An Unusual Presentation of Fahr Disease: A Case Report

INTRODUCTION

Fahr disease is a rare neurodegenerative disease, also known as idiopathic basal ganglia calcification, bilateral striato-pallido-dentate calcinosis, and primary familial brain calcification.¹ This disease typically manifests between the ages of 40 and 60 years and is often found incidentally on computed tomography (CT) imaging. It is important to rule out secondary causes of brain calcifications to come to a conclusion of Fahr disease. The common symptoms of the disease include both neurological and behavioural, such as vertigo, epilepsy, syncope, cerebellar ataxia, dementia, and movement disorders resembling Parkinson’s disease.² Currently, there is no curative treatment for Fahr disease. The treatment options for the patients are limited and are mostly supportive. This case highlights the importance of considering Fahr disease at an early age and the predominance of neurological and motor symptoms at the early age of presentation.

CASE REPORT

A 28-year-old male presented to the emergency department with complaints of numbness and pain involving both upper and lower limbs for the past year. The symptoms were chronic and progressive in nature. The patient had previously consulted multiple outpatient departments for similar complaints and had been treated symptomatically with analgesics and multiple sessions of interferential therapy, with minimal relief.

Past medical history revealed an episode of seizures at the age of ten years, which was not formally evaluated or treated. Childhood history of infections was considered, but did not have any significant findings. Family history was notable for the death of his brother at 18 years of age, who had been receiving treatment for type 1 diabetes mellitus. The patient also has two sisters who are reportedly healthy with no neurological complaints. Family screening and genetic testing were not performed because of limited availability and financial constraints.

On physical examination, no significant systemic abnormalities were detected. Neurological examination revealed impaired attention and an ataxic gait. There were no focal motor deficits or cranial nerve abnormalities. Cerebellar function testing, including finger-nose testing, heel-shin testing, and rapid alternating movements, was normal. The only cerebellar sign observed was gait ataxia. Formal cognitive assessment using the mini-mental state examination (MMSE) or montreal cognitive assessment (MoCA) was not performed at the time of presentation. Although impaired attention was noted on neurological examination, objective cognitive scoring was unavailable, representing a limitation of this report.

Routine laboratory investigations, including complete blood counts, renal function tests, liver function tests, and thyroid function tests, were within normal limits. Serum electrolyte analysis showed a calcium level of 9.3 mg/dL (reference range: 8.4–11.0 mg/dL). Parathyroid hormone level showed it to be 35 pg/mL (reference range: 15-65 pg/mL). Serum phosphate, magnesium, 1,25-dihydroxy vitamin D levels, and alkaline phosphatase were within normal limits. Serological testing for human immunodeficiency virus was negative. Screening for T: toxoplasmosis, O: other infections like HIV, syphilis, parvovirus B19, varicella and Zika, R: rubella, C: cytomegalovirus, H: herpes simplex virus (TORCH) infections was negative. Autoimmune screening, including antinuclear antibody testing, was negative. Tuberculosis screening was also negative.

Genetic testing for mutations associated with primary familial brain calcification, such as SLC20A2, genes associated with Fahr’s disease (PDGFRB-platelet-derived growth factor receptor beta , PDGFB-platelet-derived growth factor subunit B), and XPR1–xenotropic and polytropic retrovirus receptor 1, was not performed due to limited availability and financial constraints.

Non-contrast computed tomography (NCCT) of the brain revealed extensive symmetrical calcifications involving the cerebral hemispheres, dentate nuclei, and basal ganglia, along with bilateral frontal subcortical and corticomedullary calcifications [Figures 1 and 2]. No significant cortical atrophy or hydrocephalus was reported on the scan. The radiological distribution was classical for primary familial brain calcification (PFBC)/Fahr disease and, together with the metabolic workup, supported the diagnosis.

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Figure 1: Shows extensive symmetrical calcifications involving the cerebral hemispheres, dentate nuclei, and basal ganglia, along with bilateral frontal subcortical and corticomedullary calcifications. No significant cortical atrophy or hydrocephalus

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Figure 2: Shows bilateral symmetrical calcification.

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Treatment options remain limited and are primarily supportive; the patient was managed symptomatically. He was followed up at the neuromedicine where he was initiated on antiepileptic therapy and analgesics.

DISCUSSION

Fahr disease, which is also known as striato- pallido-dentate calcifications or idiopathic basal ganglia calcification (IBGC), is a neurodegenerative disease with an autosomal dominant pattern of inheritance.¹ First characterised by Karl Theodor Fahr in 1930, this rare condition is defined by its progressive, degenerative nature. It presents a challenging clinical picture where intracranial calcifications give a complex group of symptoms. Patients often face a steady decline marked not only by motor and cognitive disabilities but also by the sudden onset of epileptic syncope, cataracts, and systemic neuromuscular irritability manifesting as tetany and paresthesia.² The hereditary nature of this condition often places a heavy burden on families, as it typically maps to an autosomal dominant trait, as discussed. However, the clinical presentation is rarely uniform. This genetic heterogeneity is notable as studies show involvement of the SLC20A2 and PDGFRB genes. These discoveries suggest that the intracranial calcifications observed in this patient are not merely incidental, but are likely driven by specific, underlying cellular transport or signalling defects.³ The genetic heterogeneity of the disease is further underscored by the involvement of the PDGFB and XPR1 loci. Ramos et al. demonstrated these mutations contribute significantly to the disease's causation, moving us towards a model where retrovirus receptor pathways and growth factors play central roles.⁴ While we often categorise intracranial calcifications as incidental, the underlying cause in Fahr's disease is likely rooted in complex metabolic or structural failures. Current literature suggests a link between altered calcium signalling and a wide spectrum of psychiatric illnesses that usually occur in the early stages of Fahr disease. Whether these deposits are the result of a disrupted blood-brain barrier or an intrinsic disorder of neuronal calcium metabolism remains a subject of debate. The finding of increased neuronal calcium sensor 1 in other major psychiatric conditions provides a fascinating insight into how these localised mineral deposits might drive the behavioural and cognitive.⁵

