Phenotypic variability among patients with hyperornithinaemia–hyperammonaemia–homocitrullinuria syndrome homozygous for the delF188 mutation in SLC25A15

@article{Debray2008PhenotypicVA,
  title={Phenotypic variability among patients with hyperornithinaemia–hyperammonaemia–homocitrullinuria syndrome homozygous for the delF188 mutation in SLC25A15},
  author={François Guillaume Debray and Marie Lambert and B. Lemieux and Jean-François Soucy and Régen Drouin and Daphna Fenyves and J Dub{\'e} and Bruno Maranda and R Laframboise and Grant A Mitchell},
  journal={Journal of Medical Genetics},
  year={2008},
  volume={45},
  pages={759 - 764}
}
Background: Hyperornithinaemia–hyperammonaemia–homocitrullinuria (HHH) syndrome (OMIM 238970) is caused by impaired ornithine transport across the inner mitochondrial membrane due to mutations in SLC25A15. To date, 22 different mutations of the SLC25A15 gene have been described in 49 patients belonging to 31 unrelated families. Objective: To further delineate the phenotypic spectrum of HHH syndrome from a description of a genetically homogeneous cohort of patients and identify prognostic… 
A Novel Mutation of ORNT1 Detected in a Hyperornithinemia–Hyperammonemia–Homocitrullinuria Syndrome Child by Clinical Whole-Exome Sequencing
TLDR
A compound heterozygous mutation in SLC25A15 from a 2-year-old girl who presented with neurological alterations and hepatic failure is reported, which identified mutations that are predicted to result in the loss of function of ORNT1.
Immune Alterations in a Patient With Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome: A Case Report
TLDR
This study has identified two non-previously described mutations in the SLC25A15 gene underlying the HHH syndrome and reported for the first time functional and phenotypic immunologic alterations in this rare inborn error of metabolism that would render the patient immunocompromised.
Adult-onset presentation of a hyperornithinemia-hyperammonemia-homocitrullinuria patient without prior history of neurological complications.
TLDR
This is the first reported case of an adult-onset HHH syndrome presentation without a prior history of neurological or cognitive deficiency and additional factors such as gene redundancy, environmental, and epigenetic factors may have contributed to the delay in onset of presentation and lack of any previous symptoms.
Diagnosis and high incidence of hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome in northern Saskatchewan
TLDR
It was determined that ornithine levels, by tandem mass spectrometry, were not abnormal in newborns with F188Δ mutation, carriers and normals, and that newborn screening for HHH Syndrome in this high risk population is only possible by detection of the mutant allele using DNA analysis.
The hyperornithinemia–hyperammonemia-homocitrullinuria syndrome
TLDR
The clinical phenotype of HHH syndrome is extremely variable and its severity does not correlate with the genotype or with recorded ammonium/ornithine plasma levels, suggesting the need for a better understanding of the still unsolved pathophysiology of the disease.
Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome: a treatable genetic liver disease warranting urgent diagnosis.
TLDR
Optimal management of these two patients relied on the concerted efforts of a multidisciplinary team and illustrates the importance of an expanded newborn screening service for early detection and treatment of inherited metabolic diseases.
Late onset hyperornithinemia-hyperammonemia-homocitrullinuria syndrome - how web searching by the family solved unexplained unconsciousness: a case report
TLDR
The case emphasizes the importance of taking rare metabolic genetic disorders into consideration in patients with prolonged unexplained unconsciousness, and underdiagnosed hyperammonemia and recurrence of cerebral edema.
Long-term follow-up of four patients affected by HHH syndrome.
Successful liver transplantation in hyperornithinemia‐hyperammonemia‐homocitrullinuria syndrome: Case report
TLDR
This first case of liver transplantation in HHH syndrome demonstrates that this procedure is a therapeutic option for HHH patients with difficult metabolic control.
Title Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome : a treatable genetic liver disease warranting urgent diagnosis
TLDR
The first two cases in Hong Kong Chinese, who were compound heterozygous siblings for c.535C>T (p.Arg179*) and c.815C>(p.Thr272Ile) in the SLC25A15 gene, show the importance of an expanded newborn screening service for early detection and treatment of inherited metabolic diseases.
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TLDR
A protein-restricted diet and arginine supplementation were immediately started, with a rapid improvement of the patient’s neurological conditions and normalization of liver function tests and blood ammonia, and the diagnosis of HHH syndrome was made.
Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome (HHH) Presenting With Acute Fulminant Hepatic Failure
We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and
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TLDR
This study confirms that defects in the ORNT1 gene cause the HHH syndrome and that the genetic basis in Japanese patients is heterogeneous, and reports three novel mutations in the mitochondrial ornithine transporter gene (ORNT1).
Clinical and Functional Characterization of a Human ORNT1 Mutation (T32R) in the Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) Syndrome
TLDR
Observations suggest that the ORNT1 genotype cannot predict the phenotype of HHH patients, but factors such as redundant transporters and mitochondrial lineage may contribute to the neuropathophysiology of H HH patients.
Seven novel mutations in the ORNT1 gene (SLC25A15) in patients with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome
Eight unrelated Italian patients with the hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome were analyzed for mutations in the ORNT1 gene. Seven novel mutations were identified
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TLDR
A new patient with HHH syndrome is reported, a 52-year-old woman, who had the typical clinical features, except for an absence of mental retardation, suggesting that this is a common mutation in Japanese patients with H HH syndrome.
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