Murat DoganOsman OzdemirErtan A. SalS. Zehra DoganPinar OzdemirYasar CesurHüseyin CaksenJournal of Tropical Pediatrics, Volume 55, Issue 3, June 2009, Pages 205–207, https://doi.org/10.1093/tropej/fmn112Published: 18 December 2008

Abstract

Vitamin B12 and folate deficiency causing neuropsychiatric and thrombotic manifestations, such as peripheral neuropathy, subacute combined degeneration of cord, dementia, ataxia, optic atrophy, catatonia, psychosis, mood disturbances, myocardial infarction and portal vein thrombosis are well known. This present report highlights an unusual presentation of vitamin B12 deficiency—psychotic disorder, extrapyramidal symptoms in a 12-year-old boy. His symptoms responded to parenteral vitamin B12 therapy. So with this report we emphasized that serum vitamin B12 and folate levels should be measured, especially in those patients who present with other known neuropsychiatric features of vitamin B12 and folate deficiency.

Introduction

Vitamin B12 deficiency resulting in various neuropsychiatric and thrombotic manifestations, such as neuropathy, myelopathy, myeloneuropathy, dementia, cerebellar ataxia, optic atrophy, psychosis and mood disturbances, portal vein thrombosis, myocardial infarction are well known [1–3]. In addition, recurrent seizures and extrapyramidal system involvement due to vitamin B12 deficiency in adults has been described only recently [4]. But in our knowledge, there has not been any reported psychotic disorder with extrapyramidal involvement in older children. All the reported articles were about adult patients. In this report, a 12-year-old boy presented with psychotic disorder and reversible extrapyramidal symptoms.

Case report

A 12-year-old boy presented with aphasia, tremor and nervousness that lasted for 2-year duration. The patient, who was wholly healthy initially, had given up his schooling 2 years ago without any reason, and had started to become introverted. At that time he had stopped eating, sometimes for up to three days. He had become angry and had begun to hit his mother and brothers. Self-care had been reduced and he had become bedridden and could not even walk and sleep. He had been speaking and smiling to himself. The tremors had begun six months ago.

On physical examination, he had an expressionless face and reduced blink rate. He could not answer to questions; only speak hypnophonic but meaningless sounds. Saccadic eye movements were slow. He had cogwheel rigidity of all limbs and resting tremors of both hands. Tendon reflexes were reduced and clonus was determined on hands and foods. Plantar reflexes were flexor. Sensory, cerebellar and autonomic systems were normal. There was no preceding history of encephalitis or prior use of antipsychotic or antiemetic medications. He had no risk factors for atherosclerosis. There was no history of exposure to carbon monoxide or organophosphate compounds.

Investigations were as follows: hemoglobin was 13.6 g dl−1, reticulocyte count was 0.1% and mean corpuscular volume (MCV) was 98 fl. Serum vitamin B12 level was <150 pg ml−1 and folate was 2.9 ng ml−1. Hypersegmented polymorphs on peripheral smear and megaloblastic changes on bone marrow examination were not determined. Serum parathormone, ceruloplasmin and thyroid function tests were normal. HIV (ELISA) was negative. Tandem mass metabolic screening test, cerebral and vertebral magnetic resonance imaging, right upper and bilateral lower extremity electromyography, bilateral somatosensorial evoked potentials and cerebrospinal fluid analysis were normal. A diagnosis of psychotic disorder and extrapyramidal symptoms secondary to vitamin B12 and folate deficiency was made. Twenty-four hour urine copper level was in normal range. Kayser Fleischer ring was not determined. He was started on vitamin B12 injections at a dose of 1000 mg day−1 and folate 5 mg twice in a week with which he showed improvement within one week. In the seven days of hospitalization, he had no tremors and begun to walk, speak, and was functioning independently.

Discussion

Mostly, the unusual manifestations of vitamin B12 deficiency were reported in literature. Rajkumar et al. [5] reported an unusual presentation of long-standing psychotic symptoms without anaemia in a 31-year-old male, who presented to a tertiary care psychiatric facility. A case of a 44-year-old patient with unusual clinical presentation of encephalomyelopolyneuropathy in vitamin B12 deficiency was presented by Atanassova et al. [6]. On the other hand, a 52-year-old female with psychiatric symptoms, who was treated with vitamin B12 as the only specific therapy, was reported by Berry N et al. [7]. They also reported complete remission of psychiatric symptoms without recurrence for the next 4 years. Dworakowska D et al. [2] presented a case report about Hyperhomocysteinemia complicated by myocardial infarction and portal vein thrombosis. In that paper they showed case report of woman with hyperhomocysteinemia, who developed several complications, probably because of hyperhomocysteinemia. This patient, at the age of 38 and 44 years, developed twice myocardial infarction, and at the age of 48 she suffered from portal vein thrombosis. The patient was treated with the use of folic acid, vitamin B12 and B6 supplementation, and normalization of hyperhomocysteinemia level was received. This case report underlines how important role the vitamin supplementation plays in the case of hyperhomocysteinemia. The early treatment of hyperhomocysteinemia might limit thromboembolic complication [2]. A 44-year-old women victim of a frontal ischemic stroke was presented by Leemann et al. [8]. In their report, extensive evaluation was normal, except for high plasma level of homocysteine in the context of pernicious anemia, otherwise asymptomatic.

