In fetal development, maternal glucose transferred to the fetus prevents hypoglycemia, but the storage of glucose as glycogen in the liver leads to hepatomegaly. There is no evidence that this hepatomegaly presents any risk to proper fetal development. Hepatomegaly in GSD type I generally occurs without sympathetic enlargement of the spleen. GSD Ib patients may present with splenomegaly, but this is connected to the use of filgrastim to treat neutropenia in this subtype, not comorbid hepatomegaly. Hepatomegaly will persist to some degree throughout life, often causing the abdomen to protrude, and in severe cases may be palpable at or below the navel. In GSD-related non-alcoholic fatty liver disease, hepatic function is usually spared, with liver enzymes and bilirubin remaining within the normal range. However, liver function may be affected by other hepatic complications in adulthood, including the development of hepatic adenomas. Hepatic adenomas
The specific etiology of hepatic adenomas in GSD I remains unknown, despite ongoing research. The typical GSD I patient presenting with at least one adenoma is an adult, though lesions have been observed in patients as young as fourteen. Adenomas, composed of heterogeneous neoplasms, may occur individually or in multiples. Estimates on the rate of conversion of a hepatocellular adenoma into hepatocellular carcinoma in GSD I range from 0% to 11%, with the latter figure representing more recent research. One reason for the increasing estimate is the growing population of GSD I patients surviving into adulthood, when most adenomas develop.
Symptoms of OAT deficiency are progressive, and between the ages of 45 and 65, most affected individuals are almost completely blind.In some cases, affected individuals will present in the neonatal period with disease that closely mimics a classic urea cycle defect, such as ornithine transcarbamylase deficiency, as the block in ornithine metabolism leads to secondary dysfunction of the urea cycle. These individuals present with hyperammonemia, poor feeding, failure to thrive and increased excretion of orotic acid. Genetics
OAT deficiency is inherited in an autosomal recessive manner, meaning an affected individual must inherit a mutated allele from both parents. The enzyme, ornithine aminotransferase is coded for by the gene OAT, located at 10q26. OAT deficiency has an increased incidence in Finland, and this population has a common mutation accounting for more than 85% of mutant alleles in this population. It has not been described in any other populations. Diagnosis
Upon clinical suspicion, diagnostic testing will often consist of measurement of amino acid concentrations in plasma, in search of a significantly elevated ornithine concentration. Measurement of urine amino acid concentrations is sometimes necessary, particularly in neonatal onset cases to identify the presence or absence of homocitrulline for ruling out ornithine translocase deficiency (hyperornithinemia, hyperammonemia, homocitrullinuria syndrome, HHH syndrome). Ornithine concentrations can be an unreliable indicator in the newborn period, thus newborn screening may not detect this condition, even if ornithine is included in the screening panel.