ATYPICAL HEMOLYTIC-UREMIC SYNDROME DUE TO AN INTRACELLULAR ABNORMALITY IN VITAMIN-B12 METABOLISM

Hemolytic uremic syndrome is exceedingly rare during the first few wee ks after birth. Five cases in neonates with an inherited group Cb1C in tracellular vitamin B12 abnormality comparable to that in four previou sly reported cases are described herein. All five patients developed f eeding difficulties, inadequate weight gain, hypotonia, and lethargy w ithin two weeks of birth. Hemolytic uremic syndrome occurred between 2 8 and 90 days of age, with severe hemolytic anemia, schizocytosis, thr ombocytopenia (7/9), proteinuria, hematuria, renal failure (8), and ar terial hypertension (4/9). All patients had unusual clinical and labor atory tests findings including severe acidosis (8 documented cases), l eukoneutropenia (6/9), liver failure (7/8), gastrointestinal bleeding and diarrhea (6/8), respiratory failure due to interstitial pneumonia (6/8), heart failure (3/5), hypotonia and lethargy (7/7), coma (n=2), seizures (n=1), and hydrocephalus (n=2). Pigmentary retinitis was foun d in three of the five patients who underwent ophthalmologic evaluatio n. The diagnosis of group Cb1C vitamin B12 metabolic deficiency was es tablished based on very high plasma levels of homocysteine and methylm alonic acid, very low plasma levels of methionine, and very high urina ry excretions of homocysteine and methylmalonic acid. There were eight deaths. of which sis were due to multiorgan failure and two to perman ent neurologic damage. The most recently diagnosed patient was doing w ell with no sequellae at age 2 years months, this is the only patient who was treated with hydroxycobalamine, folinic acid, and betaine with in 24 hours of onset or thr hemolytic uremic syndrome. Histologic stud ies disclosed glomerular and arteriolar thrombi and;or thrombotic glom erular microangiopathy in the renal parenchyma: thrombi in pulmonary a rterioles and small arteries, with severe interstitial pneumonia; comp lete atrophy of the gastric: mucosa and cystic dilations of the gastri c glands: and fatty Infiltration with hemosiderosis of the liver. The fact that the only survivor was treated early emphasizes the need fbr very early diagnosis and treatment, which is probably the only means o f avoiding death or permanent neurologic damage.