To describe a child with neutropenia and carrying inborn error of metabolism (IEM).

A 10 months-old boy, fist child of non-consanguineous parents, presented severe neutropenia (0.02 × 109/L) with fever, feeding problems, hypertonia and seizures. The frequency of fever and oscillating neutropenia is raised beyond use of antibiotics and granulocyte colony-stimulating factors. Some facial features present during physical examinations (hypertelorism, coarse face and skin dyspigmentation). He has failure to thrive and neuropsychomotor developmental delay. Viral diseases, organic acid in urine and mass spectrometry in tandem was normal. Abdominal ultrasound showed right hydronephrosis. Other image exams not detected alterations. The bone marrow aspirate analysis with karyotype resulted normal, with mild maturation arrest of granulocytic series. He did not have monocytosis or other hematologic disorders. Serum immunoglobulins were normal for the age group. Viral chronic diseases were negative, and she had no other autoimmune disorders. His mother had a first trimester spontaneous abortion, his father has no illnesses, and he has no siblings. A whole exome NGS sequencing showed compound heterozygous: one missense pathogenic CLPB variant (p. Arg408Gly) and other VUS c.1770+2T>A, splicing site. Hospitalizations is still frequent, and neutropenia did not remit to date.

This patient presents neutropenia and neurologic involvement, characteristics of caseinolytic peptidase B (CLPB) deficiency, which can range from severe to mild. In this reported case, a severe CLPB deficiency, death usually occurs at a few months of age due to neonatal neurologic involvement (hypotonia or hypertonia, respiratory insufficiency, swallowing problems, absence of voluntary movements, and epilepsy) and severe neutropenia associated with life-threatening infections. A multidisciplinary team is necessary, and no specific dietary or metabolic treatment is available. Hematopoietic stem cell transplant is not indicated in this case. Granulocyte-colony stimulating factor to increase neutrophil counts to reduce the frequency of infections should be used. Neutropenia associated with CLPB disease is present from birth and may be chronic or intermittent with absolute neutrophil counts ranging from severe (< 0.5 per mm3) to mild (< 1.5 per mm3). Elevated urinary excretion of 3-methylglutaconic acid (3-MGA) (typically 2x-10x higher than the reference range) has been observed in most of affected individuals to date.

This case may be useful to understand the neutropenia in inborn error of metabolism and clinical signs and symptoms of the disease. The molecular evaluation is fundamental to elucidate diagnostic of neutropenia in newborns.