Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review

Table 1 Clinical and laboratory findings in vitamin B12 deficiency

General symptoms	Weight loss observed in most patients
	Low-grade fever occurs in one third of newly diagnosed patients and promptly disappears with treatment
Gastrointestinal symptoms	Smooth tongue (50% of patients) with loss of papillae. Changes in taste and loss of appetite
	Patients may report either constipation or having several semi-solid bowel movements daily
	Anorexia, nausea, vomiting, heartburn, pyrosis, flatulence and a sense of fullness
Brain	Altered mental status. Cognitive defects (“megaloblastic madness”): depression, mania, irritability, paranoia, delusions, lability
Sensory organs	Optic atrophy, anosmia, loss of taste, glossitis
Bone marrow	Hypercellular bone marrow
	Increased erythroid precursors
	Open, immature nuclear chromatin
	Dyssynchrony between maturation of cytoplasm and nuclei
	Giant bands, metamyelocytes
	Karyorrhexis, dysplasia
	Abnormal results on flow cytometry and cytogenetic analysis
Spinal cord	Myelopathy
	Spongy degeneration
	Paresthesias
	Loss of proprioception: vibration, position, ataxic gait, limb weakness/spasticity (hyperreflexia)
	Positive Romberg sign
	Lhermitte’s sign
	Segmental cutaneous sensory level
Autonomic nervous system	Postural hypotension
	Incontinence
	Impotence
Peripheral nervous system	Cutaneous sensory loss
	Hyporeflexia symmetric weakness
	Paresthesias
Genitourinary symptoms	Urinary retention and impaired micturition may occur because of spinal cord damage. This can predispose patients to urinary tract infections
Reproductive system	Infertility
Abnormalities in infants and children	Developmental delay or regression, permanent disability
	The patient does not smile
	Feeding difficulties
	Hypotonia, lethargy, coma
	Hyperirritability, convulsions, tremors, myoclonus
	Microcephaly
	Choreoathetoid movements, peripheral blood
	Macrocytic red cells, macro-ovalocytes
	Anisocytosis, fragmented forms
	Hypersegmented neutrophils
	Leukopenia, possible immature white cells
	Thrombocytopenia
	Pancytopenia
	Elevated lactate dehydrogenase level (extremes possible)
	Elevated indirect bilirubin and aspartate aminotransferase levels
	Decreased haptoglobin level
	Elevated levels of methylmalonic acid, homocysteine, or both

Table 2 Demographic and biochemical characteristics of chronic atrophic autoimmune gastritis patients with vitamin B12 deficiency

Ref.	Total No. of patients	Gender (M/F)	Age (yr), median	Gastrin (pg/mL), median	Prevalence Vit. B12 deficiency, n (%)	Vitamin B12 (pg/mL) median1	Prevalence of neurological complications
Marignani et al[23], 1999	80	24/56	56	491	44 (55.0)	87.5	NA
Hershko et al[24], 2006	160	53/107	50	846	111 (69.4)	82.0	17%
Annibale et al[25], 2005	140	49/91	55	500	65 (46.5)	80.0	NA
Miceli et al[27], 2012	99	72/27	59	726	37 (37.4)	NA	6%
Lahner et al[26], 2015	83	42/41	59	NA	43 (51.8)	138.0	NA

¹Median vitamin B12 levels in patients with macrocytic anemia at presentation. NA: Not assessed.

Table 3 Summary of the main types of deficit described in chronic atrophic autoimmune gastritis patients

Deficit	Mechanism of action	Effects	Reported prevalence
Vitamin B12	Lack of intrinsic factor reduced vitamin B12 absorption in terminal ileum	Pernicious anemia	37%-69%[24,27]
		Neurological alteration
		Osteopenia/osteoporosis
Iron deficiency	Gastric acid increases the dissolution and ionization of poorly soluble calcium salt	Microcytic anemia	41%[24]
Vitamin C	Destruction of ascorbic acid in the gastric mucosa for elevated pH and bacterial overgrowth	Reduced and oxidative effects	Not known
Calcium	Gastric acid increases the dissolution and ionization of poorly soluble calcium salt	Osteopenia/osteoporosis	Not known
Vitamin D	Not clarified	Secondary hyperparathyroidism	12.1%[84]
		Osteopenia/osteoporosis
		Increased incidence of autoimmune diseases