# Leukoencephalopathy with Calcifications and Cysts--The First Polish Patient with Labrune Syndrome
## 4 Discussion  
In 1996, [PERSON] et al. described a new disorder in three unrelated children. It was a triad of LCC as a separate entity. Diagnosis of LCC was based on clinical and neuroradiological findings with the histological examination in some patients [1; 5]. In 2016, it was confirmed that LCC was a novel single-gene disorder due to germ-line biallelic mutation in the box C/D snoRNA [2]. Those authors analyzed the clinical data and the biological samples of 40 patients with LCC over a period of 12 years. In 2016, [PERSON] et al. identified eight mutations of the same gene in patients from unrelated families [4]. The last information on genetic background was described by [PERSON] et al. [6]. Due to the progressive nature of the disease, follow-up MRI and the clinical observations are of primary importance, as a single examination is not sufficient to establish the diagnosis [7]. Discrepancy between the relative well-being of our patient and abnormal imaging findings poses difficulties in diagnosis. Patients with LCC may complain of focal neurological deficits, progressive extrapyramidal, pyramidal and cerebellar symptoms, headaches and/or seizures. In most, cognitive deficits are also reported. We observed a discrepancy between clinical and radiological data in our patient. The subject was a normally developing girl who sought medical attention for recurrent headaches only. Differential diagnosis was difficult, especially with slowly occurring changes in the follow-up imaging studies. First, calcifications in the basal ganglia on CT prompted further diagnostic testing. Basal ganglia calcifications on CT (which were found in our patient in the first neuroimaging) are non-specific, and may occur in many diseases as a primary or secondary sign. They may be idiopathic, toxic (carbon monoxide, lead exposure), infectious (TORCH complex, AIDS), metabolic (hypoparathyroidism, pseudohypoparathyroidismyroidism, Cockayne syndrome I and II, mitochondrial diseases (MELAS, MERRF), neuroferritinopathy, neurodegeneration with brain iron accumulation--NBIA) and inherited in origin (chromosomal abnormalities: _SLC20A2 8p11.21 PDGFRB 5q32 PDGFB 22q13.1 XPR1 1q25.3 MYORG 9p13.3)_.  
Figure 5: Follow-up MRI of the brain, axial plane in the T2 FLAIR sequence; (**a**) First MRI—at the age of 7 years; (**b**) Second MRI 6 months later; (**c**) Third MRI 1 year later—progression of calcifications, cysts in the left thalamus with the mass effect on MRI and white matter abnormalities. In our case, the CT finding of basal ganglia calcifications prompted wide chemical and metabolic testing, which resulted in the exclusion of infectious, toxic or metabolic origin. Fahr disease can reveal bilateral deep nuclei and subcortical calcifications without white matter abnormalities, which were found in our patient. Endocrinopathies (e.g., hypo, hyper-parathyroidism) were relatively easily excluded by laboratory testing. White matter changes found on the first MRI extended the diagnosis to leukodystrophy with calcifications. However, they were not useful in establishing the diagnosis. When infectious, toxic and hormonal factors were excluded, further metabolic investigation was necessary. Leukoencephalopathy with possible calcifications is known to occur in patients after radio- or chemotherapy, which was not observed in our case. The development of cysts with the progression of leukoencephalopathy on the third follow-up MRI examination added to the differential diagnosis, which concentrated on LCC. In Aicardi-Goutieres syndrome, severe symptoms can already be present in infancy. Our patient was seven years old, and brain cysts were not typical of this syndrome. The symptoms of RNASET-2 deficient encephalopathy can also be present in infancy. However, the triad of leukoencephalopathy, calcifications and cysts is often observed. The older age of our patient and the clinical picture with further genetic testing were crucial for the differential diagnosis [8].