Fabry Disease with Acute Cerebral Infarction Onset in a Young Patient
Fabry disease (FD) is a rare, recessive X-linked hereditary disorder that primarily affects children and adolescents. The disease is characterized by the accumulation of globotriaosylceramide (Gb3) in various cells, including those of the kidneys, blood vessels, and nervous system, leading to multisystem damage. The average time from symptom onset to definitive diagnosis is 13.7 years in male patients and 16.3 years in female patients, highlighting the challenges in timely diagnosis and treatment. This case report discusses a 27-year-old male patient who presented with acute cerebral infarction as the initial clinical manifestation of FD, aiming to enhance the understanding of this condition among healthcare professionals.
The patient, a 27-year-old man, reported experiencing double vision for six days. He occasionally suffered from headaches but had no nausea, vomiting, vertigo, dysarthria, or movement disorders. His medical history included smoking, intermittent diarrhea, and allergic rhinitis. Vital signs were within normal limits: temperature 36.5°C, blood pressure 118/85 mmHg, heart rate 67 beats/min, and respirations 18 breaths/min. Neurological examination revealed diplopia but was otherwise unremarkable. There was no family history of neurological disorders.
Magnetic resonance imaging (MRI) showed a long T2 signal in the left cerebral peduncles. Magnetic resonance angiography (MRA) indicated normal anterior and posterior circulation arteries. Three-dimensional volumetric isotropic turbo spin echo acquisition (3D-VISTA) revealed arterial wall thickening in the bilateral vertebral artery, basilar artery, and bilateral posterior cerebral artery. Urinary ultrasound showed no abnormalities in the kidneys or ureters.
Laboratory findings included elevated serum homocysteine at 44.70 mmol/L (normal: 0–20 mmol/L) and low folic acid at 1.80 ng/mL (normal: 3.1–19.9 ng/mL). High-sensitivity C-reactive protein was elevated at 11 mg/L (normal: 0–3.5 mg/L), and the erythrocyte sedimentation rate was 70 mm/1h (normal: 0–15 mm/1h). The nuclear antibody test was granule 1:100 positive. Lumbar puncture revealed increased cranial pressure at 240 mmH2O (normal: 80–180 mmH2O), elevated cerebrospinal fluid protein at 0.67 g/L (normal: 0.15–0.45 g/L), and decreased glucose at 2.05 mmol/L (normal: 2.3–4.1 mmol/L). Cerebrospinal fluid immunoglobulin IgG was elevated at 68 mg/L (normal: 0–34 mg/L). Cytology showed a white blood cell count of 27 × 10^6/L, with 63% lymphocytes, 31% neutrophils, and 6% monocytes. GQ1b antibody and Aquaporin 4 (AQP4) tests were negative. Myelin basic protein in cerebrospinal fluid was elevated at 2.88 (normal: <0.55). Urine routine examination showed proteinuria (PRO) 3+. Twenty-four-hour urine analysis revealed elevated alpha1 microglobulin at 29.32 mg/24h (normal: <24 mg/24h), IgG at 106.80 mg/24h (normal: 0–17.0 mg/24h), LAM light chain at 22.68 mg/24h (normal: <7.8 mg/24h), KAP light chain at 40.40 mg/24h (normal: <14.2 mg/24h), and total protein at 3.44 g/24h (normal: <0.2 g/24h). Microalbumin was significantly elevated at 2492 mg/24h (normal: 0–60 mg/24h).
A repeat lumbar puncture showed improved cranial pressure at 150 mmHg, with cerebrospinal fluid protein at 0.57 g/L, glucose at 2.30 mmol/L, and leukocytes at 10 × 10^6/L. Cerebrospinal fluid immunoglobulin IgG was 55.8 mg/L. Cytology revealed a small number of lymphocytes and red blood cells, with no abnormal cells.
Renal biopsy under light microscopy showed 23 glomeruli, with 10 being sclerotic. The remaining glomeruli exhibited mild diffuse hyperplasia of mesangial cells and matrix, with nodular hyperplasia. Diffuse podocyte swelling, marked vacuolar degeneration, and a foamy appearance were observed. Tubular epithelial cells showed vacuolar degeneration, with multifocal foamy epithelial cells and tubular atrophy. Renal interstitial focal lymphoid and macrophage infiltration with mild fibrosis were noted. Vascular degeneration was occasionally seen in small arterial walls. Immunofluorescence and electron microscopy findings were consistent with FD nephropathy.
Genetic testing identified the c.426C>A (p.Cys142Ter) variant in the alpha-galactosidase A gene, a known causative mutation of FD.
FD, also known as Anderson FD, is named after Johann Fabry and William Anderson. It is a lysosomal storage disease characterized by the accumulation of Gb3 in various cells, leading to multisystem damage. Over 50% of male patients and about 20% of female patients with FD develop renal disease, with proteinuria being a key indicator of renal damage. Central nervous system involvement often manifests as transient ischemic attacks and ischemic strokes. The incidence of stroke in FD patients aged 25 to 44 is 12 times higher than in the general population, with an average onset age of about 40 years.
This case highlights the importance of considering FD in young patients presenting with stroke and proteinuria, even in the absence of a family history. High-resolution MRI vascular wall imaging can provide critical diagnostic information. Pathologic examination and genetic testing are essential for timely diagnosis and appropriate management. Treatment involves enzyme replacement therapy with recombinant alpha-galactosidase A and symptomatic management. In this case, the patient received symptomatic treatment, resulting in slight improvement in diplopia before discharge.
doi.org/10.1097/CM9.0000000000000089
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