Chapter 100. Megaloblastic Anemias (Part 10)

Tropical Sprue Nearly all patients with acute and subacute tropical sprue show malabsorption of cobalamin; this may persist as the principal abnormality in the chronic form of the disease, when the patient may present with megaloblastic anemia or neuropathy due to cobalamin deficiency. Absorption of cobalamin usually improves after antibiotic therapy and, in the early stages, folic acid therapy.Fish Tapeworm InfestationThe fish tapeworm (Diphyllobothrium latum) lives in the small intestine of humans and accumulates cobalamin from food, rendering this unavailable for absorption. Individuals acquire the worm by eating raw or partly cooked fish. Infestation is common around the lakes...
Nội dung trích xuất từ tài liệu:
Chapter 100. Megaloblastic Anemias (Part 10) Chapter 100. Megaloblastic Anemias (Part 10) Tropical Sprue Nearly all patients with acute and subacute tropical sprue showmalabsorption of cobalamin; this may persist as the principal abnormality in thechronic form of the disease, when the patient may present with megaloblasticanemia or neuropathy due to cobalamin deficiency. Absorption of cobalaminusually improves after antibiotic therapy and, in the early stages, folic acidtherapy. Fish Tapeworm Infestation The fish tapeworm (Diphyllobothrium latum) lives in the small intestine ofhumans and accumulates cobalamin from food, rendering this unavailable forabsorption. Individuals acquire the worm by eating raw or partly cooked fish.Infestation is common around the lakes of Scandinavia, Germany, Japan, NorthAmerica, and Russia. Megaloblastic anemia or cobalamin neuropathy occurs onlyin those with a heavy infestation. Gluten-Induced Enteropathy Malabsorption of cobalamin occurs in ~30% of untreated patients(presumably those in whom the disease extends to the ileum). Cobalamindeficiency is not severe in these patients and is corrected with a gluten-free diet. Severe Chronic Pancreatitis In this condition, lack of trypsin is thought to cause dietary cobalaminattached to gastric non-IF (R) binder to be unavailable for absorption. It has alsobeen proposed that in pancreatitis, the concentration of calcium ions in the ileumfalls below the level needed to maintain normal cobalamin absorption. HIV Infection Serum cobalamin levels tend to fall in patients with HIV infection and aresubnormal in 10–35% of those with AIDS. Malabsorption of cobalamin notcorrected by IF has been shown in some, but not all, patients with subnormalserum cobalamin levels. Cobalamin deficiency sufficiently severe to causemegaloblastic anemia or neuropathy is rare. Zollinger–Ellison Syndrome Malabsorption of cobalamin has been reported in the Zollinger–Ellisonsyndrome. It is thought that there is a failure to release cobalamin from R-bindingprotein due to inactivation of pancreatic trypsin by high acidity, as well asinterference with IF binding of cobalamin. Radiotherapy Both total-body irradiation and local radiotherapy to the ileum (e.g., as acomplication of radiotherapy for carcinoma of the cervix) may causemalabsorption of cobalamin. Graft-versus-Host Disease This commonly affects the small intestine. Malabsorption of cobalamin dueto abnormal gut flora, as well as damage to ileal mucosa, is frequent. Drugs The drugs that have been reported to cause malabsorption of cobalamin arelisted in Table 100-4. Megaloblastic anemia due to these drugs is, however, rare. Abnormalities of Cobalamin Metabolism Congenital Transcobalamin II Deficiency or Abnormality Infants with TC II deficiency usually present with megaloblastic anemiawithin a few weeks of birth. Serum cobalamin and folate levels are normal, but theanemia responds to massive (e.g., 1 mg three times weekly) injections ofcobalamin. Some cases show neurologic complications. The protein may bepresent but functionally inert. Genetic abnormalities found include mutations of anintra-exonic cryptic splice site, extensive deletion, single nucleotide deletion,nonsense mutation, and an RNA editing defect. Malabsorption of cobalaminoccurs in all cases and serum immunoglobulins are usually reduced. Failure toinstitute adequate cobalamin therapy or treatment with folic acid may lead toneurologic damage. Congenital Methylmalonic Acidemia and Aciduria The infants with this abnormality are ill from birth with vomiting, failure tothrive, severe metabolic acidosis, ketosis, and mental retardation. Anemia, ifpresent, is normocytic and normoblastic. The condition may be due to a functionaldefect in either mitochondrial methylmalonyl CoA mutase or its cofactoradocobalamin. Mutations in the methylmalonyl CoA mutase are not responsive, oronly poorly responsive, to treatment with cobalamin. A proportion of the infantswith failure of adocobalamin synthesis respond to cobalamin in large doses. Somechildren have combined methylmalonic aciduria and homocystinuria due todefective formation of both cobalamin coenzymes. This usually presents in thefirst year of life with feeding difficulties, developmental delay, microcephaly,seizures, hypotonia, and megaloblastic anemia.