Vitamin deficiencies cause specific disease states that reflect the biochemical functions of each vitamin. Deficiencies can result from inadequate intake, impaired absorption, increased requirements, or drug interactions.
Causes of Vitamin Deficiency
Primary deficiency results from inadequate dietary intake, often in the setting of food scarcity, restrictive diets, or alcoholism. Secondary deficiency results from malabsorption syndromes such as celiac disease, Crohn disease, and pancreatic insufficiency. Increased requirements occur during pregnancy, lactation, infancy, and certain diseases. Drug interactions can cause deficiency: isoniazid antagonizes B6, methotrexate antagonizes folate, and anticonvulsants interfere with vitamin D metabolism.
Beriberi
Beriberi results from thiamine deficiency, historically from a diet of polished rice. Thiamine pyrophosphate is a cofactor for key enzymes in the citric acid cycle, including pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. Wet beriberi presents with high-output heart failure, edema, and vasodilation. Dry beriberi presents with peripheral neuropathy, paresthesias, and muscle wasting. Shoshin beriberi is a fulminant cardiovascular form with acute hemodynamic collapse. Thiamine deficiency in alcoholism causes Wernicke encephalopathy with confusion, ataxia, and nystagmus, which can progress to Korsakoff psychosis with amnesia and confabulation.
Pellagra
Pellagra results from niacin deficiency, historically common in populations relying on corn as a staple food, where niacin is bound and unavailable. The classic presentation includes the three Ds: dermatitis in sun-exposed areas, diarrhea from gastrointestinal involvement, and dementia with confusion, hallucinations, and memory loss. Death occurs without treatment. Secondary pellagra occurs with carcinoid syndrome, where tryptophan is diverted to serotonin synthesis.
Scurvy
Scurvy results from vitamin C deficiency. Early symptoms include fatigue, malaise, and gingival swelling. Later manifestations include perifollicular hemorrhages, ecchymoses, impaired wound healing, hyperkeratosis, and corkscrew hairs. Musculoskeletal pain from subperiosteal hemorrhage occurs in advanced cases. Scurvy is fatal without treatment but resolves rapidly with vitamin C supplementation.
Rickets and Osteomalacia
Rickets in children and osteomalacia in adults result from vitamin D deficiency. Rickets causes softening and deformity of growing bones with bowed legs, rachitic rosary at the costochondral junctions, and frontal bossing of the skull. Hypocalcemia causes tetany and seizures. Osteomalacia causes bone pain, proximal muscle weakness, and insufficiency fractures. Both respond to vitamin D and calcium supplementation.
Megaloblastic Anemia
Megaloblastic anemia results from deficiency of either folate or vitamin B12, both required for DNA synthesis. Impaired nucleotide synthesis causes ineffective erythropoiesis with large, oval macrocytes and hypersegmented neutrophils. Bone marrow shows megaloblastic changes with nuclear-cytoplasmic asynchrony.
Folate deficiency causes megaloblastic anemia without neurological symptoms, seen in pregnancy, alcoholism, and malabsorption. B12 deficiency additionally causes neurological symptoms including peripheral neuropathy, loss of vibratory sense, and subacute combined degeneration of the spinal cord. Pernicious anemia is the autoimmune form with intrinsic factor deficiency. Supplementation with folate alone corrects the anemia but allows neurological deterioration in B12 deficiency.
Vitamin K Deficiency
Vitamin K deficiency impairs synthesis of functional clotting factors II, VII, IX, and X, prolonging prothrombin time. Manifestations include easy bruising, epistaxis, and bleeding from wounds. Newborns are at particular risk because of sterile intestines and low hepatic stores, receiving prophylactic vitamin K at birth. Malabsorption syndromes and warfarin therapy are common causes in adults.
Vitamin A Deficiency
Vitamin A deficiency is a leading cause of preventable blindness worldwide. Early effects include night blindness due to impaired rhodopsin regeneration. Progression leads to xerophthalmia with conjunctival dryness, Bitot spots, corneal ulceration, and keratomalacia. Immune function is impaired, increasing infection risk. The WHO recommends high-dose vitamin A supplementation in areas of endemic deficiency.
B-Complex Deficiency Syndromes
Riboflavin deficiency causes angular stomatitis, cheilitis, and glossitis. B6 deficiency causes dermatitis, microcytic anemia, and neurological symptoms. Biotin deficiency causes periorificial dermatitis, alopecia, and neurological abnormalities. Pantothenic acid deficiency is rare and causes fatigue, insomnia, and gastrointestinal symptoms.
