Lethal multiple acyl‐CoA dehydrogenation deficiency with dysmorphic features

Abstract

The dysmorphic form of multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II, GAII, McKusick 23168) has only been described in four families to date (Sweetman et al., 1980;Lehnert et al., 1982;Goodman et al., 1983;Boue et al., 1984). Here we report the presentation and diagnosis of a new case of this severe disorder.Infant I. was a female born at 38 weeks gestation after an uneventful pregnancy to Pakistani immigrant parents whose grandparents were first cousins. Labour was precipitated by spontaneous rupture of membranes and was accompanied ~ by a small antepartum haemorrhage. Of five previous pregnancies, one had resulted in intrauterine death at 34 weeks, postmortem examination showing an absent left kidney, and one had resulted at term in a fresh stillbirth showing no congenital anomaly. Of the three live-born infants, two are well and one died aged 18 months in Pakistan.The infant was not asphyxiated at birth, weighed 2.54 kg and developed hypothermia (34.6°C) by the age of one hour. Examination revealed an unresponsive, hypotonic infant with decreased muscle bulk. Apart from talipes equinovarus, there were no joint contractures but there was loss of skin elasticity. There were abnormal facies with small eyes, a larg~ anterior fontanelle and low set ears. There were bilateral renal swellings in the absence of a palpable bladder. Investigations included a blood urea level of 12.7 mmol L-1, a plasma bicarbonate level of 13.1mmolL -1 and a glucose level of 1.7mmolL -1. Routine medical care was given and the infant died aged 21 hours.At the postmortem examination both kidneys were massively enlarged weighing 99 and 95 g respectively. Their cut surfaces showed numerous minute cysts up to 0.2 cm in diameter in the cortex. There was some blurring of the normal cortico--medullary junction and the medulla appeared oedematous and slightly mucoid. The only other abnormality was patchy pallor in the liver.Histology of the kidneys showed numerous cysts in the cortex, lined by cuboidal epithelium. Between the cysts there were fairly numerous rather immature glomeruli but only a few normal tubules. The medullae were composed" of loose mature mesenchymal tissue and blood vessels with only a few cystically dilated tubules lined by cuboidal or flattened epithelium. Scattered throughout the kidneys were small loci of haemopoietic tissue. The liver showed extensive fatty change with nearly all the liver cells containing small or medium-sized fat droplets. In 1Department of Chemical Pathology,

Organic acids in aqueous humour and plasma: Post mortem study in infants and diagnosis of enzymopathies

“…But methylmalonic acid was present in the aqueous humour of three patients and its presence allowed the retrospective diagnosis of the disease (Coude et aI., 1989). The concentration of 2-hydroxyisovaleric acid (a catabolite of valine that is itself one of the precursors of propionic acid and so of methylmalonic acid) was increased in aqueous humour as in plasma of patient B. Aquous humour has previously been reported as a suitable material for the diagnosis of glutaric acidaemia type II (Bennett et aL, 1987) and methylmalonic acidaemia (Coude et al, 1989). The suitability of this fluid for the diagnosis of methylmalonic acidaemia and a complex fatty-acid oxidation disorder was confirmed.…”

Prenatal and foetal autopsy findings in glutaric aciduria type II

“…Once born, there are some signs that should draw our attention such as poor feeding, vomiting, dehydration, hypotonia (Bennett et al, 1984; Bennett, Pollitt, Land, Turner, & Cheetham, 1987; Colevas et al, 1988; Coude et al, 1981; Distelmaier et al, 2007; Domizio et al, 2005; S I Goodman, McCabe, Fennessey, & Mace, 1980; Stephen I. Goodman et al, 1982; Stephen I. Goodman, Reale, & Berlow, 1983; Hackl et al, 2017; Harkin, Gill, & Shapira, 1986; Kamiya et al, 1990; Slukvin et al, 2002; Stöckler, Radner, Karpf, Hauer, & Ebner, 1994; Sweetman, Nyhan, Tauner, Merritt, & Singh, 1980; Wilson et al, 1989), lethargy, tachypnoea/hyperpnoea, seizures. These symptoms are quite unspecific, so an infection should always be ruled out as sepsis can show the same symptomatology (Naga, 2015).…”

Disorders of mitochondrial β‐oxidation: Prenatal and early postnatal diagnosis and their relevance to Reye's syndrome and sudden infant death

“…This may be a particularly useful investigation where urine is not available, for example in cases of sudden death. Eye-fluid, which is often collected routinely during paediatric post-mortem examination, has been used to diagnose glutaric aciduria type II (Bennett et at,, 1987a) but there is no information at present whether it would reflect the more rapidly-evolving abnormalities of medium or long-chain acyl-CoA dehydrogenase deficiency, for example.…”