When vitamin B12 deficiency strikes early: A case of pernicious anemia with neurological features

Vigneshvarprashanth Umapathy¹, RM Subbaiah²

¹Resident Internal Medicine, Kauvery Hospital, Tennur, Trichy, Tamil Nadu, India

²Consultant Haemato-oncologist, Kauvery Hospital, Tennur, Trichy, Tamil Nadu, India

Abstract

A young girl presented with long-standing anemia, unsteady gait, generalized fatigue, and hyperpigmentation. She was diagnosed with pernicious anemia, confirmed by the presence of autoantibodies against both parietal cells and intrinsic factor. Notably, she also exhibited neurological manifestations, which is rare at her age. Prior to this presentation, she had visited multiple healthcare facilities over a two-year period without receiving a definitive diagnosis or effective treatment.

Keywords: Pernicious anemia, Vitamin B12, Neuropathy, Myelopathy, Parietal cells, Intrinsic factor, Autoimmune, Hyperpigmentation

Background

Vitamin B12 deficiency is a common global health concern that, if left untreated, can result in a range of hematological and neurological complications. Early recognition and appropriate management of the underlying cause are therefore essential. While pernicious anemia remains the most common cause of Vitamin B12 deficiency worldwide,^1,2 in India, the deficiency is more often attributed to inadequate dietary intake due to a lack of Vitamin B12 rich foods.³

Case Presentation

A 24-year-old woman presented with complaints of unsteady gait, generalized fatigue, and bilateral lower limb swelling lasting for over a week. She reported a two-year history of anemia, for which she had been receiving oral iron therapy. Additionally, she had experienced significant weight loss over the past few months, along with a history of patchy hair loss. She follows a non-vegetarian diet. There was no known history of diabetes, thyroid disorders, renal or liver disease, or recent infections. She also denied any exposure to toxins or heavy metals.

On examination, she was afebrile, conscious, alert and oriented, noted to have pallor, bipedal oedema, hyperpigmentation over the tongue, bilateral hands and feet (Fig. 1). Her vitals were: temperature: 97.5 F, pulse rate: 115/min, BP: 100/60 mmHg, SpO₂: 98% in room air, and respiratory rate: 18/min. Neurological examination revealed mild weakness in the bilateral upper and proximal lower limbs, brisk deep tendon reflexes and bilateral extensor plantar response, suggesting myelopathy. Other systems examination was unremarkable.

Table. 1: Investigations of our patient

Hemoglobin	5.3 g/dl
MCV	108 fl
MCH	34 pg
Total WBC count	3500 cells/mm3
Platelet count	66000/mm3
Corrected reticulocyte count	13 %
Peripheral smear	Macrocytic hypochromic anemia, mild leukopenia and thrombocytopenia
TSH	6.04 uIU/ml
fT3, fT4	Normal
LDH	1505 U/L
Serum vitamin B12	<83 pg/mL (Low)
Serum folate	15.2 ng/mL
Lupus anticoagulant	Not detected
C3, C4	Normal
DCT	Negative
ANA	Negative
Anti-parietal cell antibody	Positive (++)
Anti-IF antibody	Positive (+)
NCS	Bilateral sural sensory axonal neuropathy
MRI whole spine and brain	Not suggestive of SACD

MCV: Mean corpuscular volume, MCH: Mean corpuscular hemoglobin, WBC: White blood cell, TSH: Thyroid stimulating hormone, LDH: Lactate dehydrogenase, DCT: Direct Coombs test, ANA: Anti-nuclear antibody, IF: Intrinsic factor, NCS: Nerve conduction study, SACD: Subacute combined degeneration of the spinal cord

Fig. (1): Hyperpigmentation over tongue, bilateral hands and feet

Diagnosis

Clinical neurological examination was suggestive of non-compressive myelopathy. Investigations revealed severe macrocytic hyperchromic anemia, pancytopenia, and subclinical hypothyroidism. Her serum Vitamin B12 level was low, while folic acid levels remained within the normal range. The combination of hyperpigmentation, macrocytic hyperchromic anemia, pancytopenia, and low Vitamin B12 levels was indicative of megaloblastic anemia secondary to Vitamin B12 deficiency. Given her non-vegetarian diet, an autoimmune etiology was suspected. Further evaluation demonstrated the presence of both parietal cell and intrinsic factor antibodies. Tests for direct Coombs, lupus anticoagulant, and anti-nuclear antibody (ANA) were negative. Surprisingly, MRI whole spine showed no features of SACD.

As intrinsic factor (IF) antibodies are highly specific for pernicious anemia and can confirm the diagnosis,⁴ she was diagnosed with pernicious anemia. Although parietal cell antibodies are present in approximately 90% of patients with pernicious anemia, they are not specific to the condition.⁴ She was managed in hospital with injection Vitamin B12 (cyanocobalamin 1000 mcg) daily for a week intramuscularly, then was advised with weekly and monthly injections. She improved dramatically.

Discussion

Pernicious anemia (PA) is a type of megaloblastic anemia caused by cobalamin (Vitamin B12) deficiency resulting from a lack of intrinsic factor (IF). IF is a glycoprotein essential for Vitamin B12 absorption in the terminal ileum, as it binds to cobalamin and facilitates its uptake. PA is an autoimmune condition, characterized by the presence of autoantibodies targeting intrinsic factor and gastric parietal cells. The condition is also frequently associated with other autoimmune and genetic disorders.^5,6 In this case, the patient was additionally diagnosed with subclinical hypothyroidism and reported patchy hair loss—both of which may represent autoimmune manifestations linked to PA. It is notably rare for PA to present at such a young age, as it typically occurs in individuals between 40 and 70 years.⁷ One study found that 1.9% of patients older than 60 had undiagnosed PA.⁸ Congenital forms of the disease generally present before the age of two.⁴

Further neurological assessment in our patient revealed signs of peripheral neuropathy. However, MRI of whole spine and brain showed no evidence of subacute combined degeneration (SACD) of the spinal cord. This could be explained by the low sensitivity of conventional MRI for SACD of cord, which most often requires clinical diagnosis.⁹ Reports of Vitamin B12 deficiency–related neuropathy in young individuals are scarce in the medical literature. Cyril Jabea Ekabe et al.¹⁰ described a case involving a 28-year-old woman with Vitamin B12 deficiency and peripheral neuropathy. Similarly, Sydney Shaw et al.¹¹ in London documented a case of a 24-year-old woman with pernicious anemia who primarily presented with neurological symptoms.

To conclude, although pernicious anemia is uncommon in younger individuals, early recognition, accurate diagnosis, and prompt treatment are crucial to prevent the progression of hematological and neurological complications.

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When vitamin B12 deficiency strikes early: A case of pernicious anemia with neurological features