PMC8143529_01
(A) Massive micro-macrovacuolar steatohepatitis picture with minimal fibrosis at liver biopsy with hematoxylin-eosin 10x and (B) Periodic Acid-Schiff, 20x. (C) Magnetic Resonance examination in the pre-treatment showed the overall signal from thigh muscles slightly reduced and clearly inhomogeneous, due to the hypointensity of posterior muscles, compatible with a diffuse fat infiltration in a Fat-Suppressed acquisition technique. (D) After 10-month treatment the overall Magnetic Resonance signal from thigh muscles is higher and less inhomogeneous, with a signal increase of the posterior muscles indicating a reduced fat infiltration. (E) Pedigree of the family of the patient with Multiple Acyl-CoA Dehydrogenase Deficiency (MADD).
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F1
Due to a persistent elevation of serum enzymes, a liver biopsy was performed and it showed a massive micro-macrovacuolar steatohepatitis picture with minimal fibrosis without signs of inflammation (Figures 1A,B). Magnetic Resonance Imaging [1.5 Tesla Philips MR equipment, Turbo Spin Echo Fat Suppressed T2w technique (TR 7014 ms, TE 100 ms, FA 90 ), using 5 mm thick slices and 2 excitations] was indicative of lipid storage of thighs muscles (mild, Figure 1C), and confirmed liver steatosis (severe) as well. The proband's sister did not show the variant (Figure 1E). Control Magnetic Resonance Imaging, after 10 months of therapy, showed absent/sharp decrease of lipid storage of thighs muscles (Figure 1D).
(A) Fluctuating trend of Aspartate (AST) and Alanine (ALT) aminotransferases from the onset of the symptoms to the present moment. The arrow indicates the start of riboflavin treatment. ALT and AST upper normal values are 40 U/L. (B) Plasma C3 to C16 acylcarnitine concentrations in our patient in July 2019 at the onset of symptoms (blue), in February 2020 after three months from the start of therapy (red), and in August 2020 after 9 months of therapy (green).
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F2
During follow-up, amounts of serum acylcarnitines and urinary organic acids fluctuated paralleling serum transaminases, with highest values manifest during periods of illness (e.g., flu) or catabolic stress (e.g., protracted fasting), confirming the recurrent nature of episodes in MADD (Supplementary Table 1 and Figures 2A,B).