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Infantile tremor syndrome with megaloblastic anemia – A case report
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Received: ,
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How to cite this article: Ganesh V, Singhal L. Infantile tremor syndrome with megaloblastic anemia – A case report. Med India. 2026;5:49-52. doi: 10.25259/MEDINDIA_45_2025
Abstract
Infantile tremor syndrome (ITS) is a self-limiting clinical condition primarily affecting infants. It is characterized by a constellation of symptoms, including coarse tremors, often exacerbated by wakefulness and mitigated during sleep, anemia, distinctive skin pigmentation changes, developmental regression, and hypotonia in seemingly well-nourished infants. While a definitive etiology remains elusive, various hypotheses have been proposed, including infectious, metabolic, and nutritional factors. A growing body of evidence implicates Vitamin B12 deficiency as a significant contributor to ITS pathogenesis, though this association remains a subject of ongoing debate. In the absence of a conclusive diagnosis, empirical management often involves a multifaceted approach. Nutritional supplementation with iron, calcium, magnesium, Vitamin B12, and other essential micronutrients is a cornerstone of treatment. Pharmacotherapy, primarily with propranolol, may be employed to alleviate tremors, though other drugs may be considered in refractory cases.
Keywords
B12 deficiency
Cerebral atrophy
Neurology
Neuroregression syndrome
Pediatric
INTRODUCTION
This case report presents a 9-month-old female infant who exhibited a progressive decline characterized by tremors, feeding difficulties, and developmental delay. The infant had been exclusively breastfed by a vegetarian mother, and the absence of adequate complementary feeding exacerbated the nutritional deficiencies. Clinical evaluation revealed pallor, hypopigmentation of hair, hyperpigmentation of knuckles [Figure 1a and b], and generalized hypotonia. Laboratory investigations confirmed a diagnosis of vitamin B12 deficiency anemia, along with other nutritional deficits [Table 1]. Neuroimaging studies demonstrated cerebral atrophy, indicating the potential neurological sequelae of prolonged nutritional deprivation [Figure 2]. The therapeutic approach focused on addressing the underlying nutritional deficiencies primarily through supplementation with Vitamin B12, iron, magnesium, and calcium, coupled with a protein-rich diet.
| Parameters | Reports | Normal range |
|---|---|---|
| Hemoglobin and hematocrit | 5.8/34.1 | 11–13 g/dL |
| Total leukocyte count | 7040 | 3000–10,000 |
| Platelet | 1.39 lakhs | >1.5 lakhs |
| Reticulocyte count | 1.74 | <1 |
| Total iron binding capacity | 285 | <250 |
| Vitamin B12 level | 104 pg/mL | 211–710 pg/mL |
| Serum homocysteine | 97.99 | - |
| Serum thyroid profile | Normal limits | - |
| HPLC | HbA-97.99 | - |
| TMS/GCMS | Elevated methylmalonyl -CoA levels | - |
HPLC: High-performance liquid chromatography, HbA: Hemoglobin A, TMS: Tandem mass spectrometry, GCMS: Gas chromatography-mass spectrometry, CoA: Methylmalonyl coenzyme A.
CASE REPORT
A 9-month-old female infant, a product of non-consanguineous marriage with spontaneous conception was born at term to a hypothyroid mother who is graduate, belongs to a strict vegetarian diet along with social economic background of lower middle class nuclear family, presented with a complex clinical picture over the preceding month, she had experienced a concerning regression in her developmental milestones, indicating a decline in her neurocognitive function. This was further compounded by the onset of involuntary limb movements, or jitteriness, within the past week. In addition, a notable darkening of her skin pigmentation emerged [Figure 1a and b], appearing suddenly over her body despite a fair complexion trait in her family. Her birth history was unremarkable, with a normal vaginal delivery and a healthy neonatal period. Antenatal ultrasounds, while largely unremarkable, did identify a choroid plexus cyst in the second trimester; a follow-up postnatal scan was found to be normal. The presentational anthropometry was length – 64 cm (−3 SD), weight – 5.5 kg (−3 SD), and occipitofrontal circumference (OFC) – 40 cm (−3 SD), indicating severe wasting with microcephaly. On physical examination, the infant appeared pale, and the most striking finding was the hyperpigmentation of her extremities and neck, along with tremor movements elicited at both wrists and ankles. The central nervous system examination revealed generalized hypotonia with loss of axial tone and head holding, with the slip sign positive on examination. Despite the hypotonia, her reflexes were intact. Rest all other systemic examination was unremarkable.
