Introduction

Imerslund-Gräsbeck syndrome is an autosomal recessive inherited disease^1-3 characterized by poor absorption of vitamin B₁₂⁴. It manifests with megaloblastic anemia⁵ and proteinuria without affecting kidney function since the receptor is identical to cubilin, which also binds to albumin and other proteins; therefore, it participates in the tubular reabsorption of urine proteins^3-6. This diagnosis should be considered when the three typical characteristics are present: macrocytic anemia, low serum vitamin B₁₂ levels, and proteinuria without kidney disease^7-9.

This pathology is caused by a mutation of the cubilin gene (CUBN) on chromosome 10 or the amnionless gene (AMN) on chromosome 14, provoking a defect in the receptor for the vitamin B12-intrinsic factor complex of the ileal enterocyte^5,10,11. This manuscript presents the case of a patient with Imerslund-Gräsbeck syndrome.

Clinical case

A 58-year-old woman was taken by ambulance to the emergency room due to four episodes of generalized tonic movements of unknown duration accompanied by sphincter relaxation and supraversion without recovery of consciousness in the interictal periods. The crisis was controlled with midazolam 2 mg. Her companion said it was the first time she had exhibited such symptoms; however, he deemed it relevant to report that the patient had lost 10 kg in the last month. Within the history, he commented that she had a diagnosis of depression and atypical Parkinson’s disease (MSA type) under management with quetiapine, escitalopram, levodopa, carbidopa, and clonazepam (completed one week before the picture).

On physical examination, she had normal vital signs. She was alert, oriented, and cooperative, with euthymia, bradypsychia, and bradylalia without death or delusional ideas, no alteration of cranial nerves, independent gait with a severe alteration of balance, and ataxic gait with limitation in the range of movements of large joints in the limbs associated with counting coins at rest. Paraclinical tests were performed, which turned out normal. So, given these findings, it was suspected that the patient was having a first seizure episode secondary to benzodiazepine withdrawal. However, cyanocobalamin deficiency, gait alterations, and constitutional syndrome drew our attention, requiring further studies.

Extension tests included a gastroduodenoscopy that reported chronic atrophic pangastritis without Helicobacter pylori, a colonoscopy within normal limits, and a negative fecal occult blood test. The genetic study of individual exome sequencing reported an alteration of the CUBN gene, compatible with Imerslund-Gräsbeck syndrome type 1; thus, it was decided to continue management with cyanocobalamin and assessment by nutrition, achieving an adequate evolution. The patient was eventually discharged.

Discussion

Imerslund-Gräsbeck syndrome, also known as juvenile megaloblastic anemia or hereditary megaloblastic anemia, is a syndrome whose representative characteristic is a vitamin B₁₂ deficiency, along with megaloblastic anemia and proteinuria¹². This disease occurs more frequently in Europe, with an incidence of five per million people in Scandinavian countries¹³.

The clinical picture is characterized by vitamin B12 deficiency, megaloblastic anemia, and proteinuria without renal involvement secondary to this deficiency. Signs such as palpitations, sweating, dizziness, and slow-onset heart failure may also be found¹³, and some may present with anatomical anomalies of the urinary tract, neurological manifestations, and growth retardation¹⁴. Digestive disorders include anorexia, diarrhea, angular stomatitis, and a smooth, intense red depapillated tongue painful to the touch called Hunter’s glossitis⁹.

For diagnosis, tests such as serum vitamin B₁₂¹ levels, which will be decreased and are associated with macrocytic anemia, are performed initially and as a guide. Meanwhile, the level of anti-intrinsic factor antibodies, anti-parietal cell antibodies, and gastrin levels could be evaluated¹. However, the genetic study confirms the diagnosis of this pathological entity^13,14.

Treatment involves supplementation therapy with vitamin B₁₂. Its doses are adjusted, according to the patient: In children, it starts with 1 mg/day for 3 days and then once a month, while in adults, a daily dose of 1 mg is administered intramuscularly for a week, followed by injections administered weekly for 4 weeks, and then for a month. If administered orally, the recommended dose is 1 to 2 mg daily^15-17.

Conclusion

This pathology is of low prevalence and is most frequently identified early (under 10); however, some patients can reach advanced ages. The characteristic triad of these patients is vitamin B₁₂ deficiency with macrocytic anemia, neurological symptoms in older patients, and proteinuria without renal involvement, which requires prior suspicion and confirmation through a genetic study. Management is based on supplementation with cyanocobalamin.