Isolated sulphite oxidase deficiency mimics the features of hypoxic ischaemic encephalopathy

Hobson, Emma Elizabeth; Thomas, Sumesh; Crofton, Patricia M.; Murray, Alison; Dean, John; Lloyd, D. J.

doi:10.1007/s00431-005-1729-5

Cited by 39 publications

(29 citation statements)

References 14 publications

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“…In cattle the main predilection site of Moco-deficiency is the developing bone. Even though bone malformations are not common signs of Moco-deficiency in human and mice, rarely microcephaly and a prominent forehead are observed in patients with Moco- [25] and SOD-deficiency [26]. …”

Section: Discussionmentioning

confidence: 99%

Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1)

2011

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BackgroundArachnomelia syndrome is an autosomal recessive inherited disease in cattle. Affected calves die around birth and show malformations of the skeleton mainly affecting the legs, the spinal column and the skull. A number of arachnomelia syndrome affected Simmental calves were recently detected by a surveillance system of anomalies with a peak of more than 120 recorded cases in the year 2006. The causative mutation was previously mapped to a 9 cM-region on bovine chromosome 23. We herein report the fine-mapping and identification of the gene causing arachnomelia syndrome in Simmental cattle.ResultsBy using a dense set of markers, the arachnomelia syndrome linked region could be refined to 1.5 cM harbouring three protein coding genes. Comparative sequencing of these genes revealed a two-bp-deletion in the bovine MOCS1 gene resulting in a frame-shift and a premature termination codon. We genotyped affected calves and their ancestors and found that all affected were homozygous for the deletion whereas all carriers were heterozygous. Furthermore, cattle from the same population, but not directly related to known carriers mostly showed the wild type genotype.ConclusionsMOCS1 encodes two proteins that are involved in the first synthesis step of molybdenum cofactor. A non functional sulfite-oxydase, one of the enzymes requiring molybdenum cofactor, leads to a similar pathology in Brown Swiss cattle. In combination the perfect association of the mutation with the phenotype and the obvious disruption of protein translation provide strong evidence for the causality of the MOCS1 mutation. Our results are the first example for an oligogenic lethal inherited disease in cattle. Furthermore, they show the potential involvement of sulfite metabolism in aberrant bone development.

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Section: Discussionmentioning

confidence: 99%

Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1)

2011

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“…Neurologic development is typically arrested at the level of brain stem function with no acquired developmental achievements 2 . Our patient's constellation of symptoms were representative of the classic phenotype and included progressive microcephaly, spasticity, severe developmental delay, cystic MRI changes and premature death 4,6,10 . Patients with longer survival often develop ectopia lentis.…”

Section: Discussionmentioning

confidence: 84%

“…Since then, ISOD remains rare and infrequently reported in the medical literature. This might be due to underdiagnosis, since the neuropathology and clinical presentation mimics severe perinatal asphyxia and might be mistaken for hypoxic ischemic encephalopathy (HIE) 4 . Despite the discovery of the genetic defect, improved biochemical diagnosis and better understanding of the pathophysiology, there is currently no curative treatment.…”

mentioning

confidence: 99%

Isolated Sulfite Oxidase Deficiency: Response to Dietary Treatment in a Patient with Severe Neonatal Presentation

Boyer

Sowa

Wang

et al. 2019

J. inborn errors metab. screen.

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Isolated sulfite oxidase deficiency (ISOD) is a devastating, neurometabolic disorder caused by mutations in the SUOX gene necessary for the final step in the sulfur-containing amino acid catabolic pathway. Patients classically present in the neonatal period with neurologic manifestations. Biochemical findings include elevated sulfocysteine, low cystine and undetectable homocysteine with normal uric acid levels. Other associated biochemical markers include elevated plasma alpha-aminoadipic semialdehyde and piperideine-6-carboxylic acid. We report a patient with classic neonatal onset ISOD (refractory seizures, hypertonicity, brain abnormalities, pathogenic SUOX mutations). Her clinical course was marked by extreme irritability, prompting the use of a low methionine and cystine diet to decrease toxic metabolites thought to be contributing to her symptoms. Biochemical markers and extreme irritability improved with dietary treatment (methionine=30mg/kg/day). She died of sepsis in early infancy, precluding long term follow-up. This case reviews the potential benefits and limitations of diet therapy in this rare disorder.

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“…JBR-BTR, 2014, 97: 113-114. the basal ganglia, resulting in a multicystic encephalomalacia similar to that found in the context of severe perinatal hypoxic-ischemic injury and twin-to-twin transfusion syndrome (4,5). The clinical context and laboratory investigations are therefore crucial to make the diagnosis.…”

Section: Discussionmentioning

confidence: 93%

Sulfite oxidase deficiency in a newborn

Meylaerts

et al. 2014

Journal of the Belgian Society of Radiology

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A two-day-old newborn girl presented with intermittent episodes of hypertonia and hypotonia, increasing in frequency and intensity. Her parents were distant cousins , and her two sisters showed a normal development after a normal pregnancy. On admission, an EEG combined with video recording showed no focal epileptic activity during repeated short contractions in both arms and/ or limbs. Seven days later, repeat EEG showed diffusely slowed monomorphic trace of rather low voltage, but again without epileptic characteristics. Brain ultrasound, performed on admission, revealed hypoplasia of the corpus callosum, enlarged lateral ventricles, and cystic formations in the white matter. MRI, performed at age 3 days, confirmed the hypoplasia of the corpus callosum found on ultrasound and showed a diffuse cystic degeneration of the supratentorial white matter, mainly involving the frontoparietal regions (Fig. 1).The subsequent diagnostic workup was based on a differential diagnosis between a possible metabolic disease and hypoxic-ischemic-related mulitcystic encephalopathy. Biochemical examinations revealed undetectable homocysteine plasma levels (0 mol/L, reference value: 15-100 micromol/L) in two separate occasions. Analysis of freshly catheterized urine was positive for sulphite (+/-40 mg/L), and showed an increased S-sulfocysteïne and taurine. A normal value of uric acid was measured in the plasma (4.6 mg/dL, reference 2.0 to 5.5 mg/dL), and there were no elevated urinary levels of xanthine (8 mmol/mol creat., reference value ≤ 66 mmol/mol creat.) or DiscussionSulphite oxidase is a mitochondrial enzyme that plays a role in the oxidation of sulfite to sulfate, which is the final step in the metabolism of sulfur-containing amino acids (methionine, homocysteine) (1). With this step, two electrons are released, and these are mediated by cytochrome c to the electron transport chain, enabling the production of ATP (oxidative phosphorylation). Molybdenum is a necessary co-factor for the hypoxanthine (≤ 99 mmol/mol creat.). The latter measurements ruled out molybdenum cofactor deficiency and a diagnosis of isolated sulfite oxidase deficiency was established. -BTR, 2014, 97: 113-114. JBR Sulfite oxiDaSe DefiCienCy in a newborn

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Isolated sulphite oxidase deficiency mimics the features of hypoxic ischaemic encephalopathy

Cited by 39 publications

References 14 publications

Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1)

Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1)

Isolated Sulfite Oxidase Deficiency: Response to Dietary Treatment in a Patient with Severe Neonatal Presentation

Sulfite oxidase deficiency in a newborn

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