Inborn Errors of Metabolism

Inborn errors of metabolism are defined as abnormalities of the synthesis, transport, or turnover of nutritional and cellular compounds. Individually, they are rare, but as a group, their incidence is about 1 in 1,000. They are typically genetic defects in metabolic enzymes, and as such are inherited. Their pathology arises from depletion of a needed metabolic product or from toxic accumulation of a substrate.

Their clinical presentations vary greatly. Age of onset may be perinatal, or later in life. Course can be acute, subacute, or chronic. By their nature they tend to be multisystem diseases, frequently affecting the nervous system.

Index of suspicion for an inborn error of metabolism should be high if a child presents with neurologic deterioration (change in mental status, seizures, hypotonia, nausea/vomiting, etc.) and any of the following:

• Neuroophthalmologic abnormalities
  
• Abnormal Urine odor
• Congenital acidosis
• Repeated hypoglycemia
• Coarse facies
• Hepatic impairment and/or hepatosplenomegaly
• Renal impairment
• Cardiomyopathy
  

Many inborn errors of metabolism are associated with unusual smells in the urine. These often go unnoticed by the physician, but are detected by a nurse or a parent. These odors may have significant diagnostic value.

Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism. It is associated with odors which are described in the literature as resembling "curry," "maple syrup", "burnt sugar", or "fenugreek."

The description of the odor will vary depending on the cultural background of the person describing the odor. For example, many people from Mediterranean areas are unfamiliar with the scent of maple syrup, and are more likely to describe the scent of the urine as "fenugreek." Folks from California may have no idea what fenugreek is, but are likely to recognize burnt sugar.

There are other urine odors which are described as being associated with specific inborn errors:

• Phenylketonuria (PKU) is associated with a "musty" or "mousy" smell
  
• Cystinuria is associated with a "sulfur" smell
• Isovaleric acidemia, Multiple acyl-Coa dehydrogenase deficiency, and 3-hydroxy-3-methylglutaric aciduria are all associaetd with a "sweaty feet" smell
• Methionine malabsorption is associated with a "cabbage" smell
• The odors associated with Tyrosinemia have been described as resembling "cabbage" or "rancid butter."
• Trimethylaminuria is associated with a "fish market" smell
• Methylmalonic acidemia has been associated wtih an acidic odor

References:


1. Pastores, G.M. and Kolodny, E.H. (2004). Inborn errors of metabolism of the nervous system. In Bradley, W.G., Daroff, R.B., Fenichel, G.M., and Jankovic, J. (Eds.). Neurology in Clinical Practice, Fourth Edition. Butterworth Heinemann, Philadelphia, pp. 1811-1832.


2. Burton, B.K. (1998). "Inborn errors of metabolism in infancy: a guide to diagnosis." Pediatrics, 102(6) E69. (PMID:9832597)


3. Monastiri, K., Limame, K., Kaabachi, N., Kharrat, H., Bousnina, S., Pousse, H., Radhouane, M., Gueddiche, M.N., and Snoussi, N. (1997). "Fenugreek odour in maple syrup urine disease." J Inherit Metab Dis, 20(4) 614-5. (PMID:9266407)


4. N. Blau, M. Duran, M. E. Blaskovics, K. M. Gibson. (2003).  Physicians Guide to the Laboratory Diagnosis of Metabolic Diseases. Springer-Verlag (ISBN:354042542X)

A superhuge quiz about neurogenetic syndromes, many of which are inborn errors of metabolism.

Hundreds of billions of permutations.