Clinical Manifestations

Thiamine deficiency can develop within 2-3 mo of a deficient intake. Early symptoms of thiamine deficiency are nonspecific such as fatigue, apathy, irritability, depression, drowsiness, poor mental concentration, anorexia, nausea, and abdominal discomfort. As the condition progresses, more-specific manifestations of beriberi such as peripheral neuritis (manifesting as tingling, burning, paresthesias of the toes and feet), decreased deep tendon reflexes, loss of vibration sense, tenderness and cramping of the leg muscles, congestive heart failure, and psychic disturbances develop. Patients can have ptosis of the eyelids and atrophy of the optic nerve. Hoarseness or aphonia caused by paralysis of the laryngeal nerve is a characteristic sign. Muscle atrophy and tenderness of the nerve trunks are followed by ataxia, loss of coordination, and loss of deep sensation. Later signs include increased intracranial pressure, meningismus, and coma. The clinical picture of thiamine deficiency is usually divided into a dry (neuritic) type and a wet (cardiac) type. The disease is wet or dry depending on the amount of fluid that accumulates in the body due to factors such as cardiac and renal dysfunction, even though the exact cause for this edema has not been explained. Many cases of thiamine deficiency show a mixture of the 2 main features and are more properly termed thiamine deficiency with cardiopathy and peripheral neuropathy.

The classic clinical triad of Wernicke encephalopathy (mental status changes, ocular signs, ataxia) is rarely reported in infants and young children with severe deficiency secondary to malignancies or feeding of defective formula. An epidemic of life-threatening thiamine deficiency was seen in infants fed a defective soy-based formula that had undetectable thiamine levels. Manifestations included emesis, lethargy, restlessness, ophthalmoplegia, abdominal distention, developmental delay, failure to thrive, lactic acidosis, nystagmus, diarrhea, apnea, and seizures. Intercurrent illnesses that resembled Wernicke encephalopathy often precipitated the symptoms.

Death from thiamine deficiency usually is secondary to cardiac involvement. The initial signs are slight cyanosis and dyspnea, but tachycardia, enlargement of the liver, loss of consciousness, and convulsions can develop rapidly. The heart, especially the right side, is enlarged. The electrocardiogram shows an increased Q-T interval, inverted T waves, and low voltage. These changes as well as the cardiomegaly rapidly revert to normal with treatment, but without prompt treatment, cardiac failure can develop rapidly and result in death. In fatal cases of beriberi, lesions are located principally in the heart, peripheral nerves, subcutaneous tissue, and serous cavities. The heart is dilated, and fatty degeneration of the myocardium is common. Generalized edema or edema of the legs, serous effusions, and venous engorgement are often present. Degeneration of myelin and axon cylinders of the peripheral nerves, with wallerian degeneration beginning in the distal locations, also is common, particularly in the lower extremities. Lesions in the brain include vascular dilation and hemorrhage.

Diagnosis

The diagnosis is often suspected on the basis of clinical setting and compatible symptoms. Objective biochemical tests of thiamine status include measurement of erythrocyte transketolase activity (ETKA) and the thiamine pyrophosphate effect (TPPE). The biochemical diagnostic criteria of thiamine deficiency consist of low ETKA and high TPPE (normal range, 0-14%). Urinary excretion of thiamine or its metabolites (thiazole or pyrimidine) after an oral loading dose of thiamine may also be measured to help identify the deficiency state. MRI changes of thiamine deficiency in infants are characterized by bilateral symmetric hyperintensities of the frontal lobes and basal ganglia, in addition to the lesions in the periaqueductal region, thalami, and the mammillary bodies described in adults.

Prevention

A maternal diet containing sufficient amounts of thiamine prevents thiamine deficiency in breast-fed infants, and infant formulas marketed in all developed countries provide recommended levels of intake. During complementary feeding, adequate thiamine intake can be achieved with a varied diet that includes meat and enriched or whole-grain cereals. When the staple cereal is polished rice, special efforts need to be made to include legumes and/or nuts in the ration. Thiamine and other vitamins can be retained in rice by parboiling, a process of steaming the rice in the husk before milling. Improvement in cooking techniques, such as not discarding the water used for cooking, minimal washing of grains, and reduction of cooking time help to minimize the thiamine losses during the preparation of food.

Treatment

In the absence of GI disturbances, oral administration of thiamine is effective. Children with cardiac failure, convulsions, or coma should be given 10 mg of thiamine intramuscularly or intravenously daily for the 1st week. This treatment should then be followed by 3-5 mg of thiamine per day orally for at least 6 wk. The response is dramatic in infants and in those having predominantly cardiovascular manifestations, whereas the neurologic response is slow and often incomplete. Patients with beriberi often have other B-complex vitamin deficiencies; therefore, all other B-complex vitamins should also be administered. Treatment of TRMA and other dependency states require higher dosages (100-200 mg/day). The anemia responds well to thiamine administration, and insulin for associated diabetes mellitus can also be discontinued in many cases of TRMA.

Clinical Manifestations

Clinical features of riboflavin deficiency include cheilosis, glossitis, keratitis, conjunctivitis, photophobia, lacrimation, corneal vascularization, and seborrheic dermatitis. Cheilosis begins with pallor at the angles of the mouth and progresses to thinning and maceration of the epithelium, leading to fissures extending radially into the skin (Fig. 46-1). In glossitis, the tongue becomes smooth, with loss of papillary structure (Fig. 46-2). Normochromic, normocytic anemia may also be seen because of the impaired erythropoiesis. A low riboflavin content of the maternal diet has been linked to congenital heart defects, but the evidence is weak.

Figure 46-1 Angular cheilosis with ulceration and crusting.

(Courtesy of National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India.)

Figure 46-2 Glossitis as seen in riboflavin deficiency.

(From Zappe HA, Nuss S, Becker K, et al: Riboflavin deficiency in baltistan (website). www.rzuser.uni-heidelberg.de/%7Ecn6/baltista/ribofl_e.htm. Accessed May 23, 2010.)

Diagnosis

Most often, the diagnosis is based on the clinical features of angular cheilosis in a malnourished child, which responds promptly to riboflavin supplementation. A functional test of riboflavin status is done by measuring the activity of erythrocyte glutathione reductase (EGR), with and without the addition of FAD. An EGR activity coefficient (ratio of EGR activity with added FAD to EGR activity without FAD) of >1.4 is used as an indicator of deficiency. Urinary excretion of riboflavin <30 µg/24 hr also suggests low intakes.

Prevention

The recommended daily allowance (RDA) of riboflavin for infants, children and adolescents is presented in Table 46-1. Adequate consumption of milk, milk products, and eggs prevents riboflavin deficiency. Fortification of cereal products is helpful for those who follow vegan diets or are consuming inadequate amounts of milk products because of other reasons.

Treatment