Neurological involvement often occurs along with macrocytic anemia, but can occur in the absence of anemia or macrocytosis [9]. It is unclear why vitamin B12 deficiency leads to neurological disease in some and hematological disease in others. Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been postulated to protect the vitamin B12-deficient patients against anemia and homozygosity for MTHFR C677T gene could cause the dissociation between hematological and neurological disease seen in some patients with vitamin B12 deficiency [10]. The mechanism of extrapyramidal involvement in vitamin B12 deficiency is not completely understood. However, indirect evidence may be obtained from our knowledge. Methymalonic acidemia (MMA), an inborn error of metabolism, usually presents with acute extrapyramidal syndrome in infants, and some cases respond to vitamin B12 therapy. Brain imaging and autopsy studies in MMA have shown symmetrical involvement of basal ganglia [11]. On the other hand, folates interact with excitatory kainic acid receptors in the mammalian brain and have agonistic activity at these receptors. Since kainic acid is a potential neurotoxin, folate too may share this property. Methytetrahydrofolate levels are markedly elevated in vitamin B12 deficiency and may be responsible for neuronal destruction. Injection of kainic acid into the basal ganglia in experimental animals leads to a pattern similar to Huntington’s chorea [11]. In our case report, the patient had severe neurological, but no hematologic, findings. Also, beside vitamin B12 deficiency, folate deficiency was determined in our patient too. So this deficiency could be exacerbated by the neurological findings. Marked improvement with vitamin B12 and folate therapy further strengthened the diagnosis. Extrapyramidal involvement due to vitamin B12 deficiency in the child is very rare and previous articles only reported on adults. So to our knowledge, this was the first case report with B12 and folate deficiency presented with psychotic disorder and extrapyramidal symptoms.

In conclusion, psychotic disorder and extrapyramidal symptoms can be a rare manifestation of vitamin B12 and folate deficiency, which are reversible with therapy. Serum B12 and folate levels should be checked in patients who do not have an obvious cause for an extrapyramidal symptoms.

References

1Healton EB,  Savage DG,  Brust JC, et al. Neurologic aspects of cobalamin deficiency, Medicine, 1991, vol. 70 (pg. 229-45)

Google ScholarCrossrefPubMed 2Dworakowska D,  Kazimierska E,  Weyer-Hepka J, et al. Hyperhomocysteinemia complicated by myocardial infarction and portal vein thrombosis–case report, Pol Arch Med Wewn, 2006, vol. 115 (pg. 234-37) (in Polish)

Google ScholarPubMed 3Kanbay M,  Karakus S,  Yılmaz U. Portal vein thrombosis due to hyperhomocysteinemia caused by vitamin B-12 deficiency, Dig DisSci, 2005, vol. 50 (pg. 2362-63)

Google Scholar 4Kumar S. Recurrent seizures: an unusual manifestation of vitamin B12 deficiency, Neurol India, 2004, vol. 52 (pg. 122-3)

Google ScholarPubMed 5Rajkumar AP,  Jebaraj P. Chronic psychosis associated with vitamin B12 deficiency, J Assoc Physicians India, 2008, vol. 56 (pg. 115-16)

Google ScholarPubMed 6Atanassova PA,  Chalakova NT,  Goranov SE, et al. A case of encephalomyelopolyneuropathy in vitamin B12 deficiency, Folia Med, 2004, vol. 46 (pg. 52-4)

Google Scholar 7Berry N,  Sagar R,  Tripathi BM. Catatonia and other psychiatric symptoms with vitamin B12 deficiency, Acta Psychiatr Scand, 2003, vol. 108 (pg. 156-9)

Google ScholarCrossrefPubMed 8Leemann B,  Boughanem N,  Schnider A. Ischemic, an uncommon complication of Biermer disease (pernicious anemia), Rev Neurol, 2006, vol. 162 (pg. 1007-10)

Google ScholarCrossrefPubMed 9Lindenbaum J,  Healton EB,  Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis, N Engl J Med, 1988, vol. 318 (pg. 1720-8)

Google ScholarCrossrefPubMed 10Kvittingen EA,  Spangen S,  Lindemans J, et al. Methionine synthase deficiency without megaloblastic anemia, Eur J Pediatr, 1997, vol. 56 (pg. 925-30)

Google ScholarCrossref 11Kumar S. Vitamin B12 deficiency presenting with an acute reversible extrapyramidal syndrome, Neurol India, 2004, vol. 52 (pg. 507-9)

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