Researchers presented the case of a patient with glutaric aciduria type IIC likely experiencing hemophagocytic lymphocytosis (HLH) in a case report published in Frontiers in Immunology.

HLH is usually caused by inborn errors of immunity and can also be secondary to inborn errors of metabolism. In recent decades, the inborn errors of metabolism reportedly associated with HLH include lysosomal storage diseases, such as lysosomal acid lipase deficiency, including Wolman disease. 

Read more about lysosomal acid lipase deficiency etiology 

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Glutaric aciduria is caused by errors in fatty acid oxidation and the abnormal function of a number of mitochondrial dehydrogenase enzymes. Its onset most commonly begins in childhood, and the disease is characterized by neurological symptoms accompanied by repeated hypoglycemia, hyperlipidemia, and hyperlactic acidemia. 

The case report presented by Huang and colleagues details a 27-year-old woman who presented with persistent upper and lower limb weakness over the past decade. She had a previous misdiagnosis of seronegative polymyositis.

Upon admission, the patient developed repeated episodes of hypoglycemia, hyperlactic acidemia, and hyperlipidemia. On day 5, she experienced respiratory failure, liver failure, and anuria and was transferred to the critical care unit. Whole genome sequencing revealed a homozygous mutation of the ETFDH gene (c.250G>A), and the patient was diagnosed with glutaric aciduria type IIC.

Additional tests and imaging were performed, the most significant of which was bone marrow biopsy and aspiration. The research team wrote, “There are eight diagnostic criteria for hemophagocytic lymphocytosis, and the patient met six of them, including persistent fever, splenomegaly, cytopenias, increased ferritin, hypertriglyceridemia and hypofibrinogenemia, and hemophagocytosis in the bone marrow.” Her physicians hence suspected a diagnosis of HLH, but the patient eventually died of gastrointestinal bleeding a month and a half after admission and her family declined an autopsy. 

Huang et al concluded, “This case provides evidence for the relationship between [inborn errors of metabolism] and impaired immune function. When cytopenias occur in [inborn errors of metabolism] patients, HLH is a possible complication that cannot be ignored.” 


Huang L, Wu W, Zhu Y, Yu H, Tang L, Fang X. Case report: hemophagocytic lymphocytosis in a patient with glutaric aciduria type IICFront Immunol. 2022;12:810677. doi:10.3389/fimmu.2021.810677