Inherited metabolic disorders… …do not miss treatable diseases…

In the latest issue of Pediatric Endocrinology, Diabetes and Metabolism, readers will have the opportunity to read an interesting publication on the emotional and behavioral functioning of patients with tyrosinemia type 1. This prompted the need to recall information on the numerous inherited metabolic disorders (IMD).
The term IMD, formerly known as inborn errors of metabolism (IEM), was first introduced in 1908 by an English physician Archibald Garrod who analyzing the histories of families with alkaptonuria, linked abnormalities in biochemical reactions to hereditary phenomena. This group includes conditions in which primary alterations of biochemical pathways are related to specific biochemical, clinical and/or pathophysiological features.
The IMD forms a heterogeneous group of genetically determined disorders that are mostly inherited but can also arise from spontaneous mutations. Regarding this group, autosomal recessive inheritance is most common, but all other modes of inheritance, including mitochondrial, are possible. Environmental and epigenetic factors are also involved in their clinical presentation. Inherited metabolic disorders belong to rare conditions, i.e. diseases that occur at a frequency of less than 5×/10 000 births. Although individual ones may be described in only single families worldwide, collectively they occur frequently. According to one of the most recent IMD classifications (An International Classification of Inherited Metabolic Disorders – JIMD 2021 January; 44 (1): 164–177), the group of genetically determined metabolic disorders includes nearly 1,500 diseases assigned to one of 124 categories but new diseases are described almost every month.
In most of IMD, monogenic enzyme defects in the metabolism of carbohydrates, fats, proteins, purines and pyrimidines, steroids, metals, porphyrins, as well as disorders of renal tubular transport, metabolism of cofactors and minerals, or neurotransmission defects underlie their pathogenesis. In daily practice, the 2014 classification by Saudubray and Charpentier which divides IMD into disorders of complex molecules, intoxication disorders and energy deficiency, is especially useful. Approximately 50% of IMDs are already manifested in the neonatal period, while the remaining ones show symptoms in infancy, older children and adults, including very advanced age. Their clinical symptomatology is very broad with one or more tissues and organs involved.
A breakthrough...


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