The disease is more common in males than in females and usually manifests after the age of 30 years, as described by Kotan and Ayagu.⁶ In our case, early age presentation marks a deviation from the usual course of the disease. Two distinct variants have been proposed by some studies, such as early onset (age <40) and late onset (age >50). In the early variant, psychiatric symptoms are predominant. The diagnosis of Fahr’s disease is based on the presence of brain calcification on CT scan, together with the clinical manifestations, in the absence of demonstrated alterations in calcium and phosphate serum levels and metabolism. In our case, it is clear that the investigations of calcium and phosphate are within normal limits. When brain imaging is positive for bilateral striopallido-dentate calcification, obtaining serum calcium and parathormone levels should help differentiate Fahr’s disease from hypoparathyroidism, which is the major differential diagnosis. The parathyroid hormone level stays within a limit in our case. Brain CT is more sensitive than traditional MRI in the detection of calcium deposits.⁷ The patient here had a predominant motor symptom, which marks a deviation from the normal course of the disease, as mentioned in the literature. The presence of seizures from the age of ten marks as a notable incident, yet is under-evaluated. Cranial NCCT was taken, as shown in Figure 1, non-contrast CT brain showing extensive bilateral symmetrical calcification involving the basal ganglia and dentate nuclei and in Figure 2, axial CT sections demonstrating additional calcification involving frontal subcortical and corticomedullary regions.⁸

The differential diagnosis of bilateral intracranial calcification includes hypoparathyroidism, pseudohypoparathyroidism, hyperparathyroidism, mitochondrial disorders, TORCH infections, neurocysticercosis, tuberculosis, toxic exposures, and other metabolic or genetic disorders.⁹

No satisfactory treatment has been found for Fahr disease. Treatment is mainly symptomatic and individualised. In our case, antiepileptics and analgesics were provided to the patient.

Recent advances in the understanding of primary familial brain calcification (PFBC) have expanded knowledge regarding its epidemiology and genetic basis. PFBC is estimated to have a prevalence of approximately 0.21–0.66%, although the true prevalence may be higher because many affected individuals remain asymptomatic. Six causative genes have been identified to date, including the autosomal dominant genes SLC20A2, PDGFRB, PDGFB, and XPR1, and the autosomal recessive genes MYORG and JAM2. Current evidence suggests that the pathogenesis of PFBC is related to disturbances in phosphate homeostasis and dysfunction of the neurovascular unit, leading to abnormal calcium deposition within the brain. These findings highlight the genetic and biological heterogeneity of the disease.¹⁰

According to accepted diagnostic criteria for primary familial brain calcification (PFBC), diagnosis is based on the presence of bilateral calcifications involving the basal ganglia and other characteristic brain regions, progressive neurological or neuropsychiatric dysfunction, exclusion of secondary causes of intracranial calcification, and family history or genetic confirmation when available. In the present case, the patient fulfilled these criteria through the demonstration of bilateral symmetrical calcifications involving the basal ganglia and dentate nuclei on CT imaging, progressive neurological symptoms, and comprehensive exclusion of metabolic, infectious, autoimmune, and endocrine causes. Although genetic testing and family screening could not be performed because of financial and logistical constraints, the overall clinical and radiological findings strongly support the diagnosis of PFBC/Fahr disease.¹¹

The present case is noteworthy because of the unusually early age of presentation and predominance of sensory complaints and gait ataxia rather than psychiatric manifestations. Although Fahr disease commonly presents during the fourth to sixth decades of life, younger presentations have been reported. The absence of metabolic abnormalities, together with characteristic bilateral symmetrical intracranial calcifications involving the basal ganglia and dentate nuclei, strongly supports the diagnosis of primary familial brain calcification. This case emphasises the importance of considering Fahr disease in young patients presenting with unexplained chronic neurological symptoms and characteristic neuroimaging findings.

CONCLUSION

The case presented shows us that rarely seen Fahr disease may be considered in patients with motor and neurological deficits. It should also be noted that both neurological and psychiatric symptoms can be the presenting symptoms of the condition, and such patients should be evaluated properly before confirming the diagnosis. Fahr disease should be considered in patients with bilateral symmetrical intracranial calcification that cannot be explained by other causes of intracranial calcification. In our case, the NCCT and the laboratory findings support our diagnosis.