Ketothiolase deficiency

Tiglylglycine C5 l ILE Propionic acidemia Methylmalonic acidemias Ketothiolase deficiency... 

Fig. 3.2.5 Profiles of acylcarnitines as their butyl esters in plasma (precursor of m/z 85 scan) of a normal control (a) and patients with various organic acidemias. Propionylcarnitine (C> m/z 274 peak 3) is the primary marker for both propionic acidemia (b) and methylmalonic acidemias (c). Note that an elevation of methylmalonylcarnitine (C4-UC m/z 374) is not typically found in patients with methylmalonic acidemias. In the three cases of ethylmalonic encephalopathy (d) analyzed in our laboratory, elevations of ,- (m/z 288 peak 4) and C5-acylcarnitine (m/z 302 peak 5) species were noted. Isolated C5-acylcarnitine elevations are encountered in patients with isovaleric acidemia (e), where it represents isovalerylcarnitine. Cs-Acylcarnitine is also elevated in patients with short/branched chain acyl-CoA dehydrogenase deficiency, where it represents 2-methylbutyrylcarnitine (see Fig. 3.2.4), and in patients treated with antibiotics that contain pivalic acid, where it represents pivaloylcarnitine [20, 59, 60]. Patients with /3-ketothio-lase deficiency (f) present with elevations of tiglylcarnitine (C5 i m/z 300 peak 6) and C5-OH acylcarnitine (m/z 318 peak 7). In most cases of 3-methylcrotonyl-CoA carboxylase deficiency (g) Cs-OH acylcarnitine is the only abnormal acylcarnitine species present. The differential diagnosis of C5-OH acylcarnitine elevations includes eight different conditions (Table 3.2.1). Also note that C5-OH acylcarnitine represents 3-hydroxy isovalerylcarnitine in 3-methylcrotonyl-CoA carboxylase deficiency (g), and 2-methyl 3-hydroxy butyrylcarnitine in / -ketothiolase deficiency...

Ozand PT, et al. 3-ketothiolase deficiency a review and four new patients with neurologic symptoms. Brain Dev. 1994 16(Suppl) 38-45. 

Fukao T, et al. Molecular basis of beta-ketothiolase deficiency mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene. Hum Mutat. 1995 5(2) 113-20. 

Succinyl-CoA 3-oxoacid-CoA-transferase deficiency (SCOT, 14.13) was already described in the early seventies. More than 10 patients are known now they all had multiple episodes of severe ketoacidosis, similar to the patients with jff-ketothiolase deficiency (see Sect. 7.4). Whenever there is hypoglycemia, this is denoted hyperketotic. Urine organic acids and plasma acylcarnitines are non-informative. Various mutations have been reported [17]. Growth and development of the patients was reported to be normal. 

Peroxisomal 3-ketothiolase deficiency (pseudo-Zellweger syndrome) Peroxisomal thiolase 1 (pThl) Generalized 3p23-p22 261510... 

Methylacetoacetic with 2-methyl-3-hydroxybutyric ()8-ketothiolase deficiency) (+) (+)... 

Hillman, R.E. and Keating, J.P. (1974), jS-Ketothiolase deficiency as a cause of the Ketotic hyperglycinemia syndrome . Pediatrics, 53,221. 

A sixth case, occurring in a 15-year-old boy, was reported by Halvorsen etal. (1979). Their patient, who was the second son of unrelated parents, had a history of coma and/or acidosis with ketonuria between 1 and 4 years of age, developing later in childhood episodes headaches, but with normal physical and mental development to 15 years of age. Large quantitities of 3-hydroxy-butyrate, 2-methyl-3-hydroxybutyrate and tiglylglycine were found in his urine together with increased amounts of adipic acid. No methylacetoacetate or acetoacetate were observed. A probable partial deficiency of )8-ketothiolase was postulated. 

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