Investigations and management
The infant was admitted as a case of generalized hypotonia with severe nutritional anemia and microcephaly (under evaluation). The investigations in Table 1 revealed severe macrocytic hyperchromic anemia on peripheral smear with lower vitamin B12 levels, along with serum methylmalonyl coA and homocysteine levels. The baby started on injection hydroxocobalamin 1000 mcg daily (14 days), followed by weekly injection and further oral supplementation. The child responded well to treatment in the form of active limb movements with resolution of milestones and adequate weight gain during the hospital stay. On discharge follow-up, the neurological examination was normal with absent tremors and adequate weight gain.
DISCUSSION
Infantile tremor syndrome (ITS) is a clinical condition characterized by a constellation of symptoms including tremors, anemia, skin pigmentation abnormalities, developmental regression, and muscle weakness.[1] Primarily prevalent in the Indian subcontinent, ITS is a self-limiting disorder affecting infants and young children.[2] Despite decades of research, the precise etiology of this enigmatic condition remains elusive. ITS is a self-limiting condition primarily affecting infants aged 5–36 months in the Indian subcontinent. Its characteristic features include coarse tremors, anemia, skin pigmentation abnormalities, and developmental regression, often observed in seemingly well-nourished infants. Despite decades of research, the underlying cause of ITS remains elusive, posing an enduring medical mystery.[3] There are few literatures stating the incidence of ITS mostly during winter/rainy seasons, and a higher incidence is mostly noted in Karnataka.[4,5] The sex predominance of the male gender, as well as socioeconomic status with mothers often vegetarians, are some other important leading factors for ITS.
Clinical presentation
Variable clinical presentation from bizarre presentation of neuro regression to a typical scenario often appears malnutrition characteristic (severe acute malnutrition with anemia), hidden hunger (micronutrient deficiency). Tremors, mostly coarse character (facial muscles and hands), are one of the most significant characteristic features of ITS. These tremors are typically absent during the early course of illness. The bleating of a goat’s voice is another finding in these patients, which has been noticed.[5,6] Other movement disorders include myoclonus and chorea.[5] Systemic involvement may be noticed as hyperpigmentation of knuckles and flexors, along with some characteristic features of severe acute malnutrition and moderate acute malnutrition. Congestive cardiac failure secondary to super-added thiamine deficiency has also been reported.[5] Bone marrow features are variable, from normoblastic to megaloblastic appearance. Successful treatment with Vitamin B12 alone has been observed with a uniform pattern of response resulting in dramatic improvement in symptoms with rapid hematological and neurological recovery.[5] Supportive care in the form of intravenous fluids to treat and prevent dehydration, antibiotics for associated infections, and other medications to treat associated complications are commonly used during the acute phase. Tremors have been treated with propranolol and sedatives, but their role in treatment requires evaluation through controlled studies.
Treatment
Most often, ITS infants were symptomatically managed with multivitamins and a methylcobalamin regimen of 14 days (1000 mcg) followed by 1000 mcg/week for 6 weeks every month till symptoms disappear or anemia is corrected. Recovery is gradually noticed in terms of clinical response (resolution of mental abilities, tremors, and disappearance of hyperpigmentation). Refractory diseases require further genetic testing in terms of malabsorption syndromes (ImerslundGräsbeck syndrome; CUBAM [cubilin-amnionless complex receptor defect], hereditary intrinsic factor deficiency).
CONCLUSION
ITS is a condition caused by nutritional deficiencies, primarily characterized by its impact on the nervous system. Children with ITS also consistently show signs of megaloblastic anemia. This syndrome is most often seen in families facing socioeconomic challenges, particularly where mothers follow a vegetarian diet lacking essential nutrients. Effective treatment for ITS involves multivitamin therapy, with a particular focus on Vitamin B12 supplementation, along with addressing any other nutritional deficits. Supportive care is also crucial for comprehensive management. Early diagnosis and treatment are vital to prevent long-term cognitive problems.
Author contributions:
VG: Contributed to the preparation and drafting of the manuscript; had primary responsibility for writing the original draft; LS: Contributed to the conceptualization of the research ideas; formulation of overarching research goals and aims; and maintenance and management of research data.
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understands that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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