Dicarboxylicaciduria and secondary carnitine deficiency in glycogenosis type IV

A 3 year old boy developed an unusually mild form of glycogen storage disease type IV. Metabolic investigations showed severe abnormalities of fatty acid and carnitine metabolism. A muscle carnitine deficiency was found. Treatment with L-carnitine orally led to a notable improvement in muscle strengt

Oculoauriculovertebral spectrum and cerebral anomalies.

We report on three Dutch children with a clinical diagnosis of oculoauriculovertebral spectrum (OAVS) and hydrocephalus. The clinical features are compared to 15 published cases of OAVS and hydrocephalus. Several other cerebral abnormalities were present in the whole group. About half of the cases had cleft lip/palate, anophthalmia/microphthalmia, or a cardiac defect. Mental retardation was found in five of the surviving 11 patients and early death occurred in one-third. We compared the cases with OAVS and hydrocephalus with published reports of OAVS and other cerebral anomalies and found no significant clinical differences. However, the clinical characteristics were clearly more severely expressed than generally found in patients with OAVS. Children with OAVS and more severe clinical features, especially anophthalmia/microphthalmia and cleft lip/palate, seem to be at an increased risk for cerebral malformations and for mental retardation

Molecular analysis of SALL1 mutations in Townes-Brocks syndrome.

Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome characterized by anal, renal, limb, and ear anomalies. Recently, we showed that mutations in the putative zinc finger transcription factor gene SALL1 cause TBS. To determine the spectrum of SALL1 mutations and to investigate the genotype-phenotype correlations in TBS, we examined 23 additional families with TBS or similar phenotypes for SALL1 mutations. In 9 of these families mutations were identified. None of the mutations has previously been described. Two of these mutations are nonsense mutations, one of which occurred in three unrelated families. Five of the mutations are short deletions. All of the mutations are located 5' of the first double zinc finger (DZF) encoding region and are therefore predicted to result in putative prematurely terminated proteins lacking all DZF domains. This suggests that only SALL1 mutations that remove the DZF domains result in TBS. We also present evidence that in rare cases SALL1 mutations can lead to phenotypes similar to Goldenhar syndrome. However, phenotypic differences in TBS do not seem to depend on the site of mutation