Four cases of tyrosinaemia with cutaneous manifestations, but without ocular involvement, are reported in a family with consanguineous parents. The tyrosine levels in the serum and in the urine were normal in both parents, while in the offsprings the tyrosine levels were elevated 7 1/2-13 times in the serum and 3-13 times in the urine. Although the serum tyrosine levels in our cases were higher than most of the cases reported in the literature the eyes of all our patients were normal. The skin manifestations were very impressive, and varying degrees of mental retardation were present in all patients. The patients put on a low-protein diet improved considerably and have been kept symptom-free for 1 1/2 years. The possible implication of the discrepancy between the high serum levels and lack of ocular changes is discussed. Our results suggest that the Richner-Hanhart syndrome may include more than one distinct biochemical entity.

We present a summary of the results of quantitative amino acid analysis in 800 subjects over a three-year period in Al-Sabah Hospital, Kuwait. Thirty-five patients with aminoacidopathy were identified, all but two of whom were the offspring of first-degree consanguineous marriages: nine cases of phenylketonuria, one benign hyperphenylalaninaemia, seven non-ketotic hyperglycinaemia, five tyrosinaemia, five homocystinuria, four citrullinaemia, two cystinuria, one hyperprolinaemia, and one maple syrup urine disease. The clinical and biochemical findings in these cases are described.

Serum levels of breast carcinoma antigen (CA 15.3) and urinary calcium excretion (UCa) were determined in 73 patients with breast cancer: 36 without bone metastases (stage I-IV) and 37 with bone metastases. The patients in the latter group were further investigated at 2, 4 and 6 months from the start of treatment. Both markers showed significant elevations in the group with bone metastases (CA 15.3: P = 1.0 x 10(-6), UCa: P = 8.6 x 10(-9)). The bone metastasis index (BMI), which represents the combination of the markers, had better diagnostic efficacy (90%) than CA 15.3 alone (84%) or UCa alone (82%). During treatment of bone metastasis, the longitudinal levels of the markers showed a highly significant association with the therapeutic response assessed by the UICC criteria. For identifying progression of disease, the diagnostic efficacy of CA 15.3, UCa and a combination of both, the so-called Biochemical Index of Response (BIR), was 65%, 70% and 79%, respectively, at two months and 89%, 84% and 92% at four months. Application of the tandem, CA 15.3 with UCa, was very useful for the detection of bone metastases and the prediction of response to therapy.

Kuwait is a small Arabian Gulf country with a high rate of consanguinity and where a national newborn screening program was expanded in October 2014 to include a wide range of endocrine and metabolic disorders. A retrospective study conducted between January 2015 and December 2020 revealed a total of 304,086 newborns have been screened in Kuwait. Six newborns were diagnosed with classic homocystinuria with an incidence of 1:50,000, which is not as high as in Qatar but higher than the global incidence. Molecular testing for five of them has revealed three previously reported pathogenic variants in the CBS gene, c.969G>A, p.(Trp323Ter); c.982G>A, p.(Asp328Asn); and the Qatari founder variant c.1006C>T, p.(Arg336Cys). This is the first study to review the screening of newborns in Kuwait for classic homocystinuria, starting with the detection of elevated blood methionine and providing a follow-up strategy for positive results, including plasma total homocysteine and amino acid analyses. Further, we have demonstrated an increase in the specificity of the current newborn screening test for classic homocystinuria by including the methionine to phenylalanine ratio along with the elevated methionine blood levels in first-tier testing. Here, we provide evidence that the newborn screening in Kuwait has led to the early detection of classic homocystinuria cases and enabled the affected individuals to lead active and productive lives.

Objective: To report the importance of a rare organic acid metabolic disorder, L-2-hydroxyglutaric aciduria, and its characteristic neuroimaging cerebral white matter abnormalities in a case of epilepsy. Subject and Methods: A 19-year-old male presented with an 11-year history consisting of school failures, intellectual deterioration and generalized tonic-clonic convulsions. Results: Neurological examination showed mental subnormality, mild dysarthria and bilateral pyramidal signs. Computed tomography and magnetic resonance imaging (MRI) of the brain showed characteristic white matter lesions, suggestive of L-2-hydroxyglutaric aciduria. The diagnosis of this disease was confirmed by elevated urinary concentrations of L-2-hydroxyglutaric acid. The epilepsy was partially controlled with antiepileptic drugs. Conclusion: This report indicates the importance of routine examination of urinary organic acids in children and young adults presenting with chronic encephalopathy and epilepsy with characteristic MRI white matter lesions. L-2-hydroxyglutaric aciduria should be considered as one of the differential diagnoses of epilepsy.