Organic aciduria in neonatal multiple carboxylase deficiency

Abstract

A Samoan patient and a Saudi-Arabian patient were found to have abnormalities in the pattern of organic acid metabolites characteristic of 3-methylcrotonylglycinuria, propionic acidaemia and lactic acidosis. Both patients died early in life. The metabolic pattern is diagnostic of multiple carboxylase deficiency and an enzymatic diagnosis was made in a subsequent affected sibling of the first patient. Deficiency of the three carboxylases suggests a primary defect in the metabolism of biotin which is required for their activity. The importance of the recognition of the clinical picture is highlighted by the fact that this lethal disease is readily treated with biotin. These patients have prominent skin lesions which can serve as alerting signs for the diagnosis.

Biotin‐Responsive Infantile Encephalopathy: EEG‐Polygraphic Study of a Case

“…Seizures have been reported as a prominent clinical feature in two of five HCSD cases (Wolf et al, 1981;Narisawa et al, 1982) and in 15 of 28 BD cases (Lehnert et al, 1979;Munnich et al, 1980;1981~;19816; Leonard et al, 1981; Thoene et al, 1981 ;Sherwood et al, 1982;Sweetman et al, 1982;Pocecco et al, 1983;Wolf et al, 19836;Diamantopoulos et al, 1984;Di Rocco et al, 1984;Fois et al, 1986;Low et al, 1986). Seizures have also been reported in an exceptional case of adult-onset form (Bressman et al, 1986) and in acquired biotin deficiency (Kien et al, 1981).…”

“…Seizures have been described as generalized (Lehnert et al, 1979; Leonard et al, 1981; Thoene et al, 1981): grand mal, myoclonic and clonic (also reported in two siblings of a propositus) (Cowan et al, 1979), tonic (Sweetman et al, 1982), and usually myoclonic . But details of EEGs and samples have not been published.…”

Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells

“…These patients, also described as having the neonatal form of multiple carboxylase deficiency (MCD), have life threatening ketoacidosis and organic acidemia (11). They have reduced activity of all biotin-dependent caboxylases: propionyl-CoA carboxylase (PCC), pyruvate carboxylase (PC), methylcrotonyl-CoA carboxylase (MCC), and acetyl-CoA carboxylase (ACC) (12)(13)(14). In these patients, the potentially lethal disruption of gluconeogenesis, fatty acid metabolism, and amino acid catabolism can be reversed with pharmacological doses of biotin.…”

Inheritable Biotin-Treatable Disorders and Associated Phenomena

“…The patient wi th the hi ghe st Km fo r biot in (70 ti mes no rmal) pre se nte d in the fi rst fe w ho urs of life (171) and a previous sibling had died at three days of age (144). The patient wi th the hi ghe st Km fo r biot in (70 ti mes no rmal) pre se nte d in the fi rst fe w ho urs of life (171) and a previous sibling had died at three days of age (144).…”

“…The patient wi th the hi ghe st Km fo r biot in (70 ti mes no rmal) pre se nte d in the fi rst fe w ho urs of life (171) and a previous sibling had died at three days of age (144). In two of tho se the di agnosis was base d on the pre se nce of the ch aracte ri sti c organic aci duri a in sample s studie d po stmo rte m (144). The patient wi th a Km fo r bi otin only th re e ti me s no rmal pre se nte d at ei ght mo nths of age (1 13).…”