Abstract / Summary
F-box and leucine-rich repeat protein 4 (FBXL4) deficiency is a rare mitochondrial disorder typically characterized by lactic acidosis, hypotonia, and developmental delay.Feeding difficulties and poor growth may dominate the presentation and initially suggest a gastrointestinal disorder.A Moroccan girl born to consanguineous parents had reduced oral intake, recurrent vomiting, and poor growth from birth, accompanied by hypotonia and developmental delay.At eight months, she was admitted with metabolic decompensation and severe undernutrition: weight was 4.8 kg, length 60 cm, weight-forlength z score -2.30, and mid-upper arm circumference 10.5 cm, meeting the criterion for severe acute malnutrition.Blood lactate ranged from 6.35 to 15.88 mmol/L.Brain magnetic resonance imaging showed cerebral atrophy and bilateral symmetric white-matter abnormalities.Proband-only exome sequencing identified the homozygous FBXL4 frameshift variant NM_001278716.2:c.851del,p.(Pro284LeufsTer7), classified as pathogenic by the laboratory.Parental segregation analysis had not been performed.Continuous nasogastric feeding with progressively increased energy intake was associated with a weight increase to 5.8 kg over a two-month hospitalization.Despite temporary stabilization, the patient died at 12 months during a respiratory infection complicated by metabolic decompensation.This observation documents the substantial nutritional burden of FBXL4-related disease.Severe feeding difficulties accompanied by hypotonia, developmental delay, and metabolic abnormalities warrant investigation for a multisystem disorder, while nutritional support remains an immediate management priority.