Diagnosis and high incidence of hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome in northern Saskatchewan

@article{Sokoro2010DiagnosisAH,
  title={Diagnosis and high incidence of hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome in northern Saskatchewan},
  author={AbdulRazaq Sokoro and Joyce Lepage and Nick A. Antonishyn and Ryan R. McDonald and Cheryl Rockman‐Greenberg and James Irvine and Denis C. Lehotay},
  journal={Journal of Inherited Metabolic Disease},
  year={2010},
  volume={33},
  pages={275-281}
}
Mutations in the SLC25A15 gene, encoding the human inner mitochondrial membrane ornithine transporter, are thought to be responsible for hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome, a rare autosomal recessive condition. HHH syndrome has been detected in several small, isolated communities in northern Saskatchewan (SK). To determine the incidence of HHH syndrome in these communities, a PCR method was set up to detect F188Δ, the common French-Canadian mutation. Neonatal… 
Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Syndrome Causing Severe Neonatal Hyperammonemia.
TLDR
The first confirmed instance of HHH syndrome in a premature infant with severe hyperammonemia is reported, highlighting the importance of considering HHH in the differential diagnosis for neonatal hyper ammonemia.
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.
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.
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.
Milder Form of Urea Cycle Defect Revisited: Report and Review of Hyperornithinaemia-Hyperammonaemia-Homocitrullinuria (HHH) Syndrome Diagnosed in a Teenage Girl Presenting with Recurrent Encephalopathy.
TLDR
An additional case of a girl of Indian descent, who presented with recurrent episodes of altered mental state in association with febrile illnesses and was subsequently diagnosed with HHH syndrome is described.
The Association between SLC25A15 Gene Polymorphisms and Hyperornithinemia-hyperammonemia-homocitrullinuria Syndrome: Using In Silico Analysis
TLDR
This study is the first in silico analysis of SLC25A15 using a selection of bioinformatics tools to detect functional and structural effects of deleterious SNPs.
Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease‐causing variants
TLDR
The Ashkenazi Jewish (AJ) population has an increased risk for a variety of recessive diseases due to historical founder effects and genetic drift, and the carrier frequencies of 85 pathogenic variants causative of 29 recessive conditions in the AJ population are assessed.
Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing
TLDR
The occurrence of UCDs in India and the spectrum that may be different from the rest of the world is reported and genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies.
Newborn Screening for Inborn Errors of Metabolism
TLDR
Newborn screening was first applied to the detection of phenylketonuria by a bacterial inhibition assay pioneered in 1961 by Guthrie, and since then other disorders covered in some screening programmes have included congenital adrenal hyperplasia, the galactosaemias, cystic fibrosis, biotinidase deficiency, glucose-6-phosphate dehydrogenase deficiency and many others.
...
...

References

SHOWING 1-10 OF 29 REFERENCES
Phenotypic variability among patients with hyperornithinaemia–hyperammonaemia–homocitrullinuria syndrome homozygous for the delF188 mutation in SLC25A15
TLDR
Long-term follow-up showed that variable intellectual impairment and lower limb spasticity often occur, together or separately, with no obvious relationship to age at diagnosis and compliance with treatment, and the need to better understand the pathophysiology of HHH is emphasised.
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
HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation
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.
Identification of novel mutations in the SLC25A15 gene in hyperornithinemia‐hyperammonemia‐homocitrullinuria (HHH) syndrome: A clinical, molecular, and functional study
TLDR
Although patient metabolic alterations responded well to low‐protein therapy, predictions concerning the long‐term evolution of HHH syndrome remain uncertain and the preference for a hepatic rather than a neurological presentation at onset continues to elude us.
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.
Three novel mutations (G27E, insAAC, R179X) in the ORNT1 gene of Japanese patients with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome
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).
Episodic hyperammonemia in adult siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome.
TLDR
During therapy with citrulline and phenylbutyrate sodium, plasma ornithine levels increased in both patients, while plasma levels of glutamine and alanine decreased to normal, and no recurrent neurologic dysfunction has occurred during a follow-up period of 20 months.
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
Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X
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.
...
...