IllnessMultiple Acyl-CoA Dehydrogenase Deficiency, non-neonatal; differential diagnosis

NGS +

Multiple acyl-CoA dehydrogenase (MADD) deficiency is caused by loss of functional electron transfer flavoprotein in the inner mitochondrial membrane. MADD can be divided into type I (neonatal onset plus congenital anomalies), type II (neonatal) and type III (late onset). Yet age and symptom onset vary widely. The median time between symptom onset and diagnosis is usually several years. Because rare metabolic myopathy is often underestimated, diagnosis of the adult form in particular is often difficult. Late-onset forms of MADD typically present with slowly progressive proximal weakness, myalgia, lethargy, vomiting, hypoglycemia and metabolic acidosis. Most patients respond well to riboflavin substitution and modified diet yielding convincing clinical results. Biochemical confirmation of the diagnosis requires relatively complicated testing, including muscle biopsy, acylcarnitine profiling and urinary organic acid analysis. MADD is inherited in an autosomal recessive manner. Molecular genetic testing includes at least the three core genes ETFA, ETFB and ETFDH, while the differential diagnosis should include many other genes. More than 90% of MADD mutations are identified in the ETFDH gene, but although the diagnostic yield is high, the exact percentage is not known more precisely.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK558236/

• Alias: Glutaric aciduria type 2, mild type
• Alias: Multiple Acyl-CoA Dehydrogenase Deficiency, mild type
• Allelic: Encephalopathy, acute, infection-induced, 4, susceptibility to (CPT2)
• Acyl-CoA dehydrogenase, medium chain, deficiency of (ACADM)
• Brown-Vialetto-Van Laere syndrome 1 (SLC52A3)
• Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
• CPT II deficiency, infantile (CPT2)
• CPT II deficiency, lethal neonatal (CPT2)
• CPT II deficiency, myopathic, stress-induced (CPT2)
• CPT deficiency, hepatic, type IA (CPT1A)
• Carnitine deficiency, systemic primary (SLC22A5)
• Carnitine-acylcarnitine translocase deficiency (SLC25A20)
• Congenital disorder of glycosylation, type It (PGM1)
• Fazio-Londe disease (SLC52A3)
• Glutaric acidemia IIA (ETFA)
• Glutaric acidemia IIB (ETFB)
• Glutaric acidemia IIC (ETFDH)
• Glycogen storage disease VII (PFKM)
• Glycogen storage disease X (PGAM2)
• Glycogen storage disease XI (LDHA)
• Glycogen storage disease XII (ALDOA)
• Glycogen storage disease XIII (ENO3)
• Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency (FLAD1)
• McArdle disease (PGYM)
• Riboflavin deficiency (SLC52A1)
• VLCAD deficiency (ACADVL)