Organic Acidemias

Thomas, Janet A.

doi:10.1007/978-3-319-14621-8_17

Cited by 3 publications

(10 citation statements)

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“…At initial presentation of neonates, the normal diet of breast milk or formula, together with postpartum catabolism, causes acute decompensation. In patients with OAs beyond the neonatal period, acute attacks are usually triggered by conditions that increase catabolism, such as fasting, vomiting or febrile infections (Table 1 ) [ 5 , 13 , 16 ].…”

Section: Clinical Presentation Of Oasmentioning

confidence: 99%

“…In the newborn period, poor feeding, vomiting, dehydration, lethargy, tachycardia and hypothermia (Table 1 ) usually develop within 2–7 days after birth [ 3 , 13 ] and, if left untreated, can quickly progress to respiratory distress, coma and death [ 16 , 17 ]. However, as these symptoms are also observed in more common conditions, such as infection, a high index of suspicion should be maintained [ 18 ].…”

Section: Clinical Presentation Of Oasmentioning

confidence: 99%

“…After the neonatal period, OAs may present with delays in development, failure to thrive, altered mental state, abnormal tone, seizures and motor dysfunction [ 16 , 20 , 21 ]. Other signs and symptoms of acute or chronic decompensation can include weight loss (often seen in newborns) and bone-marrow suppression in PA and MMA, and the characteristic ‘sweaty feet’ odour in patients with IVA [ 16 , 22 – 24 ].…”

Section: Clinical Presentation Of Oasmentioning

confidence: 99%

“…All the classical OAs are inherited as autosomal recessive traits [ 17 ] and are caused by a deficiency in the enzymes involved in breaking down amino acids (isoleucine, valine, methionine and threonine in PA and MMA, and leucine in IVA) and additional substrates (odd-chain fatty acids, cholesterol, nucleotides in PA and MMA) [ 14 , 16 , 17 , 25 , 26 ] (Fig. 1 ).…”

Section: Biochemical Pathogenesis Of Oasmentioning

confidence: 99%

“…PA is caused by a deficiency in propionyl-coenzyme A (CoA) carboxylase, composed of alpha and beta subunits encoded by the PCCA and PCCB genes, respectively [ 17 ]. MMA can be caused by a deficiency of multiple enzymes affecting either the transformation of cobalamin to adenosylcobalamin, or the activity of methylmalonyl-CoA mutase, or racemase [ 16 , 17 , 27 , 28 ]. IVA is caused by a deficiency in isovaleryl-CoA dehydrogenase [ 16 , 17 ].…”

Section: Biochemical Pathogenesis Of Oasmentioning

confidence: 99%

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Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories

Häberle

Chakrapani

Mew

et al. 2018

Orphanet J Rare Dis

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BackgroundThe ‘classic’ organic acidaemias (OAs) (propionic, methylmalonic and isovaleric) typically present in neonates or infants as acute metabolic decompensation with encephalopathy. This is frequently accompanied by severe hyperammonaemia and constitutes a metabolic emergency, as increased ammonia levels and accumulating toxic metabolites are associated with life-threatening neurological complications. Repeated and frequent episodes of hyperammonaemia (alongside metabolic decompensations) can result in impaired growth and intellectual disability, the severity of which increase with longer duration of hyperammonaemia. Due to the urgency required, diagnostic evaluation and initial management of patients with suspected OAs should proceed simultaneously. Paediatricians, who do not have specialist knowledge of metabolic disorders, have the challenging task of facilitating a timely diagnosis and treatment. This article outlines how the underlying pathophysiology and biochemistry of the organic acidaemias are closely linked to their clinical presentation and management, and provides practical advice for decision-making during early, acute hyperammonaemia and metabolic decompensation in neonates and infants with organic acidaemias.Clinical managementThe acute management of hyperammonaemia in organic acidaemias requires administration of intravenous calories as glucose and lipids to promote anabolism, carnitine to promote urinary excretion of urinary organic acid esters, and correction of metabolic acidosis with the substitution of bicarbonate for chloride in intravenous fluids. It may also include the administration of ammonia scavengers such as sodium benzoate or sodium phenylbutyrate. Treatment with N-carbamyl-L-glutamate can rapidly normalise ammonia levels by stimulating the first step of the urea cycle.ConclusionsOur understanding of optimal treatment strategies for organic acidaemias is still evolving. Timely diagnosis is essential and best achieved by the early identification of hyperammonaemia and metabolic acidosis. Correcting metabolic imbalance and hyperammonaemia are critical to prevent brain damage in affected patients.

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Section: Clinical Presentation Of Oasmentioning

confidence: 99%