Fumaric aciduria: mild phenotype in a 8-year-old girl with novel mutations.

Fumaric aciduria is a rare, autosomal recessive disorder caused by deficient activity of fumarate hydratase (FH). Common clinical features are hypotonia, failure to thrive, severe psychomotor retardation and seizures. Facial dysmorphism and brain malformations are frequent. Recently, some FH gene mutations have been associated with inherited cutaneous and uterine leiomyomas and papillary renal cell cancer. Our patient had a relatively mild phenotype, a previously not reported genotype and familial tumour predisposition. The mother and grandmother had uterine myomas. The paternal grandfather and his two brothers died from lung and laryngeal cancers. The pregnancy was complicated by bleeding and intrauterine growth retardation. Delivery was after 35 weeks, with normal Apgar score. The girl was hypotonic since birth. At age 2 months the parents noticed short apnoeic crises. She could sit at age 1.5 years, and walk with assistance at 4 years. At age 8 years highly increased excretion of fumaric acid was found twice (217 and 445 mmol/mol creatinine). Shortly before that the girl started to have leg and arm spasms. Grand mal seizures occurred twice. Facial dysmorphism included depressed nasal bridge, anteverted ears, hypertelorism and microcephaly. Speech was limited to few disyllables. She was atactic with spastic paraparesis. Brain MRI showed slight ventriculomegaly, white-matter atrophy and hypoplasia of corpus callosum. Activity of FH in fibroblasts was 1.9 nmol/min/mg protein (controls 40-80). Analysis of the FH gene revealed the maternally derived c.1029_1031delAGT mutation, resulting in Val deletion and substitution of Gln by His, and paternally derived c.976C > T mutation, resulting in substitution of Pro by Ser.

S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger brother of the index patient, and outcomes during therapy.

S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency has been proven in a human only once, in a recently described Croatian boy. Here we report the clinical course and biochemical abnormalities of the younger brother of this proband. This younger brother has the same two mutations in the gene encoding AdoHcy hydrolase, and has been monitored since birth. We report, as well, outcomes during therapy for both patients. The information obtained suggests that the disease starts in utero and is characterized primarily by neuromuscular symptomatology (hypotonia, sluggishness, psychomotor delay, absent tendon reflexes, delayed myelination). The laboratory abnormalities are markedly increased creatine kinase and elevated aminotransferases, as well as specific amino acid aberrations that pinpoint the aetiology. The latter include, most importantly, markedly elevated plasma AdoHcy. Plasma S-adenosylmethionine (AdoMet) is also elevated, as is methionine (although the hypermethioninaemia may be absent or nonsignificant in the first weeks of life). The disease seems to be at least to some extent treatable, as shown by improved myelination and psychomotor development during dietary methionine restriction and supplementation with creatine and phosphatidylcholine.

The content of total fatty acids in the serum of healthy children from the Zagreb area.

A study of the fatty acid content was performed by gas chromatography in the sera of 26 healthy children aged 3-13 years and in the sera of 7 children aged up to three years, both from the Zagreb area. The following parameters were calculated for each subject and each fatty acid individually: mmol/l, mol%, g/l, mass% and mean molecular mass. On the basis of the results, the values of the parameters for the whole group of subjects were calculated. The values of these parameters for some characteristic groups of fatty acids (saturated, unsaturated, monounsaturated and long-chain polyunsaturated fatty acids) were also calculated and their interrelationship is presented. The ratio of fatty acids according to age groups (0-1, 1-3 and 3-13 years) is also shown. Fatty acids C 18:2, C 16:0 and C 18:1 with 32.87 mol%, 22.56 mol% and 20.79 mol%, respectively, were most frequently observed in the children's sera, which correlated well with the generally known data. Essential fatty acids were present in the following amounts: C 20:4, 5.49 mol%; C 22:5, 0.26 mol%; and C 22:6, 0.82 mol%. The sera of the children aged up to one year were found to contain significantly higher amounts of short-chain fatty acids and lower amounts of C 18:2 and C 20:4 than the sera from children older than one year.