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For GSD-Ia, hyperuricemia and pyelonephritis should be treated to prevent nephrocalcinosis and additional renal damage. For GSD-Ib, granulocyte-colony-stimulating factor may prevent bacterial infections. For GSD-III, more data are required to determine whether the myopathy and cardiomyopathy can be prevented. Most of the patients with GSD-I and GSD-III had 12 or more years of education and were either currently in school or employed.

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is a rare multisystem disorder characterized by extensive intracranial calcifications and cysts, leukoencephalopathy, and retinal vascular abnormalities. Additional features include poor growth, skeletal and hematological abnormalities, and recurrent gastrointestinal bleedings. Autosomal-recessive inheritance has been postulated. The pathogenesis of CRMCC is unknown, but its phenotype has key similarities with Revesz syndrome, which is caused by mutations in TINF2, a gene encoding a member of the telomere protecting shelterin complex. After a whole-exome sequencing approach in four unrelated individuals with CRMCC, we observed four recessively inherited compound heterozygous mutations in CTC1, which encodes the CTS telomere maintenance complex component 1. Sanger sequencing revealed seven more compound heterozygous mutations in eight more unrelated affected individuals. Two individuals who displayed late-onset cerebral findings, a normal fundus appearance, and no systemic findings did not have CTC1 mutations, implying that systemic findings are an important indication for CTC1 sequencing. Of the 11 mutations identified, four were missense, one was nonsense, two resulted in in-frame amino acid deletions, and four were short frameshift-creating deletions. All but two affected individuals were compound heterozygous for a missense mutation and a frameshift or nonsense mutation. No individuals with two frameshift or nonsense mutations were identified, which implies that severe disturbance of CTC1 function from both alleles might not be compatible with survival. Our preliminary functional experiments did not show evidence of severely affected telomere integrity in the affected individuals. Therefore, determining the underlying pathomechanisms associated with deficient CTC1 function will require further studies.

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A progressive neurologic syndrome developed in six children with longstanding cholestatic liver disease. The neurologic abnormalities included areflexia, gait disturbance, decreased proprioceptive and vibratory sensation, and paresis of gaze. Serum vitamin E concentrations were uniformly low. Neuropathological studies carried out in two of the three fatal cases revealed degeneration of the posterior column, selective loss of large-caliber, myelinated axons in peripheral nerve, and spheroids in the gracile and cuneate nuclei. These lesions are similar to those found in animals with experimentally induced vitamin E deficiency. We therefore speculate that the neurologic syndrome in these children may be the result of chronic vitamin E malabsorption.