A Clinical Guide to Inherited Metabolic Diseases
Authors: David Luyt
Journal: Journal of the Royal Society of Medicine (2003)

Whenever the possibility of an inherited metabolic disease is broached on the ward round, I shudder. These children are usually very sick and young, offering few diagnostic clues. My first instinct is to seek advice from my esteemed colleagues in the biochemistry laboratory, hoping that annual leave or travel to a congress will not rob me of salvation from this source. But Dr Clarke's concise yet inclusive book has made me feel less dependent on such help.

The number of disorders that have been attributed to inherited point defects in metabolism now exceeds 500. These are individually rare but collectively account for a substantial proportion of illness, especially in children. I had often asked myself how the non-expert clinician could ever get a grip on this complex topic. ‘Had’ because Clarke offers a problem-oriented approach that includes the investigations required and exhaustive tabulation of differential diagnoses. After an introductory chapter on disease mechanisms he groups the syndromes by clinical presentation—neurological (chronic and acute encephalopathy, stroke, movement disorder, myopathy and psychiatric); metabolic acidosis; hepatic (jaundice, hepatomegaly, hypoglycaemia, hepatocellular dysfunction); cardiac (cardiomyopathy, arrhythmias, coronary artery disease); storage syndromes; and dysmorphism. Then follow chapters on acute metabolic illness in the newborn, newborn screening, laboratory investigations and treatment.

So that is the scope, but what about the content. Does the text lead the perplexed clinician towards the right conclusion? Take metabolic acidosis—a common presentation that has the ability to mystify and deceive when it may be no more than severe shock with poor perfusion and lactic acidosis. It is also a common presenting or coincident feature of many inherited metabolic diseases. Clarke elegantly guides the reader towards timely diagnostic decisions. Some of his clinical ‘pearls’ are: that metabolic acidosis may be ‘so mild that the generally recognized clinical signs, such as tachypnea, are absent or so subtle that they are missed’; that ‘In other cases, the patient presents with an episode of acute, severe, even life-threatening, acidosis, and the underlying persistence of the condition is only recognised after resolution of the acute episode’; and that ‘the most frustrating presentation is infrequent bouts of recurrent, acute acidosis separated by long intervals of apparent good health during which diagnostic tests show no significant abnormality’. In his approach to metabolic acidosis, Clarke first asks whether it is a result of abnormal losses of bicarbonate or accumulation of acid; in other words, is the anion gap normal or expanded? This division is crucial as it is the latter in which inherited metabolic diseases reside, so the reader learns at an early stage the direction of the investigation. Accumulated acids are lactic acids, ketoacids or organic acids. The differential diagnosis and description of these is exhaustive; a three-page table of the organic acidurias is just one example. There is not space here to offer accounts of the other chapters, all of which are just as impressive.

If your clinical work brings you into contact with patients who may be hiding an inherited metabolic disease, Clarke's Guide is for you. Clearly it will be of greatest help to paediatricians. My friends in the biochemistry laboratory will be allowed to borrow my copy, on the understanding that I get it back before they go away.