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Methylmalonic acidemia has amino and organic acid profiles similar to propionic acidemia, but also has very high levels of methylmalonic acid and higher lactic acid levels than propionic acidemia due to inhibition of pyruvate carboxylase. Some patients with methylmalonic acidemia also show homocystinuria, hypomethioninemia, and cystothioninuria.
Propionic and methylmalonic acidemias may produce pancytopenia. The diagnosis of propionic and methylmalonic acidemias are established by finding decreased activity of propionyl-CoA carboxylase in leukocytes or cultured skin fibroblasts and decreased activity of methylmalonyl-CoA mutase in liver and cultured fibroblasts. A neutral pH does not exclude propionic and methylmalonic acidemias since the lactic acid elevation that occurs with these organic acidemias is usually in the 3 to 6 mmol/L range and a neutral pH is maintained until levels of lactic acids are at least 5 mmol/L.
Treatment of propionic and methylmalonic acidemias consists of metabolic support, elimination of protein intake, removal of ammonia, and carnitine supplementation. In addition, neonates with propionic acidemia should be given biotin and those with methylmalonic acidemia should be given vitamin B12. Propionyl-CoA carboxylase deficiency also occurs in multiple carboxylase deficiency.

Sulfite oxidase deficiency and molybdenum cofactor deficiency
Sulfite oxidase deficiency may occur as an isolated enzyme defect or in association with xanthine dehydrogenase and aldehyde oxidase deficiencies in molybdenum cofactor deficiency (Figure 77.1).

Figure 77.1. Methionine and xanthine pathways showing different enzymatic blocks. 1: Sulfite oxidase; 2: aldehyde oxidase 3: xanthine dehydrogenase; *molybdenum cofactor (molybdopterin). High levels of sulfite are apparently toxic to the brain.

Sulfite oxidase deficiency is tentatively diagnosed by an elevated sulfite, taurine, thiosulfate and sulfocysteine levels in the urine and blood. In molybdenum cofactor deficiency, in addition to the accumulations produced by the deficiency of sulfite oxidase, the deficiencies of xanthine dehydrogenase and aldehyde oxidase produce decreased uric acid in the blood. Neonates with sulfite oxidase deficiency or molybdenum cofactor deficiency may have mild facial dysmorphism (large head, upturned nose, telecanthus, cleft palate, and broad nasal bridge), enophthalmus, and lens dislocation. These conditions should be considered in neonates with the previously described features or in neonates with a clinical picture characteristic of hypoxic ischemic encephalopathy without history of asphyxia. MRI findings may suggest these disorder (Figure 77.2).


Figure 77.2 MRI findings in a neonaate with isolated sulfite oxidase deficiency. A: MRI at 5 days of age demonstrating bilateral cerebral white matter and bilateral parietal and occipital gray matter edema; B: MRI at 12 days of age demonstrating decreased signal intensity at the gray matter-white matter junction; C: MRI at 31 days of age demonstrating extensive cystic cavities and enlarged ventricles.

Sulfite oxidase activity and xantine dehydrogenase activity can be assessed in cultured fibroblasts.


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Ogier, 1990 Ozand, 1991a Ozand, 1991b Robinson, 1989 Volpe, 1995 Lombeck, 1990 Dublin, 2002