Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia.
Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.
Sass
Jörn Oliver
JO
Labor für Klinische Biochemie und Stoffwechsel, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg, Freiburg, Germany. joern.oliver.sass@uniklinik-freiburg.de
Gunduz
Aysegul
A
Araujo Rodrigues Funayama
Carolina
C
Korkmaz
Baris
B
Dantas Pinto
Kylvia Giselle
KG
Tuysuz
Beyhan
B
Yanasse Dos Santos
Letícia
L
Taskiran
Emine
E
de Fátima Turcato
Marlene
M
Lam
Ching-Wan
CW
Reiss
Jochen
J
Walter
Melanie
M
Yalcinkaya
Cengiz
C
Camelo Junior
José Simon
JS
D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics; D001938:Brazil; D003067:Coenzymes / Q000172:deficiency* / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004678:Encephalomalacia / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008667:Metalloproteins / Q000172:deficiency* / Q000235:genetics; D000090006:Molybdenum Cofactors; D011621:Pteridines; D012640:Seizures / Q000150:complications / Q000209:etiology*; D050876:Sulfite Oxidase / Q000172:deficiency* / Q000235:genetics; D014421:Turkey
D003067:Coenzymes; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D011621:Pteridines; D050876:Sulfite Oxidase; C022261:molybdopterin