms are usually less severe than the infantile form.
This process is due to mutations in the SLC25A15 gene (solute carrier family 25 member 15), located on the long arm of chromosome 13 (13q14.11), which encodes the mitochondrial ornithine transporter 1. This protein participates in the cycle of urea, through which excess nitrogen is removed to prevent it from accumulating in the form of ammonia. The mitochondrial ornithine transporter 1 transports ornithine through the inner membrane of the mitochondria to the mitochondrial matrix, where it participates in the urea cycle.
At least 35 mutations have been identified in the SLC25A15 gene that lead to the development of ornithine translocase deficiency. The most frequent mutation eliminates the amino acid phenylalanine at position 188 (Phe188del or F188del). Another frequent mutation replaces the amino acid arginine with a premature stop signal in the protein coding (Arg179Ter or R179X). Mutations in the SLC25A15 gene result in the synthesis of a mitochondrial ornithine 1 transporter with reduced or absent function. As a consequence, the transport of ornithine is affected, which alters the urea cycle resulting in an accumulation of nitrogen in the form of ammonia in the blood.
This disease is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we detect mutations associated with Ornithine translocase deficiency, by means of complete PCR amplification of exons of the SLC25A15 gene, and subsequent sequencing.
Recommended samples: blood taken with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).