Familial Chylomicronemia Syndrome Presenting as Encephalopathy in an Infant

A report describes the case of a four-month-old male infant who presented with acute encephalopathy and symptoms of elevated intracranial pressure (vomiting, periods of lethargy alternating with periods of irritability, bulging fontanel), reduced appetite, and failure to thrive. Two days before admission, he had a fever. He was the first child of non-consanguineous parents, born at term, and exclusively breastfed. Family history was unremarkable. Previous medical history included a small cyst in the left choroid plexus detected on head ultrasound after birth.

Physical examination revealed pallor, macrocephaly (head circumference 46 cm), mild generalized hypotonia, and an underdeveloped left ear, without any other dysmorphic features. Pupils were responsive to light, and other neurological findings were age-appropriate.On initial venipuncture, strawberry-milky blood was observed.

The infant was admitted to the neurology ward. A computed tomography (CT) scan revealed a lipid accumulation along the right tentorium measuring 23 × 16 × 12 mm, initially thought to be an epidermoid or dermoid cyst causing compression of adjacent structures. Additionally, diffuse extra-axial lipid deposits were observed supra-and infratentorial, as well as within the sinuses and other brain veins.

This was interpreted as rupture of the cyst with dissemination of fatty deposits intravascular and extra-axial. Neurosurgical consultation considered cyst removal due to raised intracranial pressure and encephalopathy. However, a milky blood appearance suggested an underlying disorder.

Laboratory tests revealed that blood gas analysis was normal, while blood glucose was mildly elevated at 7.4 mmol/L. Other electrolytes and urinary amylase were within normal limits. Hematocrit was low at 9.8%, with a normal platelet count and elevated leukocytes. No organomegaly was noted, and the abdominal ultrasound was normal. Echocardiography revealed mild left ventricular enlargement with normal contractile function.

The patient remained stable, so CT was reevaluated and an MRI was performed, revealing intravascular lipid deposits causing venous stasis and formation of collateral venous blood vessels. Agenesis of the outer left ear canal was found, and it was thought that strawberry milky blood and brain lipid deposits suggested a genetic lipid disorder. Environmental factors, glycogen storage disease, and hypothyroidism were excluded, narrowing the diagnosis to dyslipoproteinemias.

Ophthalmologic examination revealed fatty deposits at the retinal periphery without papilledema. Electroencephalography showed bilateral intermittent slow activity in the parietal-temporal-occipital regions, with no epileptiform activity. Cerebrospinal fluid analysis was entirely normal.  Genetic testing from a buccal swab identified two heterozygous pathogenic variants in the LPL gene: c.337 T > C, p.(Trp113Arg) and c.805G > A, p.(Glu269Lys), listed in the ClinVar database. Serum amylase, lipase, and thyroid hormone levels remained normal throughout hospitalization.

A follow-up brain CT in the second week of hospitalization showed no significant changes from the initial scan, aside from slight regression of the lipid deposits. Before discharge, cranial ultrasound at five months revealed no ventricular dilatation, with hyper-echoic linear formations observed in both subarachnoid and intravascular spaces, sparing the ventricles.

Upon arrival at the PICU, the patient received intravenous dexamethasone and antibiotics, along with gastroprotective therapy, and feeding was paused. Plasmapheresis was initially attempted but was stopped due to inefficient filtration. An exchange transfusion was then performed, replacing double the blood volume without complications, allowing measurement of triglycerides (106.8 mmol/L) and cholesterol (normal). Three additional plasmapheresis sessions with 20% albumin were performed three more times. Aside from mild, controlled hypertension, no other complications occurred. Neurological symptoms resolved except for mild hypotonia, and anemia improved.

The patient also received continuous IV insulin and glucose for four days, followed by a low-fat, high medium-chain triglyceride formula (Monogen), which reduced triglycerides to 8 mmol/L. L-carnitine, coenzyme Q, omega-3 fatty acids, and a short course of fibrates were initially given but stopped after genetic confirmation of familial chylomicronemia syndrome. An alternating dairy/dairy-free diet raised triglycerides to 20 mmol/L, so the patient was switched to an exclusively medium-chain triglyceride formula, maintaining triglycerides at 9–10 mmol/L during follow-up. The infant’s neurological status was normal at discharge except for mild hypotonia; he was thriving with a good appetite.

Reference:

Kalanj J, Cobeljic MG, Jesic M, Zdravkovic V, Cvetkovic M, Vukasinovic N, Andjelkovic M, Rsovac S. An unusual case of type I hyperlipidemia-infant with acute encephalopathy, bulging fontanel, vomiting and pink blood: a case report. BMC pediatrics. 2024 Dec 19;24(1):815.

https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-024-05287-9