Table 1 Diagnostic features and management of the most common IMDs triggered by proteins
From: Food triggers and inherited metabolic disorders: a challenge to the pediatrician
Disorders triggered by proteins | |||||
|---|---|---|---|---|---|
UCDs | LPI | OAs | MSUD | HI/HA | |
Newborn screening | Distal defects | No | Yes | Yes | No |
Food triggers | Protein load | Protein load | Protein load | Protein load | Protein load (leucine sensitivity) |
Age of onset | Variable. From a few days after birth (complete enzymatic deficiencies) to adult age (partial enzymatic deficiencies) | Variable. Common during weaning | Variable. From a few days after birth (complete enzymatic deficiencies) to adult age (partial enzymatic deficiencies) | Variable. From a few days after birth (complete enzymatic deficiencies) to adult age (partial enzymatic deficiencies) | After the first few months of life |
Main presenting features | Acute or episodic encephalopathy with lethargy and vomiting, liver failure, spontaneous protein aversion | Recurrent emesis and/or diarrhea, episodes of postprandially altered mental status. Strong aversion to high-protein foods by the age of 1 year | Acute or episodic encephalopathy with lethargy and vomiting | Acute or episodic encephalopathy with lethargy and vomiting. Maple syrup odor | Recurrent episodes of profound hypoglycemia induced by fasting and protein-rich meals |
Main routine laboratory findings | Hyperammonemia | Postprandial hyperammonemia, high levels of LDH and ferritin, hypertriglyceridemia | Ketoacidosis, hyperammonemia, hyperlactatemia | Ketoacidosis | Persistent mild or moderate hyperammonemia, recurrent hypoketotic hypoglycemia |
Diagnostic confirmation | Plasma amino acid analysis, urinary orotic acid dosage. Genetic testing | Plasma and urinary amino acid analysis. Genetic testing | Urinary organic acid analysis, plasma acylcarnitine profile. Genetic testing | Plasma amino acid analysis, urinary organic acid profile. Genetic testing | Genetic testing |
Acute management | Specialist centre. Stop protein intake, ammonia detoxification, measures to reverse catabolism | Specialist centre. Stop protein intake, ammonia detoxification, measures to reverse catabolism | Specialist centre. Stop protein intake, ammonia detoxification, measures to reverse catabolism | Specialist centre. Stop protein intake, leucine and BCKAs detoxification, measures to reverse catabolism | Specialist centre. Prompt correction of hypoglycemia |
Chronic management | - Protein-restricted diet - adequate energy intake - ammonia scavengers - oral arginine or citrulline supplementation - liver transplantation for selected patients | - Protein-restricted diet - adequate energy intake - ammonia scavengers - oral lysine and citrulline supplementation | - Protein-restricted diet - adequate energy intake - ammonia scavengers - defect-specific amino acids supplementation - liver/kidney transplantation for selected patients | - Protein-restricted diet - adequate energy intake - oral isoleucine and valine supplementation - liver transplantation for selected patients | - Protein-restricted diet - oral diazoxide |
Natural history | Variable. The duration and severity of hyperammonemia strongly correlate with brain damage | Variable. The duration and severity of hyperammonemia strongly correlate with brain damage. Late complications may be fatal | Variable. The duration and severity of acidosis and hyperammonemia strongly correlate with brain damage. Late complications may be fatal | Variable. The duration and severity of coma strongly correlate with brain damage | Variable. The duration and severity of hypoglycemias strongly correlate with brain damage. Increased frequency of generalized seizures |