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In this work, NMR investigations that led to the discovery of a new inborn error of metabolism, beta-ureidopropionase (UP) deficiency, are reported. 1D (1)H-NMR experiments were performed using a patient's urine. 3-Ureidopropionic acid was observed in elevated concentrations in the urine spectrum. A 1D (1)H-(1)H total correlation spectroscopy (TOCSY) and two heteronuclear 2D NMR techniques (heteronuclear multiple bond correlation (HMBC) and heteronuclear single-quantum correlation (HSQC)) were used to identify the molecular structure of the compound that caused an unknown doublet resonance at 1.13 ppm. Combining the information from the various NMR spectra, this resonance could be assigned to 3-ureidoisobutyric acid. These observations suggested a deficiency of UP. With 1D (1)H-NMR spectroscopy, UP deficiency can be easily diagnosed. The (1)H-NMR spectrum can also be used to diagnose patients suffering from other inborn errors of metabolism in the pyrimidine degradation pathway.

Hydrocephalus internus (HCI) of all four ventricles in association with early neurological abnormalities is described as the presenting symptom in two patients with 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency. Decreased activity of MTHFR leads to reduction of 5-methyltetrahydrofolate, the main methyl donor for methionine synthesis necessary for synthesis of S-adenosyl-methionine (SAM). Demyelination in MTHFR deficiency has been attributed to low SAM levels in the brain. The biochemical hallmarks of the disorder are hyperhomocystinemia, homocystinuria and low levels of plasma methionine. Hydrocephalus internus requiring neurosurgical intervention has to our knowledge not been reported as a presenting feature of homocystinuria due to deficiency of MTHFR so far. The surprising finding of HCI of all four ventricles in MTHFR deficiency must be kept in mind when evaluating patients with hydrocephalus of unknown origin.

In this work, NMR investigations that led to the discovery of a new inborn error of metabolism, ␤-ureidopropionase (UP) deficiency, are reported. 1D 1 H-NMR experiments were performed using a patient's urine. 3-Ureidopropionic acid was observed in elevated concentrations in the urine spectrum. A 1D 1 H-1 H total correlation spectroscopy (TOCSY) and two heteronuclear 2D NMR techniques (heteronuclear multiple bond correlation (HMBC) and heteronuclear single-quantum correlation (HSQC)) were used to identify the molecular structure of the compound that caused an unknown doublet resonance at 1.13 ppm. Combining the information from the various NMR spectra, this resonance could be assigned to 3-ureidoisobutyric acid. These observations suggested a deficiency of UP. With 1D 1 H-NMR spectroscopy, UP deficiency can be easily diagnosed. The 1 H-NMR spectrum can also be used to diagnose patients suffering from other inborn errors of metabolism in the pyrimidine degradation pathway.

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Two sisters born to consanguineous Lebanese parents had mental retardation and epilepsy, brachymetacarpalia, hirsutism, bulbous soft nose, thick floppy ears with abnormal configuration and gingival hypertrophy. One girl presented additionally with tetralogy of Fallot and the other with congenital hypothyroidism and bilateral ureteral stenosis. These manifestations resemble the syndrome of hypertrichosis-gingival fibromatosis-mental retardation and seizures of Anavi et al. [1989: Dev Med Child Neurol 31:538-542] but our two girls additionally have brachymetacarpia. The inheritance seems to be autosomal recessive. These two sisters may represent a hitherto undescribed syndrome. We discuss the findings in our patients in relation to the literature.